ABSTRACT: BACKGROUND: Recent advances in whole-genome association studies (WGASs) for human cancer risk are beginning to provide the part lists of low-penetrance susceptibility genes. However, statistical analysis in these studies is complicated by the vast number of genetic variants examined and the weak effects observed, as a result of which constraints must be incorporated into the study design and analytical approach. In this scenario, biological attributes beyond the adjusted statistics generally receive little attention and, more importantly, the fundamental biological characteristics of low-penetrance susceptibility genes have yet to be determined. METHODS: We applied an integrative approach for identifying candidate low-penetrance breast cancer susceptibility genes, their characteristics and molecular networks through the analysis of diverse sources of biological evidence. RESULTS: First, examination of the distribution of Gene Ontology terms in ordered WGAS results identified ...
Genetic predisposition to obesity is no barrier to successful weight management The benefits of sticking to a healthy diet to prevent long term weight gain are greater in people at high genetic risk for obesity than in those with low genetic risk, finds a study in The BMJ today. The researchers say their findings
TY - JOUR. T1 - Breast cancer risk and 6q22.33. T2 - combined results from Breast Cancer Association Consortium and Consortium of Investigators on Modifiers of BRCA1/2. AU - Kirchhoff, Tomas. AU - Gaudet, Mia M. AU - Antoniou, Antonis C. AU - McGuffog, Lesley. AU - Humphreys, Manjeet K. AU - Dunning, Alison M. AU - Bojesen, Stig E. AU - Nordestgaard, Børge G. AU - Flyger, Henrik. AU - Kang, Daehee. AU - Yoo, Keun-Young. AU - Noh, Dong-Young. AU - Ahn, Sei-Hyun. AU - Dork, Thilo. AU - Schürmann, Peter. AU - Karstens, Johann H. AU - Hillemanns, Peter. AU - Couch, Fergus J. AU - Olson, Janet. AU - Vachon, Celine. AU - Wang, Xianshu. AU - Cox, Angela. AU - Brock, Ian. AU - Elliott, Graeme. AU - Reed, Malcolm W R. AU - Burwinkel, Barbara. AU - Meindl, Alfons. AU - Brauch, Hiltrud. AU - Hamann, Ute. AU - Ko, Yon-Dschun. AU - GENICA Network. AU - Broeks, Annegien. AU - Schmidt, Marjanka K. AU - Van t Veer, Laura J. AU - Braaf, Linde M. AU - Johnson, Nichola. AU - Fletcher, Olivia. AU - Gibson, ...
The National Cancer Institute (NCI), part of the National Institutes of Health, has released new data from the Cancer Genetic Markers of Susceptibility (CGEMS) study on prostate cancer. This information could help identify genetic factors that influence the disease and will be integral to the discovery and development of new, targeted therapies. This is also the first public release of a whole genome association study of cancer -- such studies examine the entire genome, with no assumptions about which genetic alterations cause cancer. Knowing which genes are most likely to lead to cancer will greatly enhance our ability to diagnosis the disease at its earliest stages, as well as develop therapies to treat cancer when it is most vulnerable to attack, said NCI Director John E. Niederhuber, M.D. Launched in February 2006, CGEMS is the largest comprehensive initiative to identify genetic risk factors for breast and prostate cancers, which are two of the most frequently diagnosed cancers in the ...
At what age should preventive examinations be started with a hereditary predisposition to cancer? The head of the oncology department of MONICA, doctor Alexander Allahverdyan, claims that information about close relatives who have developed cancer diseases can help to figure this out.. Ten years should be taken away from the age of death of a relative who had cancer. It is during this period that regular examinations should begin. If, for example, the father died of cancer at the age of 56, a person needs to start an examination every year after 46 years, he said ...
Background:Crohns disease (CD) is an intractable inflammatory bowel disease of unknown cause. Recent genome-wide association studies of CD in Korean and Japanese populations suggested marginal sharing of susceptibility loci between Caucasian and Asian populations. As the 7 identified loci altogethe
Results An association between SNP rs3802842 on chromosome 11q23.1 and rs16892766 on chromosome 8q23.3 and the risk of developing CRC and age of diagnosis was found in MLH1 mutation carriers. Female MLH1 mutation carriers harbouring the homozygous variant genotype for SNP rs3802842 have the highest risk of developing CRC. When the number of risk alleles for the two SNPs combined was analysed, a difference of 24 years was detected between individuals carrying three risk alleles and those carrying no risk alleles. ...
Recent advances in human genome studies have opened new avenues for the identification of susceptibility genes for many complex genetic disorders, especially in the field of rare cancers such as glioma. To date, eight glioma susceptibility loci have been identified by candidate gene-association studies: PRKDC G6721T, XRCC1 W399R, PARP1 A762V, MGMT F84L, ERCC1 A8092C, ERCC2 Q751K, EGF +61 A/G, and IL13 R110G. Five loci have been identified by genome-wide association studies: TERT rs2736100, CCDC26 rs4295627, CDKN2A-CDKN2B rs4977756, PHLDB1 rs498872, and RTEL1 rs6010620. Using the Ingenuity Pathway Analysis tool, we investigated whether these 13 susceptibility genes are biologically related. Our data provide not only networks for understanding the biological properties of gliomagenesis but also useful pathway maps for future understanding of disease.. ...
It is now recognised that a part of the inherited risk of colorectal cancer (CRC) can be explained by the co-inheritance of low-penetrance genetic variants. The accumulated experience to date in identifying these variants has served to highlight difficulties in conducting statistically and methodologically rigorous studies and follow-up analyses. The COGENT (COlorectal cancer GENeTics) consortium includes 20 research groups in Europe, Australia, the Americas, China and Japan. The overarching goal of COGENT is to identify and characterise low-penetrance susceptibility variants for CRC through association-based analyses. In this study, we review the rationale for identifying low-penetrance variants for CRC and our proposed strategy for establishing COGENT.
Several lines of evidence exist that lend support to T790M as a putative susceptibility allele. T790M has been detected somatically in tumors that have not been treated with gefitinib or erlotinib, which may suggest that this mutant may have arisen during drug-free cancer progression ( 15). Furthermore, the NCI-H1975 BAC cell line, which has never undergone tyrosine kinase inhibitor treatment, has both activating L858R and resistant T790M mutations, suggestive that T790M may be growth promoting ( 5). Bell et al. ( 8) also have observed that the T790M mutation seems to occur in cis with the activating mutations. Perhaps more persuasive is that the analogous resistance mutation in CML patients, BCR-ABL-T315I, displays increased in vitro kinase activity ( 16). Similarly, the analogous mutations in Src (T341M) and FGFR1 (V561M) also result in increased phosphorylation and activation ( 10). Why T790M in EGFR does not reportedly function in a similar manner is unclear.. Our results suggest that the ...
OUTLINE: Patients undergo transvaginal ultrasonography of the ovaries (scheduled for the early follicular phase, day 3-6 of the menstrual cycle) and CA 125 measurement annually. Blood samples are collected every 4 months for analysis of CA 125 levels and novel markers.. Peer Reviewed and Funded or Endorsed by Cancer Research UK. PROJECTED ACCRUAL: A total of 5,000 patients will be accrued for this study. ...
