New methods for studying complex diseases via genetic association studies. . 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.
The rapid growth of human genetics creates countless opportunities for studies of disease association. Given the number of potentially identifiable genetic markers and the multitude of clinical outcomes to which these may be linked, the testing and validation of statistical hypotheses in genetic epidemiology is a task of unprecedented scale. Meta-analysis provides a quantitative approach for combining the results of various studies on the same topic, and for estimating and explaining their diversity. Here, we have evaluated by meta-analysis 370 studies addressing 36 genetic associations for various outcomes of disease. We show that significant between-study heterogeneity (diversity) is frequent, and that the results of the first study correlate only modestly with subsequent research on the same association. The first study often suggests a stronger genetic effect than is found by subsequent studies. Both bias and genuine population diversity might explain why early association studies
The rapid growth of human genetics creates countless opportunities for studies of disease association. Given the number of potentially identifiable genetic markers and the multitude of clinical outcomes to which these may be linked, the testing and validation of statistical hypotheses in genetic epi …
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Established guidelines for causal inference in epidemiological studies may be inappropriate for genetic associations. A consensus process was used to develop guidance criteria for assessing cumulative epidemiologic evidence in genetic associations. A proposed semi-quantitative index assigns three levels for the amount of evidence, extent of replication, and protection from
... , a database that aims to provide an unbiased, centralized, publicly available and regularly updated collection of genetic association studies performed on MS phenotypes.
최근에 병원의 의료 현장에서 NGS 타겟 시퀀싱 패널을 이용하면서 다양한 유전자들을 동시에 검사하는 건수가 폭발적으로 증가하고 있습니다. 다만 안타깝게도 많은 경우에 실제로 그 유전체 정보와 데이터를 충분히 활용하지 못하고 있음을 많이 느낍니다. 즉, 돈을 들여서 구축된 파이프 라인을 통해서 유전체 데이터 생산은 되는데, 이후에 변이들에 대한 적절한 해석을 하고, 환자에 적용하는데 까지는 아직 더 경험이 필요한 것…
The publication of Khush et al. in this months issue (1) provides an opportunity to consider some of the challenges in doing genetic association studies in transplantation. While rigid rules for such manuscript submissions are neither warranted nor desirable, there are several guidelines published for gene association study publications that are well worth reviewing (2,3). These guidelines are also directly relevant to gene association studies in transplantation and the Journal does not need to create any new guidelines for this reason. Thus, in the present editorial, I will use this new article in the Journal to consider some science-based guidelines specifically for transplantation.. There is no question that the physiological stability of the donor prior to surgical organ recovery is a significant factor in effectively managing the donor procedure, influences the selection for cardiac donation and impacts the early posttransplant course of the recipients. With that context, Khush et al. ...
The development of congenital heart defects (CHDs) involves a complex interplay between genetic variants, epigenetic variants, and environmental exposures. Previous studies have suggested that susceptibility to CHDs is associated with maternal genotypes, fetal genotypes, and maternal-fetal genotype (MFG) interactions. We conducted a haplotype-based genetic association study of obstructive heart defects (OHDs), aiming to detect the genetic effects of 877 SNPs involved in the homocysteine, folate, and transsulfuration pathways. Genotypes were available for 285 mother-offspring pairs with OHD-affected pregnancies and 868 mother-offspring pairs with unaffected pregnancies. A penalized logistic regression model was applied with an adaptive least absolute shrinkage and selection operator (lasso), which dissects the maternal effect, fetal effect, and MFG interaction effects associated with OHDs. By examining the association between 140 haplotype blocks, we identified 9 blocks that are potentially ...
Genetic Association Study of Adiposity and Melanocortin-4 Receptor MC4R Common Variants: Replication and Functional Characterization of Non-Coding Regions. . 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.
Supplementary Material for: Integrating Multiple Correlated Phenotypes for Genetic Association Analysis by Maximizing Heritability
Association studies examine well-characterized sites of the genome - the genetic markers - to identify potential associations between the former and a phenotype (disease status, blood pressure, response to medicine in the biomedical domain ... ; wheat flour plasticity, muscular mass in the agronomic domain ...). Societal and economic impacts are expected from advances in this active research field, at the cross of genetics and bioinformatics: scientific progress in medicine (evidence of individual genetic susceptibility to drugs, personalized medicine), societal evolution (early gene susceptibility detection for better prevention or surveillance, population aging), control of public health expenditure, nutrition improvement for entire populations ...
Sigma-Aldrich offers abstracts and full-text articles by [ChangJiang Xu, Martin Ladouceur, Zari Dastani, J Brent Richards, Antonio Ciampi, Celia M T Greenwood].
The American Genetic Association (AGA), formerly the American Breeders Association, is a USA-based learned society dedicated to the study of genetics. Founded in 1903, the organization publishes the Journal of Heredity. The American Genetic Association (AGA), formerly the American Breeders Association, is a professional organization founded to encourage the study of comparative genetics and genomics, and to promote the application of genetic and genomic methods to the documentation, conservation, and management of organismal diversity. The American Breeders Association held its first meeting in 1903 to discuss the "new" science of genetics that arose from Charles Darwins theory of evolution and Gregor Mendels discoveries of the laws of inheritance. The organization was established "to study the laws of breeding and to promote the improvement of plants and animals by the development of expert methods of breeding." [1] In 1914, the American Breeders Association broadened its scope and became ...
Genetic association study results serve three main purposes: (1) to identify risk markers that can be used to predict high-risk individuals who may benefit from
© Springer International Publishing Switzerland 2014. The quest to discover genetic variants that affect the human brain will be accelerated by screening brain images from large populations. Even so, the wealth of information in medical images is often reduced to a single numeric summary, such as a regional volume or an average signal, which is then analyzed in a genome wide association study (GWAS). The high cost and penalty formultiple comparisons often constrains us from searching over the entire image space. Here, we developed a method to compute and boost power to detect genetic associations in brain images. We computed voxel-wise heritability estimates for fractional anisotropy in over 1,100 DTI scans, and used the results to threshold FA images from new studies. We describe voxel selection criteria to optimally boost power, as a function of the sample size and allele frequency cut-off. We illustrate our methods by analyzing publicly-available data from the ADNI2 project.
EPI293 Design and analysis of gene association studies Winter Term 2008 Lecture 2: Patterns of LD and tag SNP selection Peter Kraft [email protected] – A free PowerPoint PPT presentation (displayed as a Flash slide show) on PowerShow.com - id: 65d8d6-ODkxZ
To find the MLE, the likelihood function is first obtained, which is given by n L(θ ,x1 , . . , xn ) = f (xi ,θ ), i=1 where f (x,θ ) is the PDF or the distribution function. We often use L(θ ) for the likelihood function. An estimate of θ , denoted by θ , is the MLE for θ if it maximizes the likelihood function. , Θ = (0, 1) for the binomial probability p. Then the MLE θ satisfies L(θ ) = max L(θ ). 6) We may also write θ = arg max L(θ ) = arg max l(θ ), θ∈Θ θ∈Θ where l(θ ) = log L(θ ) is the log-likelihood function. 0 ≤ x ≤ n. Let Xi be the number of ith outcomes of a multinomial random variable. The mean and variance of Xi are given by E(Xi ) = npi and Var(Xi ) = pi (1 − pi )/n. The covariance of two outcomes Xi and Xj is given by Cov(Xi , Xj ) = −pi pj /n for i = j . Thus, Corr(Xi , Xj ) = − pi pj . (1 − pi )(1 − pj ) The Normal Distribution The normal distribution is the most commonly used distribution in statistics. Let X be a random variable that ...
