• Causal inference via Mendelian randomization requires making strong assumptions about horizontal pleiotropy, where genetic instruments are connected to the outcome not only through the exposure. (nature.com)
  • Mendelian randomization estimates from each genetic instrument were combined using inverse variance weighted meta-analysis, with alternate methods (eg, weighted median, MR Egger, MR-Pleiotropy Residual Sum and Outlier [PRESSO]) and multiple sensitivity analyses to assess horizontal pleiotropy and remove outliers. (bestfutureyou.com)
  • After correcting the heterogeneity and horizontal pleiotropy, the results indicated that patients with SS were significantly associated with an increased risk of lymphomas (odds ratio [OR] = 1.0010, 95% confidence interval [CI]: 1.0005-1.0015, P = 0.0002) and reduced risks of prostate cancer (OR = 0.9972, 95% CI: 0.9960-0.9985, P = 2.45 × 10 −5 ) and endometrial cancer (OR = 0.9414, 95% CI: 0.9158-0.9676, P = 1.65 × 10 −5 ). (biomedcentral.com)
  • Linkage disequilibrium score regression and Mendelian Randomization (MR) analyses were applied to investigate shared genetic mechanisms (horizontal pleiotropy) and causal relationships (mediated pleiotropy) among these traits. (biorxiv.org)
  • these associations were largely consistent in sensitivity analyses accounting for horizontal pleiotropy. (exeter.ac.uk)
  • Sensitivity analysis of the two candidate genera and metabolites using the MR-Egger and weighted-median methods produced similar estimates, and no horizontal pleiotropy or outliers were observed. (biomedcentral.com)
  • The Cochran's Q test, MR-Egger intercept test, and leave-one-out sensitivity analyses were used to assess the heterogeneities, horizontal pleiotropy, and stabilities of SNPs in endometriosis. (biomedcentral.com)
  • 1) the selected instruments must be associated with the exposure, (2) the instruments must not be associated with confounding factors, and (3) the instruments must influence the outcome only through the exposure (no horizontal pleiotropy exists). (biomedcentral.com)
  • Causal inference from observational data is a fundamental objective that has been receiving increasing attention in multiple domains including biology, epidemiology, and economics. (nature.com)
  • Graphical models are a cornerstone of causal inference as they explicitly describe the generating process of the observed data. (nature.com)
  • Due to their size and depth, these datasets offer new opportunities for discovery and inference of causal relationships between traits. (nature.com)
  • Sensitivity analyses for robust causal inference from mendelian randomization analyses with multiple genetic variants. (nature.com)
  • Findings In this 2-sample mendelian randomization study using genetic instruments from large-scale genome-wide association studies to support potential causal inference, higher levels of physical activity (indexed by objective accelerometer data) were linked to reduced odds for major depression. (bestfutureyou.com)
  • Objective To examine bidirectional relationships between physical activity and depression using a genetically informed method for assessing potential causal inference. (bestfutureyou.com)
  • This finding of widespread pleiotropy has implications for artificial selection in agriculture, interpretation of phenotypic correlations, social inequality, attempts to use Mendelian randomization in causal inference, the understanding of the biological origins of complex traits, and the design of GWASes. (wikipedia.org)
  • These types of blended conclusions motivate the need for a leading-pushed causal inference data out-of lipids towards BC. (cristonautas.com)
  • In regard to causal inference, observational studies may be biased by confounding factors and reverse causality. (biomedcentral.com)
  • Here we investigate the associations of maternal quitting, reducing, and continuing smoking during pregnancy with longitudinal fetal growth by triangulating evidence from 3 analytical approaches to strengthen causal inference. (plos.org)
  • On 96 complex traits from 337,198 subjects from the UK Biobank, our results cover expected causal links and many new ones that were previously suggested by correlation-based observational studies. (nature.com)
  • In our recently published research , we found that the genetic links between traits found in many studies might not be connected by genes at all. (inverse.com)
  • With a clearer understanding of the genetic basis of different traits, scientists would be better able to determine risk factors for related diseases. (inverse.com)