Host genetic variation in components of both specific and innate immune responses affects susceptibility to viral infections. Innate immunity provides the first line of defense, and the development of adaptive immunity is stimulated by innate responses. Pathogen recognition receptors (PRRs) initiate signaling pathways that result in the production of antiviral interferons and cytokines. Mutations or genetic variants (polymorphisms) have been recognized in several factors of innate immunity. Notably, human populations from distinct geographic areas have different frequencies of immune gene variants. The genetic susceptibility may vary from life-threatening manifestations of specific virus infections to a moderately increased frequency of nonsevere infections. Although the innate immunity is nonspecific by nature, the reactions are stereotypic for viral infections compared with bacterial infections. Even infections caused by specific viruses can be differentiated from each other based on the innate immune
Attempting to classify patients into high or low risk for disease onset or outcomes is one of the cornerstones of epidemiology. For some (but by no means all) diseases, clinically usable risk prediction can be performed using classical risk factors such as body mass index, lipid levels, smoking status, family history and, under certain circumstances, genetics (e.g. BRCA1/2 in breast cancer). The advent of genome-wide association studies (GWAS) has led to the discovery of common risk loci for the majority of common diseases. These discoveries raise the possibility of using these variants for risk prediction in a clinical setting. We discuss the different ways in which the predictive accuracy of these loci can be measured, and survey the predictive accuracy of GWAS variants for 18 common diseases. We show that predictive accuracy from genetic models varies greatly across diseases, but that the range is similar to that of non-genetic risk-prediction models. We discuss what factors drive differences in
TY - JOUR. T1 - Fine mapping of type 1 diabetes susceptibility loci and evidence for colocalization of causal variants with lymphoid gene enhancers. AU - Onengut-Gumuscu, Suna. AU - Chen, Wei Min. AU - Burren, Oliver. AU - Cooper, Nick J.. AU - Quinlan, Aaron R.. AU - Mychaleckyj, Josyf C.. AU - Farber, Emily. AU - Bonnie, Jessica K.. AU - Szpak, Michal. AU - Schofield, Ellen. AU - Achuthan, Premanand. AU - Guo, Hui. AU - Fortune, Mary D.. AU - Stevens, Helen. AU - Walker, Neil M.. AU - Ward, Lucas D.. AU - Kundaje, Anshul. AU - Kellis, Manolis. AU - Daly, Mark J.. AU - Barrett, Jeffrey C.. AU - Cooper, Jason D.. AU - Deloukas, Panos. AU - Todd, John A.. AU - Wallace, Chris. AU - Concannon, Patrick. AU - Rich, Stephen S.. AU - Baskerville, Tracey. AU - Bautista, Nines. AU - Bhatia, Eesh. AU - Bhatia, Vijayalakshmi. AU - Hasan, Kamaruzaman Bin. AU - Bonnici, Francois. AU - Brodnicki, Thomas. AU - Browning, Brian. AU - Cameron, Fergus. AU - Chaichanwatanakul, Katharee. AU - Cheung, Pik To. AU - ...
In mammalian cells the accumulation of repair proteins to double-strand breaks is a phosphorylation- and ubiquitylation-regulated process. Some of the genes that encode the kinases and ubiquitin ligases in this pathway are cancer predisposition genes, most prominently the breast cancer predisposition gene BRCA1, which encodes a ubiquitin ligase. How BRCA1 ligase activity was regulated following DNA damage was poorly understood. In this review I summarize new data that show a third post-translational modification, by the small ubiquitin like modifier SUMO, is part of the same cascade, enabling and activating DNA damage-regulated processes, including the BRCA1 ligase activity. Cancer Res; 70(10); OF1-3. ©2010 AACR. ...
Recent dramatic advances in the understanding of inherited susceptibility to several common adult-onset cancers have made possible the identification of individuals who may be at significantly increased risk of developing malignant disease. These advances may translate into some of the first opportunities for cancer prevention.
Genetic predisposition in simple terms means an individual possessing a genetic characteristic which is likely to express itself as an ailment due to an environment trigger. This means even though a human being is NOT born with a disorder, he/she has high chances of acquiring it in future. As per the best nutritionist in Mumbai this is also termed as genetic susceptibility. It is majorly categorized as a Non-Communicable Disease by the World Health Organization. Identifying the triggers for genetic predisposition Understanding genetic predisposition is directly linked with informed choices as well as individual lifestyle. Nutritional status forms the maximum of it. Here is a list of ailments which are more likely to occur due to the genetic makeup of an individual: ...
My laboratory focuses on understanding the genetic architecture of autism. We are working with genome-wide genetic data to identify additional susceptibility loci, the genetic mechanisms by which DNA variants influence autism risk, and the genetic and physiological pathways these risk loci implicate. We can use rich genetic datasets to ask questions about the role for copy number vs. SNP variation, rare vs. common variation, gene-sex interaction, gene-gene interaction, and gene-environment interaction.. We are also using human induced pluripotent stem cell (iPSC) models to study known mutations or copy number variants predisposing to autism. We will first identify the effects of genetic risk variants and then be able to ascertain whether the effects of genetic risk can be modified at the cellular level by environmental or pharmacological agents. These models will be used to test hypotheses emerging from our genetic datasets.. Our long term goals are to use genetic tools to improve understanding, ...
Using a range of experimental and bioinformatic procedures to overcome the barriers associated with the study of primary human GI T cells under homeostatic conditions, we report here unbiased expression microarray data for minimally manipulated T cells from the small intestine of tightly matched, healthy controls. We demonstrate that this approach allows the identification of genes upregulated in specific gut T cell subsets and that these genes cluster non-randomly around risk loci for inflammatory pathologies, thus providing an alternative novel approach to candidate gene identification at GWAS risk loci.. The only previously reported human intestinal T cell transcriptional studies used prolonged in vitro culture and expansion of clones derived from atypical IEL T cells associated with refractory CeD.46 ,47 Here, we used material from just eight ileal biopsies, allowing study of physiologically relevant tissue from healthy control individuals rather than dependence upon diseased explants. Low ...
Venous thromboembolism (VTE) is a multifactorial disorder involving both acquired and genetic risk factors. The common genetic factors in Western populations have been studied and reported for several decades, while studies on Asian populations are relatively scarce. Evidence suggests that the prevalence and genetic risk factors of VTE vary significantly among ethnic populations. In this review, we summarize the common genetic risk factors of VTE in both Western and Asian populations. ...