Stephen Turner, Loren L. Armstrong, Yuki Bradford, Christopher S. Carlson, Dana C. Crawford, Andrew T. Crenshaw, Mariza de Andrade, Kimberly F. Doheny, Jonathan L. Haines, Geoffrey Hayes, Gail Jarvik, Lan Jiang, Iftikhar J. Kullo, Rongling Li, Hua Ling, Teri A. Manolio, Martha Matsumoto, Catherine A. McCarty, Andrew N. McDavid, Daniel B. Mirel, Justin E. Paschall, Elizabeth W. Pugh, Luke V. Rasmussen, Russell A. Wilke, Rebecca L. Zuvich, Marylyn D. ...
We investigated several gene-based grouping strategies for rare variants and analyzed both the real and simulated phenotype data. We observed that further restriction of rare variants based on annotation is promising (e.g., from coding to protein damaging); however, we did not observe statistically significant results after adjusting for multiple hypothesis testing. The strategies presented so far focused on coding variants. We also considered two other strategies that include non-coding variants but restricted to variants that belong to conservation tier 1 group (T1) (PhastCons score ,0 and PhyloP score ,1) and tier 2 group (T2) (PhastCons ,400 and PhyloP score ,1.5) (see Nalpathamkalam et al [13] for more details on these annotation strategies). These lead to grouping variants from the same gene, which are (d) protein-changing or conservative T1 variants with 11,227 high-quality variants and (e) protein-damaging or conservative T2 variants with 4196 high-quality variants (Table 2). These ...
Genotype-phenotype correlations exist for homozygous or compound heterozygous mutations in ABCA3. Frameshift or nonsense ABCA3 mutations are predictive of neonatal presentation and poor outcome, whereas missense, splice site, and insertion/deletions are less reliably associated with age of presentat …
Welcome to the LongevityMap, a database of human genetic variants associated with longevity. Negative results are also included in the LongevityMap to provide visitors with as much information as possible regarding each gene and variant previously studied in context of longevity. As such, the LongevityMap serves as a repository of genetic association studies of longevity and reflects our current knowledge of the genetics of human longevity.. ...
Arking, D. E., S. L. Pulit, L. Crotti, P. van der Harst, P. B. Munroe, T. T. Koopmann, N. Sotoodehnia, et al. 2014. "Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization." Nature genetics 46 (8): 826-836. doi:10.1038/ng.3014. http://dx.doi.org/10.1038/ng.3014 ...
The Journal of Pathology is now soliciting submissions of primary research based on massively parallel sequencing taking advantage of novel insights into the genetic basis of human diseases, including the identification of new genotype-phenotype associations and novel driver mutations, characterization of patterns of genetic instability, and on the topic of intra-tumour genetic heterogeneity ...
Suicidal behaviours, which range from suicidal ideation to suicide attempts and completed suicide, represent a fatal dimension of mental ill-health. The involvement of genetic risk factors in suicidal behaviour is supported by family, twin, and adoption studies. The aim of this paper is to review recent genetic association studies in suicidal behaviours including (i) case-control studies, (ii) family-based association studies and (iii) genome-wide association studies (GWAS). Various studies on genetic associations have tended to suggest that a number of genes (e.g., tryptophan hydroxylase, serotonin receptors and transporters or brain-derived neurotrophic factors) are linked to suicidal behaviours, but these findings are not consistently supported by the results obtained. Although the candidate-gene approach is useful, it is hampered by the present state of knowledge concerning the pathophysiology of diseases. Interpretations of GWAS results are mostly hindered by a lack of annotation describing the
TY - JOUR. T1 - Candidate gene association studies of genes involved in neuronal cholinergic transmission in Alzheimers disease suggests choline acetyltransferase as a candidate deserving further study. AU - Cook, Lynnette J.. AU - Ho, Luk W.. AU - Wang, Lin. AU - Terrenoire, Edith. AU - Brayne, Carol. AU - Evans, John Grimley. AU - Xuereb, John. AU - Cairns, Nigel J.. AU - Turic, Dragana. AU - Hollingworth, Paul. AU - Moore, Pamela J.. AU - Jehu, Luke. AU - Archer, Nicola. AU - Walter, Sarah. AU - Foy, Catherine. AU - Edmondson, Amanda. AU - Powell, John. AU - Lovestone, Simon. AU - Williams, Julie. AU - Rubinsztein, David C.. PY - 2005/1/5. Y1 - 2005/1/5. N2 - Consistent deficits in the cholinergic system are evident in the brains of Alzheimers Disease (AD) patients, including reductions in the activities of acetylcholine, acetylcholinesterase (AChE), and choline acetyltransferase (ChAT), increased butyrylcholinesterase (BChE) activity, and a selective loss of nicotinic acetylcholine ...
Genetic association studies have identified and replicated susceptibility genes for asthma in 3 major types of studies: Candidate gene studies Positional cloning using linkage studies Genome-wide association studies (GWAS) Candidate gene studies Candidate gene studies represent the most common form of genetic association study performed to f...
TY - JOUR. T1 - Detecting significant genotype-phenotype association rules in bipolar disorder. T2 - market research meets complex genetics. AU - Breuer, René. AU - Mattheisen, Manuel. AU - Frank, Josef. AU - Krumm, Bertram. AU - Treutlein, Jens. AU - Kassem, Layla. AU - Strohmaier, Jana. AU - Herms, Stefan. AU - Mühleisen, Thomas W.. AU - Degenhardt, Franziska. AU - Cichon, Sven. AU - Nöthen, Markus M.. AU - Karypis, George. AU - Kelsoe, John. AU - Greenwood, Tiffany. AU - Nievergelt, Caroline. AU - Shilling, Paul. AU - Shekhtman, Tatyana. AU - Edenberg, Howard. AU - Craig, David. AU - Szelinger, Szabolcs. AU - Nurnberger, John. AU - Gershon, Elliot. AU - Alliey-Rodriguez, Ney. AU - Zandi, Peter P. AU - Goes, Fernando S. AU - Schork, Nicholas. AU - Smith, Erin. AU - Koller, Daniel. AU - Zhang, Peng. AU - Badner, Judith. AU - Berrettini, Wade. AU - Bloss, Cinnamon. AU - Byerley, William. AU - Coryell, William. AU - Foroud, Tatiana. AU - Guo, Yirin. AU - Hipolito, Maria. AU - Keating, ...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
This year we have also provided some guidance on the requirements for publication of genetic association studies in Thorax. We noticed that many studies submitted have been underpowered or poorly designed, and we have published an editorial containing guidance on some of the key issues that need to be addressed when assessing the validity of genetic association studies. Already the standard of genetics papers in the journal has improved, and we urge our authors to study these requirements.8,9. We have continued to develop our educational features, including Airwaves at the front of the journal, Lung Alerts (short summaries of papers published in general and non-respiratory journals and serviced by our younger readers),10 and "Images in Thorax".6 This series has proved very popular and educational and we have received 111 high quality submissions for the Images series over the year. The series has been available free of charge since November 2003 in a collection on the Thorax website ...