  • Because the genes you inherit from your parents remain unchanged throughout your life (with rare exceptions), it makes sense to assume that there is a causal relationship between certain traits you have and your genetics. (inverse.com)
  • Researchers have run thousands of GWAS to date , identifying genetic variants associated with myriad diseases and disease-related traits. (inverse.com)
  • This form of biological overlap, in which the same genes are thought to influence several apparently unrelated traits, is known as pleiotropy . (inverse.com)
  • Here, geneticists investigate whether the genes associated with a given trait are associated with other traits or diseases by statistically analyzing large samples of genetic data. (inverse.com)
  • Scientists use the findings from genetic correlation analyses to figure out the potential shared causes of these traits. (inverse.com)
  • In multivariate quantitative genetics, a genetic correlation (denoted r g {\displaystyle r_{g}} or r a {\displaystyle r_{a}} ) is the proportion of variance that two traits share due to genetic causes, the correlation between the genetic influences on a trait and the genetic influences on a different trait estimating the degree of pleiotropy or causal overlap. (wikipedia.org)
  • A genetic correlation of 0 implies that the genetic effects on one trait are independent of the other, while a correlation of 1 implies that all of the genetic influences on the two traits are identical. (wikipedia.org)
  • Genetic correlations have applications in validation of genome-wide association study (GWAS) results, breeding, prediction of traits, and discovering the etiology of traits & diseases. (wikipedia.org)
  • a genetic correlation between two traits can contribute to the observed (phenotypic) correlation between two traits, but genetic correlations can also be opposite observed phenotypic correlations if the environment correlation is sufficiently strong in the other direction, perhaps due to tradeoffs or specialization. (wikipedia.org)
  • two traits could be both highly heritable but not be genetically correlated or have small heritabilities and be completely correlated (as long as the heritabilities are non-zero). (wikipedia.org)
  • These two traits may individually have a very high heritability (most of the population-level variation in the trait due to genetic differences, or in simpler terms, genetics contributes significantly to these two traits), however, they may still have a very low genetic correlation if, for instance, these two traits were being controlled by different, non-overlapping, non-linked genetic loci. (wikipedia.org)
  • A genetic correlation between two traits will tend to produce phenotypic correlations - e.g. the genetic correlation between intelligence and SES or education and family SES implies that intelligence/SES will also correlate phenotypically. (wikipedia.org)
  • This can be an important constraint on conceptualizations of the two traits: traits which seem different phenotypically but which share a common genetic basis require an explanation for how these genes can influence both traits. (wikipedia.org)
  • METHODS: We examined the association of these genetically predicted adiposity-related traits with risk of prostate cancer overall, aggressive and early onset disease using outcome summary statistics from the PRACTICAL consortium (including 15,167 aggressive cases). (exeter.ac.uk)
  • Polygenic scores create the potential for existing embryo selection technologies to be used to select for a wider range of predicted genetically influenced characteristics including continuous traits. (bmj.com)
  • Polygenic risk scores or polygenic scores (PS) analyse an individual's genome, aggregating thousands of genes, to estimate genetic tendency towards particular traits and diseases. (bmj.com)
  • We aimed to systematically assess the causal associations between childhood body mass index (BMI) and various adult traits/diseases using two-sample Mendelian randomization (MR). (biomedcentral.com)
  • We identified potential causal effects of childhood obesity on 60 adult traits (27 disease-related traits, 27 lifestyle factors, and 6 other traits). (biomedcentral.com)
  • With a large amount of GWAS summary data deposited in public databases, two-sample MR analysis provides a cost-efficient way to investigate the potential causal effects of childhood obesity on adult traits. (biomedcentral.com)