Background: Epidemiologic studies have reported a positive association between type 2 diabetes (T2D) and breast cancer risk, independent of body weight. Methods: We investigated 40 genetic variants known to be associated with T2D in relation to breast cancer risk among 2651 breast cancer cases and 2520 controls of African or European ancestry that were pooled from seven studies. Results: We found that two T2D risk alleles in Caucasian women (rs5945326-G, rs12518099-C) and one in women of African ancestry (rs7578597-T) were positively associated with breast cancer risk at a nominal significance level of 0.05, whereas two T2D risk alleles were inversely associated with breast cancer risk in Caucasian women (rs1111875-C, rs10923931-T). The composite T2D susceptibility score (the number of risk allele) was not significantly associated with breast cancer risk. Conclusion: The association between established T2D genetic susceptibility variants and breast cancer risk in women of African or European ...
Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis ...
Causes of pancreatic cancer include various known and unknown factors. The incidence of pancreatic cancer increases with age. African Americans tend to be more likely to acquire cancer of the pancreas. Cigarette smoking, recent onset diabetes, chronic pancreatitis, obesity, heavy drinking, and family genetics may be risk factors.
I refer all women diagnosed with a HGSC of the ovary, fallopian tube or the peritoneum, irrespective of age, to the Hereditary Cancer Program for genetic counseling and for BRCA mutation testing.
OBJECTIVE: The UCHL-1 gene is widely cited as a susceptibility factor for sporadic Parkinsons disease (PD). The strongest evidence comes from a meta-analysis of small studies that reported the S18Y polymorphism as protective against PD, after pooling studies of white and Asian subjects. Here, we present data that challenge this association. METHODS: In a new large case-control study in white individuals (3,023 subjects), the S18Y variant was not protective against PD under any genetic model of inheritance. Similarly, a more powerful haplotype-tagging approach did not detect other associated variants. RESULTS: Finally, in an updated S18Y-PD meta-analysis (6,594 subjects), no significant association was observed under additive, recessive, or dominant models (odds ratio = 1.00 [95% confidence interval: 0.74-1.33]; odds ratio = 1.01 [95% confidence interval: 0.76-1.35]; and odds ratio = 0.96 [95% confidence interval: 0.86-1.08], respectively), and a cumulative meta-analysis showed a trend toward a ...
The Liver Diseases Genetics and Genomics program supports research to identify genes that influence normal development, function, and diseases of the liver
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Although men of African ancestry have a high risk of prostate cancer (PCa), no genes or mutations have been identified that contribute to familial clustering of PCa in this population. We investigated whether the African ancestry-specific PCa risk variant at 8q24, rs72725854, is enriched in men with a PCa family history in 9052 cases, 143 cases from high-risk families, and 8595 controls of African ancestry. We found the risk allele to be significantly associated with earlier age at diagnosis, more aggressive disease, and enriched in men with a PCa family history (32% of high-risk familial cases carried the variant vs 23% of cases without a family history and 12% of controls). For cases with two or more first-degree relatives with PCa who had at least one family member diagnosed at age ,60 yr, the odds ratios for TA heterozygotes and TT homozygotes were 3.92 (95% confidence interval [CI] = 2.13-7.22) and 33.41 (95% CI = 10.86-102.84), respectively. Among men with a PCa family history, the ...
We have found a substantial number of reports of studies that have investigated candidate genes for low-penetrance breast cancer susceptibility alleles. Despite this research effort, there is no clear evidence that any of these polymorphisms are strongly associated with breast cancer risk. Of the individual studies, few of the reported associations have been statistically significant, and no significant association has been reported by more than one study. In some cases, this might be due to a lack of statistical power in individual studies. Even among the significant associations, the magnitude of the effect found is rarely greater than 2.5-fold increased risk. If the rare allele frequency is 0.2, 315 cases and 315 controls would be required to detect this magnitude of risk for a rare allele homozygote with 90% power at the 5% significance level: 10 of the 46 studies reported were larger than this.. We have attempted to reduce this lack of power by combining results in meta-analyses, but even ...
The expected results will provide a clear picture of the role of common low-susceptibility sequence variants compared to rare high- and intermediate-risk sequence variants, and will contribute to better knowledge of genetic susceptibility factors in BC risk. The results obtained will help to identify inpidual and combined role of genetic variants of the three tiers of genes/loci and their profile with different level of penetrance to BC. The calculated gPAF of each gene, common and rare variants will have potential benefit for BC targeted preventive intervention and early detection programs when considering genetic susceptibility burden in the population. The expecting results also will have commercial significance with a direct consequence to the public health, especially for the development of a genetic risk assessment program and a genetic test which in turn will have a huge impact to detect and reduce hereditary burden of BC in a specific population. The analysis of common low-susceptibility ...
Our data demonstrate that polymorphisms in the AKT2 gene are significantly associated with PCOS. The minor alleles of rs3730051 and rs8100018 were associated with PCOS, and the corresponding haplotype was also associated with PCOS. We used independent, additive, and combined logistic regression models to demonstrate that the association between AKT2 haplotype T-G-C-T and PCOS was independent of the GSK3B risk haplotype, but PCOS risk was increased when both were present. These data offer two potential susceptibility loci from the insulin signaling pathway that may confer increased PCOS risk and suggest that the presence of multiple lesions in a single pathway confers increased risk.. The significant association of rs3735001 and rs8100018 with PCOS extends to a haplotype that includes the minor alleles of these two AKT2 SNPs. Carriers of both minor alleles, in a haplotype, had the same OR as carriers of either risk allele alone, as a SNP. This finding suggests that these alleles are markers ...
Although the recent evidence for individual differences in plasticity is quite compelling, the authors are very tentative and cautious in their papers, which I suppose is necessary when youre proposing something new. You dont want to scare anyone off. So they are keen to point out that the evidence is not quite solid as yet, and there is more work to be done.. This line of work is only beginning, and there are many unknowns. Much the same as in priming research, the evidence of the effect is running a little ahead of the understanding of the mechanisms involved, and researchers are unclear on whether differential susceptibility stems mostly from nature or nurture, or on the breadth of the phenomena that it applies to. Having said that, the idea that that the people most susceptible to negative symptoms and experiences might be the people most susceptible to positive symptoms and experiences, is quite a cheerful thought.. References:. (1) Belsky, J., & Pluess, M. (2009). Beyond diathesis ...
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Online supplementary table 1 summarises terms used to describe sequence variants, and their association with or relevance to disease, and to patient clinical management. The information was derived from a combination of knowledge from the literature, usage in verbal and written project reporting across ENIGMA, in clinical reports generated or viewed by ENIGMA members and documentation/terms described by the Human Variome Project (HVP; http://www.humanvariomeproject.org), ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/) and International Society for Gastrointestinal Hereditary Tumours (InSiGHT; https://www.insight-group.org/). The content was presented to ENIGMA members at several consecutive consortium meetings, and also circulated in document form, to invite feedback and additions. While not claiming to be an exhaustive list of terms and their meanings, it is clear that a single term/phrase can be used to describe different aspects relating to a variant (different intent), and that multiple ...