Using the classic study by Knowler et al., we will detail how population stratification can confound the relationship between a genetic marker and disease. We will discuss how population stratification can affect the results and interpretation of a genetic association study. Finally, we will list recent review papers that address this issue in more detail. This module assumes that the reader has read the article below.. Knowler WC, Williams RC, Pettitt DJ, Steinberg AG. Gm3;5,13,14 and type 2 diabetes mellitus: an association in American Indians with genetic admixture. Am J Hum Genet 1988;43(4):520-6. (PubMed Link)*If you are having trouble accessing this article, please contact us.. ...
AlzGene is a collection of published Alzheimers disease genetic association studies, with random-effects meta-analyses for polymorphisms with genotype data in at least three case-control samples.. Note to all users: the redesign of the AlzGene database code has been completed (please visit our sister database at ALSGene.org and PDGene.org). We are aiming to include GWAS meta-analysis results published in 2013 by the International Genomics of Alzheimers Project (IGAP) consortium. Once IGAP has agreed to share their data on AlzGene, this data will be posted on the new database interface. Please note that during this process, the legacy version of AlzGene is not being updated. We apologize for the inconvenience. Posted in Sept 2015. SEARCH THE ALZGENE DATABASE. ...
Background Power calculators are currently available for the design of genetic association studies of binary phenotypes and quantitative traits, but not for
Strategic research project of the University of Oulu Focus institute: Biocenter Oulu Faculty: Faculty of Science (FSCI) The genetics of quantitative variation and the factors influencing patterns of
...Mountain View Calif. January 28 2014 23andMe the leading personal g...Previous research has shown that both asthma and hay fever share 50-90... While previous analyses provided evidence of a stronger genetic assoc...By considering the phenotype of asthma-with-hay fever 11 independent ...,23andMe,helps,identify,11,new,genetic,associations,for,asthma-with-hay,fever,biological,biology news articles,biology news today,latest biology news,current biology news,biology newsletters
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Abstract: There is a region with a high risk for esophageal squamous cell carcinoma (ESCC) in the northeast of Iran. Previous studies suggest that hereditary factors play a role in the high incidence of cancer in the region. We selected 22 functional variants (and 130 related tagSNPs) from 15 genes that have been associated previously with the risk of ESCC. We genotyped a primary set of samples from 451 Turkmens (197 cases and 254 controls). Seven of 152 variants were associated with ESCC at the P = 0.05 level; these single nucleotide polymorphisms were then studied in a validation set of 549 cases and 1,119 controls, which included both Turkmens and non-Turkmens. The association observed for a functional variant in ADH1B was confirmed in the validation set, and that of a tagSNP in MGMT, the association was borderline significant in the validation set, after correcting for multiple testing. The other 5 variants that were associated in the primary set were not significantly associated in the ...
To our knowledge, this study is the first to use the CC population in a genome-wide association analysis of high-resolution trabecular bone traits. Our results replicate previous association analyses, confirm previous in vivo and in vitro experiments, and suggest new candidate genes for the regulation of trabecular bone microstructure. The roles of these latter genes will require validation in future studies both in vivo and in vitro. We thus provide a valuable resource for further research aimed at understanding the underlying genetic determinants of complex trabecular structure.. Our association analyses were enhanced by virtue of ancestral sequence information that enabled us to deduce QTNs that segregate differentially in the CC lines, thus reducing false positives and assisting in the identification of potential candidate genes. This imputations power depends on (a) the accuracy of the catalogues of variants in the CC founders (as determined from resequencing the strains by Keane et al. ...
In this work, we built a pipeline, extTADA, for the integrated Bayesian analysis of DN mutations and rare CC variants to infer rare-variant genetic architecture parameters and identify risk genes. We applied extTADA to data available for SCZ and four other NDDs (Additional file 1: Figure S1).. The extTADA pipeline extTADA is based on previous work in autism sequencing studies, TADA [16, 31]. It conducts a full Bayesian analysis of a simple rare-variant genetic architecture model and it borrows information across all annotation categories and DN and CC samples in genetic parameter inference, which is critical for sparse rare-variant sequence data. Using MCMC, extTADA samples from the joint posterior density of risk-gene proportion and mean relative risk parameters, and provides gene-level disease-association BFs, PPs, and FDRs. We hope that extTADA (https://github.com/hoangtn/extTADA) will be generally useful for rare-variant analyses across complex traits. extTADA can be used for rare CC variant ...
Recent successful discoveries of potentially causal single nucleotide polymorphisms (SNPs) for complex diseases hold great promise, and commercialization of genomics in personalized medicine has already begun. The hope is that genetic testing will benefit patients and their families, and encourage positive lifestyle changes and guide clinical decisions. However, for many complex diseases, it is arguable whether the era of genomics in personalized medicine is here yet. We focus on the clinical validity of genetic testing with an emphasis on two popular statistical methods for evaluating markers. The two methods, logistic regression and receiver operating characteristic (ROC) curve analysis, are applied to our age-related macular degeneration dataset. By using an additive model of the CFH, LOC387715, and C2 variants, the odds ratios are 2.9, 3.4, and 0.4, with p-values of 10−13, 10−13, and 10−3, respectively. The area under the ROC curve (AUC) is 0.79, but assuming prevalences of 15%, 5.5%, and 1.5%
Introduction. Genetic epidemiology is focused on the study of the genetic causes that determine health and diseases in populations. To achieve this goal a common strategy is to explore differences in genetic variability between diseased and nondiseased individuals. Usual markers of genetic variability are single nucleotide polymorphisms (SNPs) which are changes in just one base in the genome. The usual statistical approach in genetic epidemiology study is a marginal analysis, where each SNP is analyzed separately for association with the phenotype. Motivation. It has been observed, that for common diseases the single-SNP analysis is not very powerful for detecting genetic causing variants. In this work, we consider Gene Set Analysis (GSA) as an alternative to standard marginal association approaches. GSA aims to assess the overall association of a set of genetic variants with a phenotype and has the potential to detect subtle effects of variants in a gene or a pathway that might be missed when ...
Children from The Western Australian Pregnancy Cohort (Raine; n = 1,506) Study were genotyped at 17 genetic loci shown to be associated with childhood obesity (FTO, MC4R, TMEM18, GNPDA2, KCTD15, NEGR1, BDNF, ETV5, SEC16B, LYPLAL1, TFAP2B, MTCH2, BCDIN3D, NRXN3, SH2B1, MRSA) and an obesity-risk-allele-score was calculated as the total number of risk alleles possessed by each individual. To determine the statistical method that fits these data and has the ability to detect genetic differences in BMI growth profile, four methods were investigated: linear mixed effects model, linear mixed effects model with skew-t random errors, semi-parametric linear mixed models and a non-linear mixed effects model. Of the four methods, the semi-parametric linear mixed model method was the most efficient for modelling childhood growth to detect modest genetic effects in this cohort. Using this method, three of the 17 loci were significantly associated with BMI intercept or trajectory in females and four in ...