  • Design, Setting, and Participants This 2-sample mendelian randomization (MR) used independent top genetic variants associated with 2 physical activity phenotypes-self-reported (n = 377 234) and objective accelerometer-based (n = 91 084)-and with major depressive disorder (MDD) (n = 143 265) as genetic instruments from the largest available, nonoverlapping genome-wide association studies (GWAS). (bestfutureyou.com)
  • Conclusions and Relevance Using genetic instruments identified from large-scale GWAS, robust evidence supports a protective relationship between objectively assessed-but not self-reported-physical activity and the risk for MDD. (bestfutureyou.com)
  • Our GWAS of health-records derived VMS identified a genetic signal near TACR3 associated with a lower risk of VMS (OR=0.76 (95% CI 0.72,0.80) per A allele, P =3.7x10 -27 ), which was consistent with previous studies, validating this approach. (biomedcentral.com)
  • Additionally, population-based genome-wide association studies (GWAS) have identified several more common genetic variants in or near the TACR3 gene associated with normal variation in age at menarche [ 16 ]. (biomedcentral.com)
  • Therefore, the purpose of this study is to use publicly available GWAS summary statistics to examine the causal relationship between coagulation factors and the risk of endometriosis. (biomedcentral.com)
  • Our MR analysis based on GWAS data from large-scale population studies demonstrated the causal associations between ADAMTS13/vWF and the risk of endometriosis. (biomedcentral.com)
  • Here we utilise GWAS summary statistics to study the shared genetic influences (pleiotropy) between severe COVID-19 and 344 blood analytes at the genome, gene and single nucleotide polymorphism levels. (cdc.gov)
  • Lee JJ, McGue M, Iacono WG, Michael AM, Chabris CF. The causal influence of brain size on human intelligence: evidence from within-family phenotypic associations and GWAS modeling. (beingmedicos.com)
  • Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors. (nature.com)
  • We used the bivariate causal mixture model (MiXeR) to quantify genome-wide polygenic overlap and the conditional/conjunctional false discovery rate (pleioFDR) method to identify shared loci, based on genome-wide association study summary statistics on depression (n = 450,619), coronary artery disease (n = 502,713) and nine cardiovascular risk factors (n = 204,402-776,078). (plos.org)
  • Genetic loci were functionally annotated using FUnctional Mapping and Annotation (FUMA). (plos.org)
  • We previously identified associations with ovarian cancer outcome at five genetic loci. (escholarship.org)
  • To identify putatively causal genetic variants and target genes, we prioritized two ovarian outcome loci (1q22 and 19p12) for further study. (escholarship.org)
  • The associations remained consistent in sensitivity analyses, and no evidence of pleiotropy was detected. (nature.com)
  • Results were broadly consistent in sensitivity analyses using simple and weighted-median approaches accounting for potential genetic pleiotropy. (bmj.com)
  • The sensitivity and specificity of the SGTF signature was 99.6% (95% CI 96.1-99.9%) and 98.6% (95% CI 99.2-99.8%) for the Alpha variant and 99.6% (95% CI 98.9-99.9%) and 99.8% (95% CI 99.4-99.9%) for the Omicron variant. (cdc.gov)
  • After primary analysis and a series of sensitivity analyses, 17 metabolites were identified from UK Biobank that have a causal relationship with five infections. (biomedcentral.com)
  • Results were robust to sensitivity analyses examining pleiotropy (including weighted-median-MR, MR-Egger). (uni-koeln.de)
  • To examine the causal associations of diet-derived circulating antioxidants with knee osteoarthritis (OA), hip OA, and rheumatoid arthritis (RA) within the two-sample Mendelian randomization (MR) framework. (frontiersin.org)
  • We aimed to examine the causal associations of IR with cardiovascular diseases, including coronary artery disease, myocardial infarction, ischemic stroke and its subtypes, using Mendelian randomization. (bmj.com)
  • With the plethora of new genes being identified, genetic rather than phenotype-based classification of Mendelian diseases such as spinocerebellar ataxia (SCA), hereditary spastic paraplegia (HSP) and Charcot-Marie-Tooth disease (CMT) has become widely accepted. (biomedcentral.com)
  • Possible mechanisms of pleiotropy include different downstream effects of different mutations in the same gene, presence of modifier genes, and oligogenic inheritance. (biomedcentral.com)
  • In 2013, Dylan began working at QIMR Berghofer and has undertaken the functional follow-up of large-scale genetic studies of breast, endometrial and ovarian cancer to identify the likely causal variants and genes that mediate associations with cancer risk and survival. (edu.au)