Genetic Predisposition News. Find breaking news, commentary, and archival information about Genetic Predisposition From The tribunedigital-sunsentinel
The current explosion of GWAS, driven in part by falling genotyping costs, has revealed some causal variants and others that have failed to replicate. In some cases, the observed linkage of associated SNPs to coding genes suggests that the associated variant might alter risk by regulating gene expression. cis-linked noncoding sequences often contain consensus binding sites for transcription factors [ENCODE Project Consortium, 2007], and recently, a causal variant for colorectal cancer was shown to be a cis-eQTL for SMAD7 expression [Pittman et al., 2009], suggesting that other associated variants might alter disease predisposition by affecting expression levels of key signaling molecules. Although not all causal variants are likely to regulate expression levels of protein-coding genes, such evidence for an associated SNP can be useful information. Assuming that the associated variant somehow regulates the expression levels of a coding gene, existing prior biological
TY - JOUR. T1 - Investigating the viability of genetic screening/testing for RA susceptibility using combinations of five confirmed risk loci. AU - McClure, Annie. AU - Lunt, Mark. AU - Eyre, Steve. AU - Ke, Xiayi. AU - Thomson, Wendy. AU - Hinks, Anne. AU - Bowes, John. AU - Gibbons, Laura. AU - Plant, Darren. AU - Wilson, Anthony G. AU - Marinou, Ioanna. AU - Morgan, Ann W. AU - Emery, Paul. AU - Steer, Sophia. AU - Hocking, Lynne. AU - Reid, David M. AU - Wordsworth, Paul. AU - Harrison, Pille. AU - Worthington, Jane. AU - Barton, Anne. AU - BIRAC consortium. PY - 2009. Y1 - 2009. N2 - OBJECTIVE: Five loci-the shared epitope (SE) of HLA--DRB1, the PTPN22 gene, a locus on 6q23, the STAT4 gene and a locus mapping to the TRAF1/C5 genetic region--have now been unequivocally confirmed as conferring susceptibility to RA. The largest single effect is conferred by SE. We hypothesized that combinations of susceptibility alleles may increase risk over and above that of any individual locus alone. ...
Cancer incidence varies markedly by ethnicity and geographic location. Ethnic variation in cancer occurrence has traditionally been ascribed to differences in social, cultural, economic, and physical environments. However, this interpretation of the epidemiologic evidence may need to be revised as a result of new biological evidence and theories of carcinogenesis. Carcinogenesis is now recognized
Depression can be hereditary and some members will be at high genetic risk. But having a one of parents or very close relative with depression will not mean you will get it by default or get the same experience. Vastu imbalance and kundali or personal horoscope are still likely to have an important influence of depres
New Delhi, Nov 30 (IANS) The good news: Healthy behaviour appears to slash the risk of coronary disease in people at high genetic risk for events. The bad...
The discovery of inherited gene mutations that increase the risk of certain cancers could greatly expand the use of predictive genetic testing in healthy individuals. In families with hereditary forms of cancer, the use of genetic tests to determine whether family members have inherited suseptibility mutations (ISMs} may improve out come. 1
Genetic testing and counseling is available for patients at risk for breast, ovarian and colon cancer. BRCA1 and BRCA2 testing is available.
A woman who discovers she is at risk for developing breast cancer may wonder if someone else in her family is also at risk. That very thought can help save a life. An estimated 10 percent of women diagnosed with breast cancer have a hereditary predisposition to the disease and are at substantial risk for…
(HealthDay)-For patients with type 2 diabetes (T2D), having a genetic predisposition towards the disease is associated with an increased risk of cardiovascular disease (CVD), according to a study published online Oct. 15 ...
SwePub titelinformation: Identifying Novel Susceptibility Genes for Colorectal Cancer Risk From a Transcriptome-Wide Association Study of 125,478 Subjects
Kevin Light MD offers EstroGenomic Profile genetic testing for breast cancer, osteoporosis, and heart disease predispositions for clients at his Texas medical center
I was released from the hospital yesterday around noon. I was supposed to be in for at least a week but they let me go a day early. They are almost totally sure that it was a very acute heart attack caused by a blood clot in the coronary vessel. The blockage was so slight that it dissolved or dislodged itself due to the pressure. This is apparently quite common and happens in about 10% of heart attacks, many of which go unreported because they are not even recognized as being heart attacks. Still uncertain is where the blood clot came from and whether or not there is a high risk of it happening again. The doctor said it was not the result of a thrombosis caused by laying in bed for 3 days. Nor was it caused by any defects such as faulty valves or holes in the wall of the heart. It could be a hereditary predisposition as heart problems seem to run in the family. This lack of certainty is frustrating. Was it a one-time fluke? Could it happen easily again? Am I walking around with a time-bomb in my ...
Prostate cancer is the most frequently diagnosed cancer in males in developed countries. To identify common prostate cancer susceptibility alleles, we genotyped 211,155 SNPs on a custom Illumina array (iCOGS) in blood DNA from 25,074 prostate cancer cases and 24,272 controls from the international PRACTICAL Consortium. Twenty-three new prostate cancer susceptibility loci were identified at genome-wide significance (P | 5 × 10(-8)). More than 70 prostate cancer susceptibility loci, explaining ∼30% of the familial risk for this disease, have now been identified. On the basis of combined risks conferred by the new and previously known risk loci, the top 1% of the risk distribution has a 4.7-fold higher risk than the average of the population being profiled. These results will facilitate population risk stratification for clinical studies.
Montserrat Garcia-Closas and colleagues report a genome-wide association study for bladder cancer. They identify three new susceptibility loci on chromosomes 22q13.1, 19q12 and 2q37.1. We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10−12) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10−11) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10−7) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10
Genome-wide association studies (GWAS) of chronic lymphocytic leukemia (CLL) have shown that common genetic variation contributes to the heritable risk of CLL. To identify additional CLL susceptibility loci, we conducted a GWAS and performed a meta-analysis with a published GWAS totaling 1,739 individuals with CLL (cases) and 5,199 controls with validation in an additional 1,144 cases and 3,151 controls. A combined analysis identified new susceptibility loci mapping to 3q26.2 (rs10936599, P =...
TY - JOUR. T1 - Identification of a new prostate cancer susceptibility locus on chromosome 8q24. AU - Yeager, Meredith. AU - Chatterjee, Nilanjan. AU - Ciampa, Julia. AU - Jacobs, Kevin B.. AU - Gonzalez-Bosquet, Jesus. AU - Hayes, Richard B.. AU - Kraft, Peter. AU - Wacholder, Sholom. AU - Orr, Nick. AU - Berndt, Sonja. AU - Yu, Kai. AU - Hutchinson, Amy. AU - Wang, Zhaoming. AU - Amundadottir, Laufey. AU - Feigelson, Heather Spencer. AU - Thun, Michael J.. AU - Diver, W. Ryan. AU - Albanes, Demetrius. AU - Virtamo, Jarmo. AU - Weinstein, Stephanie. AU - Schumacher, Fredrick R.. AU - Cancel-Tassin, Geraldine. AU - Cussenot, Olivier. AU - Valeri, Antoine. AU - Andriole, Gerald L.. AU - Crawford, E. David. AU - Haiman, Christopher A.. AU - Henderson, Brian. AU - Kolonel, Laurence. AU - Le Marchand, Loic. AU - Siddiq, Afshan. AU - Riboli, Elio. AU - Key, Timothy J.. AU - Kaaks, Rudolf. AU - Isaacs, William. AU - Isaacs, Sarah. AU - Wiley, Kathleen E.. AU - Gronberg, Henrik. AU - Wiklund, ...