Genetic causes of disease, including stroke, range from classic mendelian (a single gene leads to disease) to complex (multiple genes contribute to risk for disease in combination with other genetic and/or environmental factors). One method of identifying genetic risk factors is the candidate gene association study, in which a given polymorphism in a gene of interest is compared between cases or controls; if the polymorphism is more common in affected subjects, a contribution to risk for disease is implied. A candidate gene is usually selected because the gene product is intuitively related to the disease process. Further studies in other populations will reveal whether findings from both association and candidate gene studies can be generalized. Because stroke includes multiple clinically relevant subgroups, the appropriate phenotyping approach is not yet known. It also is unclear whether the biological factors contributing to risk for one type of stroke are the same as those for the other ...
2953 Background: During the last few decades, tremendous effort has been put forth to identify the sources of genetic susceptibility to cancer. Continuing advances in genotyping technologies and the set up of observational studies with DNA sample collections have resulted in a large and increasing number of genetic association studies. This leads us to the question about the overall contribution of these studies to our current understanding of the genetic susceptibility to cancer. In an attempt to synthesize previous association studies and overcome small sample size issues of individual studies, meta- and pooled analyses have been used as a systematic approach of integrating results from a number of independent studies to identify a trend in the data. Methods: To evaluate the overall progress of observational studies on genetic variants and cancer risk, we systematically examined the published results of meta- and pooled analyses for genetic polymorphisms and risk of cancer. For this analysis, ...
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Deadline for application 14/10. We are welcoming candidates with a technical background on statistics or machine learning and with a high interest in the development of an engineering application.. ---------------------------------------------------------------------------------------------------------. An opportunity has arisen for a talented statistician with an interest in methodology development to join Dr Paul Newcombes group at the MRC Biostatistics Unit, Cambridge University. In a recent trend meta-GWAS, comprising tens of thousands of people, have boosted the power of genetic association studies. However, the availability of many correlated genetic variants as well as the logistics of sharing data on such a large scale presents analytical challenges and typically variants are only analysed one-at-a-time. This complicates interpretation and the ability of fine-mapping efforts to identify a small set of variants for functional follow-up. The proposed initial project will focus on ...
Some peoples brains may harbor their own built-in defense system agai...In the latest Neuropsychiatric Genetics section of the American Jou... These results are preliminary but do suggest that genetic differe... This kind of knowledge is important for the development of both pr...The new genetic association study compared DNA samples from 174 par...,Natures,own,antidote,to,cocaine,biological,biology news articles,biology news today,latest biology news,current biology news,biology newsletters
23andMe has participated in the first ever genome-wide association study of the combined asthma-with-hay fever phenotype. Led by researchers at the QIMR Berghofer Medical Research Institute, the study identified 11 independent ...
Haplotype: rs769087 - rs1006737 - rs2159100 - rs4765905 - rs2370413 - rs7297582 - rs758170 - rs1860002(G-G-G-C-A-G-G-A), rs769087 - rs1006737 - rs2159100 - rs4765905 - rs2370413 - rs7297582 - rs758170 - rs1860002(A-A-A-G-G-A-A-G), rs769087 - rs1006737 - rs2159100 - rs4765905 - rs2370413 - rs7297582 - rs758170 - rs1860002(G-G-G-C-G-G-G-G), rs769087 - rs1006737 - rs2159100 - rs4765905 - rs2370413 - rs7297582 - rs758170 - rs1860002(G-G-G-C-G-G-G-A), rs769087 - rs1006737 - rs2159100 - rs4765905 - rs2370413 - rs7297582 - rs758170 - rs1860002(G-G-G-C-G-A-G-G), rs769087 - rs1006737 - rs2159100 - rs4765905 - rs2370413 - rs7297582 - rs758170 - rs1860002(A-A-A-G-G-G-A-G), rs769087 - rs1006737 - rs2159100 - rs4765905 - rs2370413 - rs7297582 - rs758170 - rs1860002(G-G-G-C-A-G-G-G), rs769087 - rs1006737 - rs2159100 - rs4765905 - rs2370413 - rs7297582 - rs758170 - rs1860002(G-G-G-C-G-A-G-A), rs769087 - rs1006737 - rs2159100 - rs4765905 - rs2370413 - rs7297582 - rs758170 - rs1860002(A-A-A-G-G-G-G-G), rs769087 ...
RS6B_SCHPO (Q9C0Z7 ), RS6B_YEAST (P0CX38 ), RS6E_AERPE (Q9Y9B6 ), RS6E_ARCFU (O29739 ), RS6E_CALMQ (A8MA52 ), RS6E_HALLT (B9LR51 ), RS6E_HALMA (P21509 ), RS6E_HALS3 (B0R815 ), RS6E_HALSA (Q9HMJ5 ), RS6E_HALWD (Q18DP5 ), RS6E_HYPBU (A2BJZ7 ), RS6E_METAC (Q8TQL4 ), RS6E_METAR (Q0W8B4 ), RS6E_METBF (Q466D6 ), RS6E_METBU (Q12Z92 ), RS6E_METJA (P54067 ), RS6E_METKA (Q8TVE6 ), RS6E_METMA (Q8PU79 ), RS6E_METS5 (A4YIY0 ), RS6E_METST (Q2NGM7 ), RS6E_METTH (O26360 ), RS6E_NANEQ (Q74MJ5 ), RS6E_NATPD (Q3ISW0 ), RS6E_NITMS (A9A110 ), RS6E_PYRAB (Q9UYS3 ), RS6E_PYRAE (Q8ZX25 ), RS6E_PYRAR (A4WIK0 ), RS6E_PYRCJ (A3MUD0 ), RS6E_PYRFU (Q8U3H8 ), RS6E_PYRHO (O58349 ), RS6E_PYRIL (A1RUW1 ), RS6E_PYRNV (B1YCP4 ), RS6E_STAMF (A3DMS1 ), RS6E_SULIA (C3MZ52 ), RS6E_SULIK (C4KID0 ), RS6E_SULIL (C3MR04 ), RS6E_SULIM (C3MWZ2 ), RS6E_SULIY (C3N772 ), RS6E_SULSO (Q980A6 ), RS6E_SULTO (Q975N7 ), RS6E_THEKO (Q5JDK8 ), RS6E_THEON (B6YW70 ), RS6E_THESM (C6A2D7 ), RS6_AEDAE (Q9U761 ), RS6_AEDAL (Q9U762 ), RS6_APLCA (Q9BMX5 ), ...
Author Summary One focus of human genetics is localizing genes that are involved in the etiology of complex diseases. Although emphasis has been placed on mapping common variants, recent studies have demonstrated that rare variants also play an important role in complex trait etiology and their identification should have a greater impact on risk assessment, disease prevention, and treatment due to their large genetic effects. Genome-wide association studies are used to identify common variants by genotyping tagSNPs that are proxies for common causal variants. This study design is not adequately powered for association studies of rare variants; instead, causal variants must be identified and then analyzed. With the development of sequencing technologies, it is feasible to sequence candidate genes and, soon, entire genomes to obtain data on rare variants for complex disease association studies. We investigated several questions that are germane to the discovery of rare variants within a sample; for
Sigma-Aldrich offers abstracts and full-text articles by [Xingwang Li, Jing Zhang, Yang Wang, Jue Ji, Fengping Yang, Chunling Wan, Peng Wang, Guoyin Feng, Klaus Lindpaintner, Lin He, Guang He].