  • There was no evidence of pleiotropy. (bmj.com)
  • We used Mendelian randomization (MR) to evaluate whether genetic evidence supports a causal role for PUFAs on overall cancer outcomes. (aacrjournals.org)
  • No evidence of the causal relationship was observed for cancers on SS. (biomedcentral.com)
  • SS had significant causal relationships with lymphomas, prostate cancer, and endometrial cancer, and suggestive evidence of association was found in liver and bile duct cancer and cancer of urinary tract, indicating that SS may play a vital role in the incidence of these malignancies. (biomedcentral.com)
  • There was no strong evidence that genetically determined UFA, FA or BMI were associated with overall prostate cancer or early age of onset prostate cancer. (exeter.ac.uk)
  • There is strong epidemiologic and laboratory evidence for a causal association between new variant CJD and BSE. (nationalacademies.org)
  • Six analytes (alanine aminotransferase, alkaline phosphatase, apolipoprotein B, C-reactive protein, triglycerides, and urate) display evidence of pleiotropy with severe COVID-19 at all three levels. (cdc.gov)
  • However, there was no evidence of a causal connection between blood metabolites and the risk of URTI or SSTI, indicating a need for larger-scale studies to further investigate susceptibility to certain infection phenotypes. (biomedcentral.com)
  • In the absence of a randomized controlled trial (RCT) or the initiation of a new RCT, the approach is an important alternative strategy that can provide reliable evidence of a causal relationship between exposure and disease risk [ 9 ]. (biomedcentral.com)
  • Conclusions The previously observed J shaped relation between BMI and risk of all cause mortality appears to have a causal basis, but subgroup analyses by smoking status revealed that the BMI-mortality relation is likely comprised of at least two distinct curves, rather than one J shaped relation. (bmj.com)
  • This study used openly available software and code, specifically LD-score regression [ https://github.com/bulik/ldsc/ ] (if we report genetic correlation), MiXer ( https://github.com/precimed/mixer ) and conjunctional FDR [ https://github.com/precimed/pleiofdr/ ]. (plos.org)
  • One way scientists assess pleiotropy is through genetic correlation analysis . (inverse.com)
  • Over the past decade, genetic correlation analysis has become the primary method for assessing potential pleiotropy across fields as diverse as internal medicine , social science , and psychiatry . (inverse.com)
  • We wanted to find out how much the assumption of random mating affects the accuracy of genetic correlation analyses. (inverse.com)
  • Genetic correlation models were introduced into behavioral genetics in the 1970s-1980s. (wikipedia.org)
  • The phenotypic correlation will be limited by the degree of genetic correlation and also by the heritability of each trait. (wikipedia.org)
  • The expected phenotypic correlation is the bivariate heritability' and can be calculated as the square roots of the heritabilities multiplied by the genetic correlation. (wikipedia.org)
  • The observation of pleiotropy has emerged, with mutations in the same gene giving rise to diverse phenotypes, which further increases the complexity of phenotype-genotype correlation. (biomedcentral.com)
  • Outcomes Positive genetic correlation was observed between MD and AD (rg MD-AD =+0.47, P =6.6×10 -10 ). (biorxiv.org)
  • We identified genetic instruments for six PUFAs from previous literature and evaluated their association with overall cancer risk (46,155 cases, 270,342 controls) and cancer mortality (6,998 deaths, 270,342 controls) among the UK Biobank cohort. (aacrjournals.org)
  • We used logistic regression to identify associations between different vitamin D variables (25-hydroxyvitamin D concentration (25-OHD), ambient UVB and genetically-predicted 25-OHD concentrations) and COVID-19 (risk of infection, hospitalisation and death) in 495,780 participants from UK Biobank. (medrxiv.org)
  • Our two-sample MR analysis of 11 coagulation factors in the UK Biobank suggested a reliable causal effect of genetically predicted plasma ADAMTS13 level on decreased endometriosis risk. (biomedcentral.com)
  • Genetic instruments were single nucleotide polymorphisms (SNPs) associated in UK Biobank with wrist-worn accelerometer-measured overall physical activity (n(snps)=5) or sedentary time (n(snps)=6), or accelerometer-measured (n(snps)=1) or self-reported (n(snps)=5) vigorous physical activity. (uni-koeln.de)
  • Similarly, there may be gene variants that play a role in whether or not someone has schizophrenia. (inverse.com)