Uncovering common genetic risk factors for Parkinsons disease Introduction. Mutations in the so called PARK genes lead to rare familial forms of Parkinsons disease (PD). However the extent to which common genetic variability around these genes alters risk for common PD remains unclear. The Australian Parkinsons Project is analysing genetic variability around the PARK loci in a large PD case-control sample recruited from three Australian states. The emphasis is on gene-gene and gene-environment interactions between commonly occurring variables. Aim. To report on a pilot PD association analysis of 87 polymorphisms around13 PARK genes in an initial case-control sample recruited during 2006. Methods. PD cases (n=326) and unaffected control subjects (n=298) of white European ancestry were recruited from three specialist clinics in Brisbane and the Australian Electoral Roll. Common genetic variables (86 SNPs genotyped on the TaqMan platform and 1 STR variable genotyped using standard methods) were ...
Novel association of a functional single nucleotide polymorphism in the BTNL2 gene with susceptibility to rheumatoid arthritis and baseline radiographic severity in African-Americans independent of HLA DRB1: Results from the CLEAR registry ...
Breast Cancer Association Consortium (BCAC), Barretts and Esophageal Adenocarcinoma Consortium (BEACON), Colon Cancer Family Registry (CCFR), Transdisciplinary Studies of Genetic Variation in Colorectal Cancer (CORECT), Endometrial Cancer Association Consortium (ECAC), Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), Melanoma Genetics Consortium (GenoMEL), Glioma International Case-Control Study (GICC), International Lung Cancer Consortium (ILCCO), Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) Consortium, International Consortium of Investigators Working on Non-Hodgkins Lymphoma Epidemiologic Studies (InterLymph), Ovarian Cancer Association Consortium (OCAC), Oral Cancer GWAS, Pancreatic Cancer Case-Control Consortium (PanC4), Pancreatic Cancer Cohort Consortium (PanScan), Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL), Renal Cancer GWAS, Testicular Cancer Consortium (TECAC), Zhang, Y. D., Hurson, A. ...
The survival of breast cancer patients is largely influenced by tumor characteristics, such as TNM stage, tumor grade and hormone receptor status. However, there is growing evidence that inherited genetic variation might affect the disease prognosis and response to treatment. Several lines of evidence suggest that alleles influencing breast cancer risk might also be associated with breast cancer survival. We examined the associations between 35 breast cancer susceptibility loci and the disease over-all survival (OS) in 10,255 breast cancer patients from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3) of which 1,379 died, including 754 of breast cancer. We also conducted a meta-analysis of almost 35,000 patients and 5,000 deaths, combining results from BPC3 and the Breast Cancer Association Consortium (BCAC) and performed in silico analyses of SNPs with significant associations. In BPC3, the C allele of LSP1-rs3817198 was significantly associated with improved OS ...
Introduction Systemic Lupus Erythematosus (SLE) shows a spectrum of clinical manifestations that complicate its diagnosis, treatment and research. This variability is likely related with environmental exposures and genetic factors among which known SLE susceptibility loci are prime candidates. The first published analyses seem to indicate that this is the case for some of them, but results are still inconclusive and we aimed to further explore this question. Methods European SLE patients, 1444, recruited at 17 centres from 10 countries were analyzed. Genotypes for 26 SLE associated SNPs were compared between patients with and without each of 11 clinical features: ten of the American College of Rheumatology (ACR) classification criteria (except ANAs) and age of disease onset. These analyses were adjusted for centre of recruitment, top ancestry informative markers, gender and time of follow-up. Overlap of samples with previous studies was excluded for assessing replication. Results There were three
A recent genome-wide association study (GWAS) conducted by the International Multiple Sclerosis Genetics Consortium (IMSGC) identified a number of putative MS susceptibility genes. Here we have performed a replication study in 1134 Australian MS cases and 1265 controls for 17 risk-associated single nucleotide polymorphisms (SNPs) reported by the IMSGC. Of 16 SNPs that passed quality control filters, four, each corresponding to a different non-human leukocyte antigen (HLA) gene, were associated with disease susceptibility: KIAA0350 (rs6498169) P=0.001, IL2RA (rs2104286) P=0.033, RPL5 (rs6604026) P=0.041 and CD58 (rs12044852) P=0.042. There was no association (P=0.58) between rs6897932 in the IL7R gene and the risk of MS. No interactions were detected between the replicated IMSGC SNPs and HLA-DRB1*15, gender, disease course, disease progression or age-at-onset. We used a novel Bayesian approach to estimate the extent to which our data increased or decreased evidence for association with the six ...
Genome-wide association studies (GWASs) have identified a number of genetic risk loci associated with systemic sclerosis (SSc) and Crohns disease (CD), some of which confer susceptibility to both diseases. In order to identify new risk loci shared between these two immune-mediated disorders, we performed a cross-disease meta-analysis including GWAS data from 5,734 SSc patients, 4,588 CD patients and 14,568 controls of European origin. We identified 4 new loci shared between SSc and CD, IL12RB2, IRF1/SLC22A5, STAT3 and an intergenic locus at 6p21.31. Pleiotropic variants within these loci showed opposite allelic effects in the two analysed diseases and all of them showed a significant effect on gene expression. In addition, an enrichment in the IL-12 family and type I interferon signaling pathways was observed among the set of SSc-CD common genetic risk loci. In conclusion, through the first cross-disease meta-analysis of SSc and CD, we identified genetic variants with pleiotropic effects on two ...
The recognition that prostate cancer has a strong familial component has led to the search for prostate cancer susceptibility genes. Localization of these genes through linkage studies, however, has become a particularly formidable task. Prostate cancer is the most common cancer affecting American men; this high background rate of sporadic cancer obscures the ability to identify families with true genetic predisposition. Prostate cancer is also a late-onset disease. Thus, it is often difficult to identify and collect samples from individuals in several generations. Despite these problems, linkage studies have identified three autosomal putative prostate cancer susceptibility loci, namely, HPC1, PCAP, and CAPB. The likelihood of locus heterogeneity further complicates prostate cancer linkage studies and necessitates large sample sizes.. To localize HPCX, Xu et al. (16) studied 360 prostate cancer families with an average of 4.3 affected men/family obtained from research studies from two ...