Background: Multiple genome-wide and candidate gene association studies have been performed in search of common risk variants for breast cancer. Recent large meta analyses, consolidating evidence from these studies, have been consistent in highlighting the caspase-8 (CASP8) gene as important in this regard. In order to define a risk haplotype and map the CASP8 gene region with respect to underlying susceptibility variant/s, we screened four genes in the CASP8 region on 2q33-q34 for breast cancer risk. Methods: Two independent data sets from the United Kingdom and the United States, including 3,888 breast cancer cases and controls, were genotyped for 45 tagging single nucleotide polymorphisms (tSNP) in the expanded CASP8 region. SNP and haplotype association tests were carried out using Monte Carlo based methods. Results: We identified a three-SNP haplotype across rs3834129, rs6723097 and rs3817578 that was significantly associated with breast cancer (p,5×10-6), with a dominant risk ratio and ...
In Phenome-Wide Association Studies (PheWAS), the association between single nucleotide polymorphisms (SNPs) and an extensive range of phenotypic measurements are calculated in a high throughput, unbiased manner. The phenotypic data used in PheWAS can come from a variety of sources. One possible source is epidemiologic health surveys linked to genotypic data that include measurements of intermediate traits or biomarkers such as blood cell counts and blood pressure measurements, as well as information on case/control status for multiple clinical conditions and risk factors such as presence/absence of diabetes or hypertension. One such example is the Population Architecture Using Genomics (PAGE) network, which is a National Human Genome Research Institute (NHGRI)-supported network of four study sites and a coordinating center accessing eight extensively characterized studies for PheWAS studies in diverse populations [1, 2]. These survey-based PheWAS efforts are complimentary to on-going PheWAS ...
The National Heart, Lung, and Blood Institute (NHLBI)s Next Generation Genetic Association Studies Program (Next Gen) was created to bank stem cell lines sourced from patients in genome-wide association studies (GWAS). The goal of the Next Gen Lipid Conditions sub-section - a collaborative effort between Stephen A. Duncan, Ph.D., chair of regenerative medicine at MUSC and Daniel J. Rader, M.D. and Edward E. Morrisey, Ph.D., both at the University of Pennsylvania - is to help determine the genetic sources of heart, lung or blood conditions that also include the liver.. The GWAS studies map the genomes in hundreds of people as a way to look for genetic mutation patterns that differ from the genomes of healthy individuals. As GWAS study map more genomes, they become more likely to find the correct genetic mutations that cause a disease. Once a panel of suspected mutations is built, stem cells from these individuals can be manipulated in culture dishes to differentiate into any of the bodys cells. ...
Genome wide association studies (GWAS) have identified more than 50 loci associated with genetic risk of type 1 diabetes (T1D). Several T1D candidate genes have been suggested or identified within these regions, but the molecular mechanisms by which they contribute to insulitis and βeta-cell destruction remain to be clarified. More than 60% of the T1D candidate genes are expressed in human pancreatic islets, suggesting that they contribute to T1D by regulating at least in part pathogenic mechanisms at the βeta-cell level. Recent studies by our group indicate that important genetically regulated pathways in βeta-cells include innate immunity and antiviral activity, involving RIG-like receptors (particularly MDA5) and regulators of type I IFNs (i.e. PTPN2, USP18 and TYK2), and genes related to βeta-cell phenotype and susceptibility to pro-apoptotic stimuli (i.e. GLIS3). These observations reinforce the concept that the early pathogenesis of T1D is characterized by a dialog between the immune ...
PMID 23838578] Genetic variants rs2393903 at 10q21.2 and rs6010620 at 20q13.33 are associated with clinical features of atopic dermatitis in the Chinese Han population ...
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Correlations between HRPT2 mutations and the clinical manifes-tations of HPT-JT appear to be absent. An analysis of 5 unrelat-ed patients and their families
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Due to the remarkable concordance between the role that TG2 plays in increasing these immunogenic peptides affinity for DQ2, the identity of TG2 as the target of the autoantibody response, and the strong genetic association of DQ2 with disease, research into celiac pathogenesis has largely focused on the adaptive branch of the immune response ...
|%=strTitleKey%>--CNKI翻译助手:覆盖专业领域最全面的科技术语英汉/汉英辞典,文献、术语中英互译的好帮手,词汇句子段落应有尽有。--中国知网-中文学术资源门户
Plasmid pMSCVbsd-PPARD-L433F from Dr. Till Adhikarys lab contains the insert PPARD L433F and is published in BioRxiv This plasmid is available through Addgene.
On the left you see the clue as it is currently displayed. Enter your correction on the right by editing the text directly. The top left field is the clues value, either as given on the board, or, if a Daily Double, the value of the contestants wager. If the clue is a Daily Double, check the checkbox to the right of this field. The top right field is the clue order number representing the order of the clues selection amongst other clues in the round. The large blue field is for the clue text, which should be entered as closely as possible to how it appears on the show, with the exception that the words should not be all caps. Links to media clue files should be entered with HTML-style hyperlinks. Next come the nicknames of the three contestants in the form of response toggles: single clicks on the name change its color from white (no response) to green (correct response) to red (incorrect response) and back. Below this should be typed the correct response (only the most essential part--it ...
The 9p21 locus, a strong risk locus for coronary arterial disease, has been also associated with other cardiovascular disease including ischemic stroke (IS) in Caucasians. However, the association between 9p21 locus and IS in Chinese Han population is still debatable because of ambiguous results reported previously. Genetic heterogeneity between Southern and Northern Chinese Han populations could be one of the reasons for this uncertainty. Four genetic variants selected from the three conjunctional LD blocks within the 44 kb candidate region on chromosome 9p21 were genotyped in 1,429 IS patients and 1,191 healthy controls from the Northern Chinese Han population. Among the four studied variants, the G allele of the SNP rs2383207 was significantly associated with IS with allele frequency 66.8% in patients and 63.4% in controls. This association appears to be dominant with an OR of 1.417 (p=0.003) for people with either GG or AG genotypes. We did not find any association for the other three SNPs
In a prospective population-based multi-ethnic sample, we tested 29 599 SNPs densely mapping loci with potential roles in cardiovascular physiology for association with carotid IMT. Using a codominant linear regression model, corrected for ethnicity, age, sex, systolic blood pressure, BMI, smoking status, and presence of dyslipidemia therapy, no associations were discovered at a Bonferroni corrected significance. However, Bonferroni correction is likely overly conservative in the context of a dense gene-centric chip covering loci that have a higher prior probability of association. The most strongly associated SNP was rs3791398 (P=1.8e-5) and is found within histone deacetylase 4 (HDAC4). Examining 15 loci that have been significantly associated with IMT in candidate gene investigations, 7 contained a SNP that was associated with IMT (P≤0.05), but none of the associations obtained marked significance (P,0.01).. A recent multi-locus candidate gene study (702 SNPs in 145 genes), conducted in 408 ...