  • The advent of next generation sequencing (NGS) has allowed for a system-wide, unbiased approach to identify all gene variants in the genome simultaneously. (biomedcentral.com)
  • It has also become clear that gene variants play a role in common and predominantly sporadic neurodegenerative diseases such as Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS). (biomedcentral.com)
  • Future directions include development of bioinformatics tools and establishment of more extensive public genotype/phenotype databases to better distinguish deleterious gene variants from benign polymorphisms, translation of genetic findings into pathogenic mechanisms through in-vitro and in-vivo studies, and ultimately finding disease-modifying therapies for neurodegenerative disorders. (biomedcentral.com)
  • [9] Although over 200 gene variants have been associated with longevity according to a US-Belgian-UK research database of human genetic variants [10] these explain only a small fraction of the heritability. (wikipedia.org)
  • We used the statistical methods the bivariate causal mixture model (MiXeR) and the conditional/conjunctional false discovery rate (pleioFDR) to quantify genome-wide overlap and to identify shared genetic variants. (plos.org)
  • We found extensive genetic overlap. (plos.org)
  • We also identified 79 unique genomic variants associated with depression and coronary artery disease or the risk factors. (plos.org)
  • We provide support for TACR3 in the genetic basis of VMS but unexpectedly find that rare genomic variants predicted to lower NK3R levels did not modify VMS, despite the proven efficacy of NK3R antagonists. (biomedcentral.com)
  • We conducted a Mendelian randomization study to clarify whether genetically predicted coffee and tea consumption has a causal effect on IA and its subtypes. (nature.com)
  • Since the causal associations between WBC subtypes and HCC risk have not been thoroughly investigated, identifying host factors predisposing individuals to HCC is urgently needed to improve primary prevention and develop treatment strategies. (biomedcentral.com)
  • Our present study attempted to use MR analysis to identify SNPs strongly related to blood WBC subtype counts to evaluate the causal association between WBC subtypes and HCC risk. (biomedcentral.com)
  • Polygenic risk scores (PRS) which summarize individuals' genetic risk profile may enhance targeted colorectal cancer screening. (kaiserpermanente.org)
  • However, genetically defined population subgroups may have increased susceptibility to smoking-related effects on colorectal cancer. (kaiserpermanente.org)
  • Virtually all the statistical methods researchers commonly use to assess genetic correlations assume that mating is random . (inverse.com)
  • We aimed to use Mendelian randomisation (MR) and specific genetic variants to separately test the causal roles of higher adiposity with and without its adverse metabolic effects on diseases.Methods:We selected 37 chronic diseases associated with obesity and genetic variants associated with different aspects of excess weight. (exeter.ac.uk)
  • Inverse-variance weighted, MR-Egger, weighted median, and weighted mode methods were used to estimate the causal effects. (biomedcentral.com)
  • In a subset of this cohort ( n = 39,356), we analysed exome-sequencing data to test the association with VMS of rare deleterious genetic variants. (biomedcentral.com)
  • Genome-wide association study identifies a sequence variant within the DAB2IP gene conferring susceptibility to abdominal aortic aneurysm. (jamanetwork.com)
  • We have identified novel T2DM-susceptibility variants in the African-American population. (kb.se)
  • 2. Genetic susceptibility for major depressive disorder associates with trajectories of depressive symptoms across childhood and adolescence. (massgeneral.org)
  • Testosterone products are prescribed to males for a variety of possible health benefits, but causal effects are unclear. (elifesciences.org)
  • Nevertheless, the causal relationships remain unclear. (biomedcentral.com)
  • however, it is unclear if these associations are causal. (kaiserpermanente.org)
  • cGAUGE also uses ExSep (Exposure-based Separation), a novel test for the existence of causal pathways that does not require selecting instruments. (nature.com)
  • Our results demonstrated that genetically determined lifelong higher exposure to absolute circulating levels of retinol is associated with a decreased risk of hip OA. (frontiersin.org)