Candidate gene and genome-wide association studies (GWAS) have identified 15 independent genomic regions associated with bladder cancer risk. In search for additional susceptibility variants, we followed up on four promising single-nucleotide polymorphisms (SNPs) that had not achieved genome-wide significance in 6911 cases and 11 814 controls (rs6104690, rs4510656, rs5003154 and rs4907479, P | 1 × 10(-6)), using additional data from existing GWAS datasets and targeted genotyping for studies that did not have GWAS data. In a combined analysis, which included data on up to 15 058 cases and 286 270 controls, two SNPs achieved genome-wide statistical significance: rs6104690 in a gene desert at 20p12.2 (P = 2.19 × 10(-11)) and rs4907479 within the MCF2L gene at 13q34 (P = 3.3 × 10(-10)). Imputation and fine-mapping analyses were performed in these two regions for a subset of 5551 bladder cancer cases and 10 242 controls. Analyses at the 13q34 region suggest a single signal marked by rs4907479. In contrast
TY - JOUR. T1 - Multivariate logistic regression for familial aggregation in age at disease onset. AU - Matthews, Abigail G.. AU - Finkelstein, Dianne M.. AU - Betensky, Rebecca. PY - 2007/6/1. Y1 - 2007/6/1. N2 - Familial aggregation studies seek to identify diseases that cluster in families. These studies are often carried out as a first step in the search for hereditary factors affecting the risk of disease. It is necessary to account for age at disease onset to avoid potential misclassification of family members who are disease-free at the time of study participation or who die before developing disease. This is especially true for late-onset diseases, such as prostate cancer or Alzheimers disease. We propose a discrete time model that accounts for the age at disease onset and allows the familial association to vary with age and to be modified by covariates, such as pedigree relationship. The parameters of the model have interpretations as conditional log-odds and log-odds ratios, which can ...
TY - CHAP. T1 - Complex Genetics of Alcoholism. AU - Edenberg, Howard. AU - Foroud, Tatiana. PY - 2014/2. Y1 - 2014/2. N2 - Genetic factors play a significant role in the risk for alcoholism, although environmental influences are also important. Alcohol use disorders are defined by symptomology and are heterogeneous, making the identification of specific genes that affect risk difficult. Several strategies have been applied to identify genes that contribute to alcoholism and alcohol-related phenotypes, including candidate gene studies, family-based linkage studies, and genome-wide association studies. Variants in the alcohol metabolizing genes ALDH2 and ADH1B confer some protection against alcohol dependence. Common variants in other genes, including ADH4, ADH1C, GABRA2, GABRG1, CHRNA5, CHRNA3, CHRM2, PECR, AUTS2, PDYN, OPRK1, and KCNJ6, have been associated with alcohol dependence or other alcohol-related phenotypes. Many of these results await further replication. Meta-analysis of large ...
Previous studies have suggested that polymorphisms in CASP8 on chromosome 2 are associated with breast cancer risk. To clarify the role of CASP8 in breast cancer susceptibility, we carried out dense genotyping of this region in the Breast Cancer Association Consortium (BCAC). Single-nucleotide polymorphisms (SNPs) spanning a 1 Mb region around CASP8 were genotyped in 46 450 breast cancer cases and 42 600 controls of European origin from 41 studies participating in the BCAC as part of a custom genotyping array experiment (iCOGS). Missing genotypes and SNPs were imputed and, after quality exclusions, 501 typed and 1232 imputed SNPs were included in logistic regression models adjusting for study and ancestry principal components. The SNPs retained in the final model were investigated further in data from nine genome-wide association studies (GWAS) comprising in total 10 052 case and 12 575 control subjects. The most significant association signal observed in European subjects was for the imputed intronic
In recent years the pace of discovery of genetic associations with type I diabetes (T1D) has accelerated, with the total number of confirmed loci, including the major histocompatibility complex (MHC) region, reaching 43. However, much of the deciphering of the associations at these, and the established T1D loci, has yet to be performed in sufficient numbers of samples or with sufficient markers. Here, 257 single-nucleotide polymorphisms (SNPs) have been genotyped in 19 candidate genes (INS, PTPN22, IL2RA, CTLA4, IFIH1, SUMO4, VDR, PAX4, OAS1, IRS1, IL4, IL4R, IL13, IL12B, CEACAM21, CAPSL, Q7Z4c4(5Q), FOXP3, EFHB) in 2300 affected sib-pair families and tested for association with T1D as part of the Type I Diabetes Genetics Consortiums candidate gene study. The study had approximately 80% power at alpha=0.002 and a minor allele frequency of 0.2 to detect an effect with a relative risk (RR) of 1.20, which drops to just 40% power for a RR of 1.15. At the INS gene, rs689 (-23 HphI) was the most associated
Recently, a locus on chromosome 6q22.33 (rs2180341) was reported to be associated with increased breast cancer risk in the Ashkenazi Jewish (AJ) population, and this association was also observed in populations of non-AJ European ancestry. In the present study, we performed a large replication analysis of rs2180341 using data from 31,428 invasive breast cancer cases and 34,700 controls collected from 25 studies in the Breast Cancer Association Consortium (BCAC). In addition, we evaluated whether rs2180341 modifies breast cancer risk in 3,361 BRCA1 and 2,020 BRCA2 carriers from 11 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Based on the BCAC data from women of European ancestry, we found evidence for a weak association with breast cancer risk for rs2180341 (per-allele odds ratio (OR) = 1.03, 95% CI 1.00-1.06, p = 0.023). There was evidence for heterogeneity in the ORs among studies (I(2) = 49.3%; p ...
We genotyped 2,861 cases of primary biliary cirrhosis (PBC) from the UK PBC Consortium and 8,514 UK population controls across 196,524 variants within 186 known autoimmune risk loci. We identified 3 loci newly associated with PBC (at P|5×10(-8)), increasing the number of known susceptibility loci …
The current challenge in biomedical research is to detect genetic risk factors involved in common complex diseases. The power to detect their role is generally poor in populations that have been large for a long time. It has been suggested that the power may be increased by taking advantage of the specificity of founder populations: linkage disequilibrium spanning larger regions and kinship coefficients being stronger than in large populations. A new method is proposed here, the Maximum Identity Length Contrast (MILC) which, in contrast with other existing methods, does not make the assumption of unique ancestry for the genetic risk factors. It is thus appropriate for a search for common genetic risk factors for complex diseases. Statistical properties of the method are discussed in realistic contexts.
Men with an inherited mutation linked to increased risk for prostate cancer may benefit from enhanced cancer screening. The National Cancer Institute opened a clinical trial for prostate cancer screening study looking at MRI to improve prostate cancer detection.
Objective Systemic lupus erythematosus (SLE; OMIM 152700) is a chronic autoimmune disease for which the aetiology includes genetic and environmental factors. ITGAM, integrin αΜ (complement component 3 receptor 3 subunit) encoding a ligand for intracellular adhesion molecule (ICAM) proteins, is an established SLE susceptibility locus. This study aimed to evaluate the independent and joint effects of genetic variations in the genes that encode ITGAM and ICAM. Methods The authors examined several markers in the ICAM1-ICAM4-ICAM5 locus on chromosome 19p13 and the single ITGAM polymorphism (rs1143679) using a large-scale case-control study of 17 481 unrelated participants from four ancestry populations. The single marker association and gene-gene interaction were analysed for each ancestry, and a meta-analysis across the four ancestries was performed. Results The A-allele of ICAM1-ICAM4-ICAM5 rs3093030, associated with elevated plasma levels of soluble ICAM1, and the A-allele of ITGAM rs1143679 ...