In this paper we propose a new method to analyze time-to-event data in longitudinal genetic studies. This method address the fundamental problem of incorporating uncertainty when analyzing survival data and imputed single-nucleotide polymorphisms (SNPs) from genome-wide association studies (GWAS). Our method incorporates uncertainty in the likelihood function, the opposite of existing methods that incorporate the uncertainty in the design matrix. Through simulation studies and real data analyses, we show that our proposed method is unbiased and provides powerful results. We also show how combining results from different GWAS (meta-analysis) may lead to wrong results when effects are not estimated using our approach. The model is implemented in an R package that is designed to analyze uncertainty not only arising from imputed SNPs, but also from copy number variants ...
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Presenter: Debbie Nickerson, Ph.D.. Hosts: David Schwartz, M.D., M.P.H. and Samuel Wilson, M.D.. This workshop will provide an overview of the latest approaches for identifying and genotyping single nucleotide polymorphisms (SNPs) and evaluating genetic associations across the human genome. Topics include the extraction of SNP data from public resources, approaches for SNP discovery by re-sequencing, software tools for haplotype inference and optimal SNP selection for genotyping, platform approaches for SNP genotyping, and the analyses of these datasets for genotype-phenotype studies. The workshop will also provide opportunities for hands-on tutorials on a variety of the software tools used for variation analysis.. Registration for the workshop is now closed. There is no charge for the workshop itself; any travel and lodging expenses are the responsibility of the individuals attending the workshop.. ...
Genetic association studies have identified more than a dozen genes associated with risk of pancreatic cancer. Given this genetic heterogeneity, family history can be useful for identifying individuals at high-risk for this disease. The goal of this analysis was to evaluate associations of family history of diabetes and family history of pancreatic cancer with risk of pancreatic cancer. PACIFIC is a case-control study based in two large health plans. Cases were diagnosed with pancreatic ductal adenocarcinoma (PDA) and controls were selected from the health plan enrollment databases and frequency-matched to cases. Family history data were collected using an interviewer-administered questionnaire and were available on 654 cases and 697 controls. Logistic regression was used for the association analyses. First-degree relative history of diabetes was statistically significantly associated with increased risk of PDA (odds ratio (OR): 1.37, 95% confidence interval (CI): 1.10-1.71). The highest risk of ...
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This project sought to identify candidate genes for specific diseases in dogs. Candidate genes are genes known to cause specific diseases in other species. The researchers searched for canine equivalents of three human chromosomes. They identified more than 25 Type I markers (markers that are associated with specific genes). These markers, mapped on the canine genome linkage map, provide valuable information to other scientists looking for the genes causing various heritable diseases in dogs.
Gene-based tests:X,sup,2,/sup,=1.83, P-value = 0.708 in additive model in SZ/SZA, X,sup,2,/sup,=2.214, P-value = 0.73 in dominant model in SZ/SZA, X,sup,2,/sup,=1.351, P-value = 0.908 in recessive model in SZ/SZA.No association was observed using neither single SNP-based analyses nor gene-based tests in SZ/SZA ...
RS24A_SCHPO (O13784 ), RS24A_YEAST (P0CX31 ), RS24B_SCHPO (O59865 ), RS24B_YEAST (P0CX32 ), RS24_AERPE (Q9YCY0 ), RS24_ARCFU (O29151 ), RS24_BOVIN (Q56JU9 ), RS24_CHATD (P0CU28 ), RS24_DICDI (Q75K27 ), RS24_HALLT (B9LSM1 ), RS24_HALMA (P19953 ), RS24_HALS3 (B0R6Y2 ), RS24_HALSA (Q9HNL4 ), RS24_HALWD (Q18KI1 ), RS24_HUMAN (P62847 ), RS24_ICTPU (Q90YQ0 ), RS24_IGNH4 (A8A953 ), RS24_MACFA (Q4R5H5 ), RS24_MESAU (P62848 ), RS24_META3 (A6UTQ0 ), RS24_METAC (Q8TJT2 ), RS24_METJA (P54032 ), RS24_METKA (Q8TVD8 ), RS24_METM5 (A4FZ58 ), RS24_METM6 (A9A6J0 ), RS24_METM7 (A6VJ77 ), RS24_METMA (Q8PZ95 ), RS24_METMP (P61193 ), RS24_METS3 (A5UJM1 ), RS24_METTH (O26367 ), RS24_METVS (A6US52 ), RS24_MOUSE (P62849 ), RS24_MUCCL (P14249 ), RS24_NANEQ (Q74M50 ), RS24_ORYLA (Q9W6X9 ), RS24_PICTO (Q6L0P8 ), RS24_PONAB (Q5RAQ8 ), RS24_PYRAB (Q9UY20 ), RS24_PYRAE (Q8ZV65 ), RS24_PYRFU (Q8U442 ), RS24_PYRHO (P58746 ), RS24_RAT (P62850 ), RS24_SPOFR (Q962Q6 ), RS24_SULAC (Q4JAF9 ), RS24_SULIA (C3N6N7 ), RS24_SULIK (C4KIA8 ...
Genetic, medical, and environmental data on 100,000 Kaiser Permanente enrollees will become accessible to researchers next year. It will be free to those conducting NIH-funded studies, but others will need to pay a fee.
UNIL PhD literature seminar: Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls ...
TY - JOUR. T1 - A 2-stage genome-wide association study to identify single nucleotide polymorphisms associated with development of erectile dysfunction following radiation therapy for prostate cancer. AU - Kerns, Sarah L.. AU - Stock, Richard. AU - Stone, Nelson. AU - Buckstein, Michael. AU - Shao, Yongzhao. AU - Campbell, Christopher. AU - Rath, Lynda. AU - De Ruysscher, Dirk. AU - Lammering, Guido. AU - Hixson, Rosetta. AU - Cesaretti, Jamie. AU - Terk, Mitchell. AU - Ostrer, Harry. AU - Rosenstein, Barry S.. PY - 2013/1/1. Y1 - 2013/1/1. N2 - Purpose: To identify single nucleotide polymorphisms (SNPs) associated with development of erectile dysfunction (ED) among prostate cancer patients treated with radiation therapy. Methods and Materials: A 2-stage genome-wide association study was performed. Patients were split randomly into a stage I discovery cohort (132 cases, 103 controls) and a stage II replication cohort (128 cases, 102 controls). The discovery cohort was genotyped using Affymetrix ...
Background: Crohns disease and ulcerative colitis are the two major forms of inflammatory bowel disease; treatment strategies have historically been determined by this binary categorisation. Genetic studies have identified 163 susceptibility loci for inflammatory bowel disease, mostly shared between Crohns disease and ulcerative colitis. We undertook the largest genotype association study, to date, in widely used clinical subphenotypes of inflammatory bowel disease with the goal of further understanding the biological relations between diseases.. Methods This study included patients from 49 centres in 16 countries in Europe, North America, and Australasia. We applied the Montreal classification system of inflammatory bowel disease subphenotypes to 34,819 patients (19,713 with Crohns disease, 14,683 with ulcerative colitis) genotyped on the Immunochip array. We tested for genotype-phenotype associations across 156,154 genetic variants. We generated genetic risk scores by combining information ...