  • To attempt to look after these types of discrepancies, latest studies have used the fresh new design off Mendelian randomization (MR) to choose if genetically elevated lipid profile relate with BC exposure. (cristonautas.com)
  • Mendelian randomization (MR), which uses genetic markers of the exposure as instruments, is now widely used to assess the causal relationship between exposure and outcome [ 7 ]. (biomedcentral.com)
  • Even in diseases that are hereditary with a clear genetic contribution, the clinical diagnosis remains difficult due to significant heterogeneity both in clinical features and genetic causes. (biomedcentral.com)
  • Possible mechanisms of pleitropy and future directions to help translate genetic findings to therapeutic interventions will be discussed. (biomedcentral.com)
  • The inverse variance weighted (IVW) method was used to estimate the causal effects. (biomedcentral.com)
  • The purpose of this study was to determine if the variability observed in this behavioural characteristic has an additive genetic component and if so, to estimate heritability (h2). (researchgate.net)
  • In this review, we will discuss the role of genetic variants in hereditary and sporadic neurodegenerative disorders and the insights to etiology and pathogenic mechanisms afforded by advances in genetic sequencing and analysis. (biomedcentral.com)
  • Our pleiotropy analyses genetically link blood levels of 71 analytes to severe COVID-19 in at least one of the three levels of investigation-suggesting shared biological mechanisms or causal relationships. (cdc.gov)
  • Although the mechanisms responsible are understood poorly ( Armstrong, 2001 ), genetic factors are known or suspected to be involved. (frontiersin.org)
  • While genetic factors are known to play a role in periodontitis, a lot of research still needs to be done to understand the precise mechanisms involved. (efp.org)
  • The resulting data set enables additional detailed investigations of genetic pathways underlying psychiatric illnesses in the Brisbane Longitudinal Twin Study (BLTS). (cambridge.org)
  • and (5) heritability estimated on dam components is hD2=0.46, which implies that the maternal effect (genetic and environmental) is an important factor in this type of behaviour.It is concluded that there is an additive genetic, and therefore, hereditary factor for dominant-aggressive behaviour in the English Cocker Spaniel. (researchgate.net)
  • Hereditary DNA sequence variants play a role in the transmission of disease risk in almost all of them (Basson et al. (springer.com)
  • Genetically predicted insulin resistance phenotypes was associated with an increased risk of coronary artery diseases, myocardial infarction, ischemic stroke and the small-artery occlusion subtype of stroke. (bmj.com)
  • The genetic relationship between depression and these cardiovascular phenotypes is not known. (plos.org)
  • The MR analyses also identified potential causal effects of ADAMTS13 and vWF on different sub-phenotypes of endometrioses. (biomedcentral.com)
  • Univariable and multivariable Mendelian randomization (MR) was commandeered to elucidate the causal relationship between blood metabolism and five high-frequency infection phenotypes: sepsis, pneumonia, upper respiratory tract infections (URTI), urinary tract infections (UTI), and skin and subcutaneous tissue infection (SSTI). (biomedcentral.com)
  • However, the phenotypes AgP and CP may not be as distinct as previously assumed and thus may not really be separate entities, because they do share genetic and other risk factors. (efp.org)
  • It is unknown if shared genetic factors contribute to these associations. (plos.org)
  • Using genomics we demonstrate changes in genetic associations with HRT use over time, arising from a change in clinical practice since the early 2000s, which is likely to reflect a switch from preventing post-menopausal complications in women with earlier menopause to primarily treating VMS. (biomedcentral.com)
  • Background Despite established clinical associations among major depression (MD), alcohol dependence (AD), and alcohol consumption (AC), the nature of the causal relationship between them is not completely understood. (biorxiv.org)
  • In the meta-analysis, the causal associations remained significant with a strong effect size. (biomedcentral.com)
  • In this study, we aimed to examine the association between vitamin D and COVID-19 risk and outcomes, and to explore potential causal effects. (medrxiv.org)
  • Mendelian Randomization (MR) is an increasingly prevalent analytical technique that has been extensively employed to deduce the causal impact of exposures on outcomes [ 8 ]. (biomedcentral.com)