Relief is when you and the right researcher find each other Finding the right clinical trial for Multiple sclerosis susceptibility can be challenging. However, with TrialsFinder (which uses the Reg4ALL database and privacy controls by Private Access), you can permit researchers to let you know opportunities to consider - all without revealing your identity. ...
Using the candidate gene approach (discussed earlier in this chapter), many genes have been associated with asthma or asthma-related traits such as allergy and high concentrations of immunoglobulin E (IgE) in serum (table 2). Not all of these suspected asthma susceptibility genes have been replicated in multiple independent studies. One group of (allergic) asthma susceptibility genes is involved in innate immunity responses, encompassing pattern-recognition receptors, immunoregulatory cytokines and molecules involved in antigen presentation. A second group of asthma susceptibility genes are key players in T-helper type 2 (Th2)-cell differentiation and Th2- cell effector function. Th2 cells are T-lymphocytes that drive the production of allergic immunoglobulins (IgE) and the chronic airway inflammation in (allergic) asthma.. Linkage studies in families have discovered several novel asthma susceptibility genes that are expressed in epithelial cells and/or smooth muscle cells in the airways (table ...
Chromosome 5p15.33 has been identified as a lung cancer susceptibility locus, however the underlying causal mechanisms were not fully elucidated. Previous fine-mapping studies of this locus have relied on imputation or investigated a small number of known, common variants. This study represents a significant advance over previous research by investigating a large number of novel, rare variants, as well as their underlying mechanisms through telomere length. Variants for this fine-mapping study were identified through a targeted deep sequencing (average depth of coverage greater than 4000x) of 576 individuals. Subsequently, 4652 SNPs, including 1108 novel SNPs, were genotyped in 5164 cases and 5716 controls of European ancestry. After adjusting for known risk loci, rs2736100 and rs401681, we identified a new, independent lung cancer susceptibility variant in LPCAT1: rs139852726 (OR = 0.46, P = 4.73x10(-9)), and three new adenocarcinoma risk variants in TERT: rs61748181 (OR = 0.53, P = ...
Chromosome 5p15.33 has been identified as a lung cancer susceptibility locus, however the underlying causal mechanisms were not fully elucidated. Previous fine-mapping studies of this locus have relied on imputation or investigated a small number of known, common variants. This study represents a significant advance over previous research by investigating a large number of novel, rare variants, as well as their underlying mechanisms through telomere length. Variants for this fine-mapping study were identified through a targeted deep sequencing (average depth of coverage greater than 4000×) of 576 individuals. Subsequently, 4652 SNPs, including 1108 novel SNPs, were genotyped in 5164 cases and 5716 controls of European ancestry. After adjusting for known risk loci, rs2736100 and rs401681, we identified a new, independent lung cancer susceptibility variant in LPCAT1: rs139852726 (OR = 0.46, P = 4.73×10(-9)), and three new adenocarcinoma risk variants in TERT: rs61748181 (OR = 0.53, P = 2.64×10(-6)),
The first edition of Human Genome Epidemiology, published in 2004, discussed how the epidemiologic approach provides an important scientific foundation for studying the continuum from gene discovery to the development, applications and evaluation of human genome information in improving health and preventing disease. Since that time, advances in human genomics have continued to occur at a breathtaking pace.
The first edition of Human Genome Epidemiology, published in 2004, discussed how the epidemiologic approach provides an important scientific foundation for studying the continuum from gene discovery to the development, applications and evaluation of human genome information in improving health and preventing disease. Since that time, advances in human genomics have continued to occur at a breathtaking pace.
NIH Funding Opportunities and Notices in the NIH Guide for Grants and Contracts: Ancillary Studies to the NIDDK Inflammatory Bowel Disease Genetics Consortium (R01- Clinical Trial Optional) RFA-DK-17-017. NIDDK
OLIVEIRA, Martha Maria de et al. Single Nucleotide Polymorphisms (SNPs) of the TNF-a (-238/-308) gene among TB and nom TB patients: susceptibility markers of TB occurrence?. J. bras. pneumol. [online]. 2004, vol.30, n.4, pp.371-377. ISSN 1806-3713. https://doi.org/10.1590/S1806-37132004000400012.. BACKGROUND: Host genetic factors may play a role in the susceptibility to active tuberculosis (TB), and several polymorphisms in different cytokine coding genes have been described and associated with diseases to date. OBJECTIVES: To investigate whether polymorphisms within the promoter region of the TNF-a (-238/-308) coding genes are associated to the occurrence of active TB. METHODS: SNPs within the TNF-a gene were analyzed by PCR-RFLP among two groups of individuals: patients with TB (n = 234, and patients non TB (n = 113). RESULTS: In this study, the presence of the -238A allele was associated with susceptibility to TB disease occurrence and severity (p = 0,00002; OR = 0,15; IC = 0,06-0,36. On the ...
Epithelial ovarian cancer (EOC) has a heritable component that remains to be fully characterized. Most identified common susceptibility variants lie in non-protein-coding sequences. We hypothesized that variants in the 3 untranslated region at putative microRNA (miRNA)-binding sites represent funct …
This course focuses on the fundamental research methods and applications in the dynamic field of genetic epidemiology. To help students obtain a basic understanding of the field, the course includes topics such as assessing genetic influences on disease; advances in genomics technology; family based study designs for linkage, exome sequencing and case-parent trios; candidate gene and genome-wide association studies of both common and rare genetic variants; gene-environment interactions, epistasis and non-Mendelian genetics; software and web-based data resources; ethical issues in genetic epidemiology; and applications of genetic epidemiology to clinical practice and public health. Students will be exposed to a range of research approaches in genetic epidemiology, to examples of these approaches from the literature and from ongoing studies, and will have an opportunity to apply these methods by writing a grant application or human genome epidemiology review in their area of research ...
Finally, a risk score consisting of 47 T2D susceptibility gene variants showed a strong association with fasting glucose, T2D and HOMA-B. Interaction analysis suggested that its effect on fasting glucose levels might be modulated by BMI. The score was associated with greater increase in fasting glucose in obese individuals compared to overweight or normal individuals. The same effect was not observed for T2D risk, possibly because of reduced statistical power. When the variants were partitioned by their proposed physiologic mechanism in the disease, a strong association was found with decreased HOMA-B for one set of SNPs and with increased HOMA-IR for another. The genetic risk score associated with IR, but not the other genetic risk scores, showed a strong association with chronic kidney disease (CKD). Mendelian randomization analysis suggested a causal effect of IR on impaired glomerular filtration rate. The association was statistically significant after the exclusion of diabetic individuals ...