TY - JOUR. T1 - Genome-wide and gene-based association studies of anxiety disorders in european and african american samples. AU - Otowa, Takeshi. AU - Maher, Brion S.. AU - Aggen, Steven H.. AU - McClay, Joseph L.. AU - Van Den Oord, Edwin J.. AU - Hettema, John M.. PY - 2014/11/12. Y1 - 2014/11/12. N2 - Anxiety disorders (ADs) are common mental disorders caused by a combination of genetic and environmental factors. Since ADs are highly comorbid with each other, partially due to shared genetic basis, studying AD phenotypes in a coordinated manner may be a powerful strategy for identifying potential genetic loci for ADs. To detect these loci, we performed genome-wide association studies (GWAS) of ADs. In addition, as a complementary approach to single-locus analysis, we also conducted gene- and pathway-based analyses. GWAS data were derived from the control sample of the Molecular Genetics of Schizophrenia (MGS) project (2,540 European American and 849 African American subjects) genotyped on the ...
The common variants in the fat mass- and obesity-associated (FTO) gene have been previously found to be associated with obesity in various adult populations. The objective of the present study was to investigate whether the single nucleotide polymorphisms (SNPs) and linkage disequilibrium (LD) blocks in various regions of the FTO gene are associated with predisposition to obesity in Malaysian Malays. Thirty-one FTO SNPs were genotyped in 587 (158 obese and 429 non-obese) Malaysian Malay subjects. Obesity traits and lipid profiles were measured and single-marker association testing, LD testing, and haplotype association analysis were performed. LD analysis of the FTO SNPs revealed the presence of 57 regions with complete LD (D = 1.0). In addition, we detected the association of rs17817288 with low-density lipoprotein cholesterol. The FTO gene may therefore be involved in lipid metabolism in Malaysian Malays. Two haplotype blocks were present in this region of the FTO gene, but no particular ...
Single nucleotide polymorphisms (SNPs) are important markers which can be used in association studies searching for susceptible genes of complex diseases. High-throughput methods are needed for SNP genotyping in a large number of samples. In this study, we applied polyacrylamide gel-based microarray combined with dual-color hybridization for association study of four BDNF polymorphisms with autism. All the SNPs in both patients and controls could be analyzed quickly and correctly. Among four SNPs, only C270T polymorphism showed significant differences in the frequency of the allele (χ2 = 7.809, p = 0.005) and genotype (χ2 = 7.800, p = 0.020). In the haplotype association analysis, there was significant difference in global haplotype distribution between the groups (χ2 = 28.19,p = 3.44e-005). We suggest that BDNF has a possible role in the pathogenesis of autism. The study also show that the polyacrylamide gel-based microarray combined with dual-color hybridization is a rapid, simple and high
Genetic association studies hinge on definite clinical case definitions of the disease of interest. This is why more penetrant mutations were overrepresented in early multiple endocrine neoplasia 2 (MEN2) studies, whereas less penetrant mutations went underrepresented. Enrichment of genetic association studies with advanced disease may produce a flawed understanding of disease evolution, precipitating far-reaching surgical strategies like bilateral total adrenalectomy and 4-gland parathyroidectomy in MEN2. The insight into the natural course of the disease gleaned over the past 25 years caused a paradigm shift in MEN2: from the removal of target organs at the expense of greater operative morbidity to close biochemical surveillance and targeted resection of adrenal tumors and hyperplastic parathyroid glands ...
Exome sequencing will be used as part of a tiered genetic analysis in a large cohort of up to 700 pediatric cardiomyopathy subjects with systolic (dilated cardiomyopathy) or diastolic (hypertrophic or restrictive cardiomyopathy) dysfunction. The biological parent(s) of enrolled participants will also be approached about participating and providing a blood sample for genetic testing. In addition to the parent(s), the participants siblings and other relatives may also be approached regarding enrollment, based on the pedigree and family history.. This study will significantly increase our understanding of pediatric cardiomyopathy by defining the prevalence of mutations in genes known to cause cardiomyopathy as well as identifying novel disease-causing genes in the pediatric population. Genetic association tests will identify variants that modify disease. Novel bioinformatics and systems biology applications for interpretation of exome level genetic information will contribute fundamental knowledge ...
Sequencing of the human genome has recently been completed and mapping of the complete genomic variation is ongoing. During the last decade there has been a huge expansion of studies of genetic variants, both with respect to association studies of disease risk and for studies of genetic factors of prognosis and treatments response, i.e., pharmacogenomics. The use of genetics to predict a patients risk of disease or treatment response is one step toward an improved personalised prevention and screening modality for the prevention of cancer and treatment selection. The technology and statistical methods for completing whole genome tagging of variants and genome wide association studies has developed rapidly over the last decade. After identifying the genetic loci with the strongest, statistical associations with disease risk, future studies will need to further characterise the genotype-phenotype relationship to provide a biological basis for prevention and treatment decisions according to ...
Background Telomerase expression is one of the characteristics of gastric cancer (GC) cells and telomerase activity is frequently up-regulated by a variety of mechanisms during GC development....
I use cutting-edge genomic technologies to understand the impact of human genetic variation and to understand the genetic causes of musculoskeletal disease Rare Variant Associations Since 2009, I have been working to understand the impact of rare genetics variants, both coding and non-coding on complex traits. Read more → Common Variant Associations Using genotyping microarrays and exome sequencing,…
The observed connection between circadian disruption (e.g., shift work) and cancer risk in epidemiologic studies has led to the circadian gene hypothesis, which suggests that genetic variants in genes responsible for maintaining circadian rhythm may affect an individuals susceptibility to human cancers. This hypothesis is supported by results from recent genetic association studies of breast cancer ( 28, 29), prostate cancer ( 24), and NHL ( 5). The findings from the current study of CRY2 provide more evidence demonstrating a role for the circadian genes in NHL susceptibility.. To the best of our knowledge, genetic variants in CRY2 have not been previously examined in NHL, and only one of the SNPs genotyped in the case-control portion of this analysis had been studied previously; in a population-based case-control study conducted in China, which showed a significant association between the variant allele of rs1401417 and increased risk of prostate cancer ( 24). This finding is consistent with ...
Hepatitis C virus (HCV) is commonly seen in the Coachella Valley of Southern California. Genetic Research institute of the Desert (GRID), a nonprofit research center was established in the Coachella valley with a goal to investigate genetic aspects of cancer, as well as infectious and some neurological diseases. This research effort focused on the genetic variants in the HCV group of patients compared to normal healthy individuals. Genetic association could determine the drug responsiveness and aid in treatment; accordingly, a research objective was to determine genetic variants associated with the disease and to find the multiple allelic associations of these genes. The associated genes can be used as prognostic markers, as well as help design drug for hepatitis ...
3.0.CO;2-O. PMID 9514581. Wang YC, Tsai SJ, Liu TY, Liu HC, Hong CJ (January 2001). "No association between tryptophan hydroxylase gene polymorphism and Alzheimers disease". Neuropsychobiology. 43 (1): 1-4. doi:10.1159/000054856. PMID 11150890. Allen NC, Bagade S, McQueen MB, Ioannidis JP, Kavvoura FK, Khoury MJ, Tanzi RE, Bertram L (July 2008). "Systematic meta-analyses and field synopsis of genetic association studies in schizophrenia: the SzGene database". Nat. Genet. 40 (7): 827-34. doi:10.1038/ng.171. PMID 18583979. Li D, He L (2007). "Further clarification of the contribution of the tryptophan hydroxylase (TPH) gene to suicidal behavior using systematic allelic and genotypic meta-analyses". Hum. Genet. 119 (3): 233-40. doi:10.1007/s00439-005-0113-x. PMID 16450114. Nielsen DA, Dean M, Goldman D (1993). "Genetic mapping of the human tryptophan hydroxylase gene on chromosome 11, using an intronic conformational polymorphism". Am. J. Hum. Genet. 51 (6): 1366-71. PMC 1682899 . PMID 1463016. ...
Follow-up studies of eating disorders (EDs) suggest outcomes ranging from recovery to chronic illness or death, but predictors of outcome have not been consistently identified. We tested 5151 single-nucleotide polymorphisms (SNPs) in approximately 350 candidate genes for association with recovery from ED in 1878 women. Initial analyses focused on a strictly defined discovery cohort of women who were over age 25 years, carried a lifetime diagnosis of an ED, and for whom data were available regarding the presence (n = 361 ongoing symptoms in the past year, ie, ill) or absence (n = 115 no symptoms in the past year, ie, recovered) of ED symptoms. An intronic SNP (rs17536211) in GABRG1 showed the strongest statistical evidence of association (p = 4.63 x 10(-6), false discovery rate (FDR) = 0.021, odds ratio (OR) = 0.46). We replicated these findings in a more liberally defined cohort of women age 25 years or younger (n = 464 ill, n = 107 recovered; p = 0.0336, OR = 0.68; combined sample p = 4.57 ...
In 2003, Avshalom Caspi and colleagues published an influential article (Google Scholar lists it as having almost 2000 citations in 6 years) claiming that genetic variation in the seratonin transposter gene influences how people respond to traumatic events--the particular, in terms of risk of depression. For years, this has been the poster-child example of gene-environment interactions (for whatever reason, finding significant interaction terms like this is the Holy Grail of human genetics for some). Like the more recent dubious breastfeeding-IQ-genetics story (led by the same group, it should be noted), the authors identified a phenotype they wished to study (depression), an environmental factor that plays a role in the phenotype (traumatic events), genotyped a couple markers in a gene they thought might reasonably be expected to play a role in that phenotype (seratonin), and found a "statistically significant" interaction. Voila ...
R codes for the (adaptive) Sum of Powered Score (SPU and aSPU) tests, inverse variance weighted Sum of Powered score (SPUw and aSPUw) tests and gene-based and some pathway based association tests (Pathway based Sum of Powered Score tests (SPUpath), adaptive SPUpath (aSPUpath) test, GEEaSPU test for multiple traits - single SNP (single nucleotide polymorphism) association in generalized estimation equations, MTaSPUs test for multiple traits - single SNP association with Genome Wide Association Studies (GWAS) summary statistics, Gene-based Association Test that uses an extended Simes procedure (GATES), Hybrid Set-based Test (HYST) and extended version of GATES test for pathway-based association testing (GATES-Simes). ). The tests can be used with genetic and other data sets with covariates. The response variable is binary or quantitative. Summary; (1) Single trait-SNP set association with individual-level data (aSPU, aSPUw, aSPUr), (2) Single trait-SNP ...
One goal of personal genomics is to use information about genomic variation to predict who is at risk for various common diseases. Technological advances in genotyping have spawned several personal genetic testing services that market genotyping services directly to the consumer. An important goal of consumer genetic testing is to provide health information along with the genotyping results. This has the potential to integrate detailed personal genetic and genomic information into healthcare decision making. Despite the potential importance of these advances, there are some important limitations. One concern is that much of the literature that is used to formulate personal genetics reports is based on genetic association studies that consider each genetic variant independently of the others. It is our working hypothesis that the true value of personal genomics will only be realized when the complexity of the genotype-to-phenotype mapping relationship is embraced, rather than ignored. We focus ...
The epidermis forms a critical barrier that is maintained by orchestrated programs of proliferation, differentiation, and cell death. Gene mutations that disturb this turnover process may cause skin diseases. Human GASDERMIN A (GSDMA) is frequently silenced in gastric cancer cell lines and its overexpression has been reported to induce apoptosis. GSDMA has also been linked with airway hyperresponsiveness in genetic association studies. The function of GSDMA in the skin was deduced by dominant mutations in mouse gasdermin A3 (Gsdma3), which caused skin inflammation and hair loss. However, the mechanism for the autosomal dominance of Gsdma3 mutations and the mode of Gsdma3s action remain unanswered. We demonstrated a novel function of Gsdma3 in modulating mitochondrial oxidative stress. We showed that Gsdma3 is regulated by intramolecular fold-back inhibition, which is disrupted by dominant mutations in the C-terminal domain. The unmasked N-terminal domain of Gsdma3 associates with Hsp90 and is delivered
There is a spectrum of involvement in those with the FMR1 premutation that ranges from developmental problems in childhood and psychopathology in adulthood to n...
Quantitative abnormalities of the von Willebrand factor-factor VIII (VWF-FVIII) complex associate with inherited bleeding or thrombotic disorders. Receptor-mediated interactions between plasma VWF-FVIII and phagocytic or immune cells can influence their hemostatic and immunogenic activities. Genetic association studies have demonstrated that variants in the STAB2 gene, which encodes the scavenger receptor stabilin-2, associate with plasma levels of VWF-FVIII. However, the mechanistic basis and pathophysiological consequences of this association are unknown. We have demonstrated that stabilin-2-expressing cells bind and internalize human VWF and FVIII in a VWF-dependent manner, and stabilin-2-deficient mice displayed prolonged human VWF-FVIII half-life compared with controls. The stabilin-2 variant p.E2377K significantly decreased stabilin-2 expression and impaired VWF endocytosis in a heterologous expression system, and common STAB2 variants associated with plasma VWF levels in type 1 von ...
Last month I pointed to a paper on Chinese population structure, Genomic Dissection of Population Substructure of Han Chinese and Its Implication in Association Studies. One to note was that the average FST differentiation Han populations was on the order of 0.002, while those differentiating Europeans was on the order of 0.009. Below are the various Han population, along with Japanese. CHB = Beijing, while CHD = Denver. The Denver sample is probably biased toward Cantonese and Fujianese, since most American Chinese are from these two groups. As a point of reference, here are South Asian genetic distances. ...
Wang HM, Zhang XY, Jin B. TERT genetic polymorphism rs2736100 was associated with lung cancer: a meta-analysis based on 14,492 subjects. Genetic Testing and Molecular Biomarkers 2013; 17(12): 937- ...
The correlation of phenotypic outcomes with genetic variation and environmental factors is a core pursuit in biology and biomedicine. Numerous challenges impede our progress: patient phenotypes may not match known diseases, candidate variants may be in genes that have not been characterized, model organisms may not recapitulate human or veterinary diseases, filling evolutionary gaps is difficult, and many resources must be queried to find potentially significant genotype-phenotype associations. Non-human organisms have proven instrumental in revealing biological mechanisms.