Psoriasis is really a physically, emotionally, and socially invalidating multifactorial disorder, with a substantial effect on the individuals standard of living. the most essential improvements in psoriasis biomarker finding, directing out those biomarkers that have also been analyzed in additional stress-related conditions, therefore emphasizing the partnership between psoriasis and tension. 1. Intro Psoriasis is really a chronic, immune-mediated, polygenic skin condition with a common occurrence affecting around 2% from the Caucasian human buy 139110-80-8 population [1, 2]. It really is a physically, psychologically, and socially invalidating condition with an excellent effect on the individuals standard of living [3]. Individuals with psoriasis frequently experience sociable stigma. Psoriasis can show up at any age group, but two peaks in age group starting point have already been reported: the very first between 20 and 30 years and the next between 50 and 60 years [4]. Men and women are ...
Previously, TP53 codon 72 polymorphisms have been implicated as risk factors for various cancers. A number of studies have conducted on the association of TP53 codon 72 polymorphisms with susceptibility to breast carcinoma and have yielded inconclusive results. The aim of the present study was to derive a more precise estimation of the relationship. We conducted a search in the Medline, EMBASE, OVID, Sciencedirect, and Chinese National Knowledge Infrastructure (CNKI) without a language limitation, covering all papers published up to Jan 2009. The associated literature was acquired through deliberate searching and selected based on the established inclusion criteria for publications. A total of seventeen case-control studies, including 12226 cases and 10782 controls, met the included criteria and thus were selected. Ultimately, the relevant data were extracted and further analyzed using systematic meta-analyses. Overall, no associations of TP53 codon 72 polymorphisms with breast carcinoma were observed
To explore the readiness of living, untested first-degree relatives (FDRs) to have cascade genetic testing (CGT) for a hereditary predisposition to cancer. Adults with a hereditary predisposition to cancer completed an anonymous, online survey about their genetic testing and their FDRs vital status, awareness of the variant, uptake of CGT, and readiness for CGT among living, untested FDRs using transtheoretical model stages of change. One hundred fifty participants completed the survey and reported 825 FDRs. Overall, 70.3% of FDRs were reportedly aware of the variant and 30.5% had completed CGT. Siblings had higher rates of awareness and CGT than parents or children (p | 0.001). Relatives sex was associated with awareness and CGT; mothers were aware and had CGT at higher rates than fathers (p = 0.049 and p | 0.001), sisters were aware and had CGT at higher rates than brothers (p = 0.041 and p = 0.002), and daughters had higher rates of awareness than sons (p = 0.038). Of 340 living, untested FDRs, 79
Alzheimers Disease Susceptibility Genes APOE and TOMM40, and Hippocampal Volumes in the Lothian Birth Cohort 1936. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
Academy of Finland Centre of Excellence in Complex Disease Genetics (CoECDG), Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki.
The purpose of the Alzheimers Disease Genetics Study is to help identify the genes that may be responsible for causing Alzheimers Disease (AD) by collecting genetic material from families with multiple members diagnosed with AD. Qualifying families will have two living blood-related individuals who have been diagnosed with or are showing symptoms of AD or dementia. Local study sites are located all over the United States, and arrangements may be made for eligible families who do not live near a participating site. The biological samples and data from these families will be made available to qualified researchers, who must sign a Materials Transfer Agreement (MTA) in order to protect the privacy rights of study participants before receiving DNA and data ...
BACKGROUND: Several genes encoding for DNA repair molecules implicated in maintaining genomic integrity have been proposed as cancer-susceptibility genes. Although efforts have been made to create synopses for specific fields that summarize the data from genetic association studies, such an overview is not available for genes involved in DNA repair. METHODS: We have created a regularly updated database of studies addressing associations between DNA repair gene variants (excluding highly penetrant mutations) and different types of cancer. Using 1087 datasets and publicly available data from genome-wide association platforms, meta-analyses using dominant and recessive models were performed on 241 associations between individual variants and specific cancer types that had been tested in two or more independent studies. The epidemiological strength of each association was graded with Venice criteria that assess amount of evidence, replication, and protection from bias. All statistical tests were ...
Part of the substantial unexplained familial aggregation of breast cancer may be due to interactions between common variants, but few studies have had adequate statistical power to detect interactions of realistic magnitude. We aimed to assess all two-way interactions in breast cancer susceptibility between 70 917 single nucleotide polymorphisms (SNPs) selected primarily based on prior evidence of a marginal effect. Thirty-eight international studies contributed data for 46 450 breast cancer cases and 42 461 controls of European origin as part of a multi-consortium project (COGS). First, SNPs were preselected based on evidence (P , 0.01) of a per-allele main effect, and all two-way combinations of those were evaluated by a per-allele (1 d.f.) test for interaction using logistic regression. Second, all 2.5 billion possible two-SNP combinations were evaluated using Boolean operation-based screening and testing, and SNP pairs with the strongest evidence of interaction (P , 10(-4)) were selected for ...
Three common mutations in the CARD15 (NOD2) gene are known to be associated with susceptibility to Crohn disease (CD), and genetic data suggest a gene dosage model with an increased risk of 2-4-fold in heterozygotes and 20-40-fold in homozygotes. However, the discovery of numerous rare variants of CARD15 indicates that some heterozygotes for the common mutations have a rare mutation on the other CARD15 allele, which would support a recessive model for CD. We addressed this issue by screening CARD15 for mutations in 100 CD patients who were heterozygous for one of the three common mutations. We also developed a strategy for evaluating potential disease susceptibility alleles (DSAs) that involves assessing the degree of evolutionary conservation of involved residues, predicted effects on protein structure and function, and genotyping in a large sample of cases and controls. The evolutionary analysis was aided by sequencing the entire coding region of CARD15 in three primates (chimp, gibbon, and ...
Pulmonary emphysema is defined as a nonuniform pattern of abnormal, permanent distention of the air spaces with destruction of the alveolar walls and eventually a reduced pulmonary capillary bed. It appears to be the end stage of a process that has progressed slowly for many years. Smoking is the major cause. In a few patients, there is familial predisposition associated with a plasma protein abnormality ( deficiency in alpha-1 antitrypsin), making the person sensitive to environmental factors ( air pollution, infectious agents, allergens). Emphysema manifests commonly in the fifth decade of life and is classified as follows:. ...
Other research groups also have found the G2385R mutation is at a higher frequency in Asian patients with Parkinsons disease, than in matched control subjects. These types of case and control genetic studies provide a powerful tool for researchers to find disease genes and risk factors in homogeneous or isolated populations where there has been little immigration. Interestingly, the present papers authors found evidence to suggest G2385R carriers share a common ancestor. They performed a genetic analysis looking at the inheritance pattern of a specific DNA sequence along chromosome 12 that includes the LRRK2 gene. Examining known genetic markers, which are short stretches of repeated DNA subject to variation in the number of times they repeat, their analysis showed a unique pattern of these DNA sequence markers is almost always passed from generation to generation along with the G2385R variant. Researchers used genetic theory to estimate the level of variation at these genetic markers between ...
Rare variants as low-penetrance alleles Rare variants will not be detectable by population association studies based on the use of linked polymorphic markers, even with very large case/control cohort studies. This is because of low allelic frequency and individually small contributions to the overall inherited susceptibility of a disease. These variants are less common…