  • Summary statistics of genetic instruments associated with knee OA, hip OA, and RA were obtained from corresponding genome-wide association studies (GWASs). (frontiersin.org)
  • Genetic variants associated with coffee and tea consumption (cups/day) were obtained from large genome-wide association studies (GWASs), up to 349,376 subjects. (nature.com)
  • Previous large-scale genome-wide association studies carried out in largely healthy individuals have identified thousands of variants associated with HT, which have then been used to develop multi-ancestry polygenic trait scores (PTS). (haematologica.org)
  • Identification of common genetic risk variants for autism spectrum disorder. (beingmedicos.com)
  • How can researchers be sure that a particular trait or disease is truly genetically linked and not caused by something else? (inverse.com)
  • In many instances, researchers have identified genetic variants that affect more than one trait. (inverse.com)
  • 2021 ), the desired but as yet unmet goal is now to identify DNA sequence variants responsible for trait variation in patients (Klasberg et al. (springer.com)
  • Independent single-nucleotide polymorphisms (SNPs) significantly associated with circulating levels of diet-derived antioxidants (retinol, β-carotene, lycopene, vitamin C and vitamin E) were extracted as genetic instruments. (frontiersin.org)
  • Genetic polymorphisms range in size from single nucleotides (SNPs) to large scale insertions, deletions, or rearrangements that span several millions of base pairs [ 1 , 2 ]. (biomedcentral.com)
  • Here, we present causal Graphical Analysis Using Genetics (cGAUGE), a pipeline that overcomes these limitations using instrument filters with provable properties. (nature.com)
  • She also researches the genetics of favourable adiposity - identifying genetic factors associated with higher fat mass but lower risk of heart disease, and establishing whether or not these genetic factors are associated with less fat in the organs and more under the skin. (exeter.ac.uk)
  • The mission of the Psychiatric & Neurodevelopmental Genetics Unit Mass General is to identify and characterize the genetic basis of psychiatric, behavioral and neurodevelopmental disorders and to translate these discoveries to improvements in clinical care and public health. (massgeneral.org)
  • No other causal association was found. (frontiersin.org)
  • Fig. 2: Association of genetically predicted coffee consumption with intracranial aneurysm. (nature.com)
  • Fig. 3: Association of genetically predicted coffee consumption with aneurysmal subarachnoid hemorrhage. (nature.com)
  • Linear mendelian randomisation analyses indicated an overall positive association between genetically predicted BMI and the risk of all cause mortality. (bmj.com)
  • Whether this reflects a causal association remains to be established. (bmj.com)
  • Conditional analyses demonstrated independence of genetic signals for puberty timing and VMS at the TACR3 locus, including a rare variant predicted to reduce functional NK3R levels that was associated with later menarche ( P = 5 × 10 -9 ) but showed no association with VMS ( P = 0.6). (biomedcentral.com)
  • The apparent positive association of the genetic instrument with fetal growth in non-smokers suggests that genetic pleiotropy may have masked a stronger association in smokers. (plos.org)
  • Association of genetic and environmental factors with autism in a 5-country cohort. (beingmedicos.com)
  • Objective To investigate the shape of the causal relation between body mass index (BMI) and mortality. (bmj.com)
  • To investigate the causal relationship between coagulation factors and the risk of endometriosis, a two-sample Mendelian randomization (MR) analytic framework was used. (biomedcentral.com)
  • Key Points Question Does physical activity have a potential causal role in reducing risk for depression? (bestfutureyou.com)
  • Our study demonstrates that integrating routinely-collected primary care health records and genomic data offers great potential for exploring the genetic basis of symptoms. (biomedcentral.com)
  • Because genetic variations are randomly inherited from parents to offspring during pregnancy, these genetic variations are unlikely to be affected by potential confounding factors and reverse causality. (biomedcentral.com)
  • Follow-up studies testing the causal role of the intestinal microbiota how can i buy pradaxa is regulated by gender and the potential benefits of microbial colonization in early life may be a long way off, but perhaps this line of inquiry. (thebritishbottlecompany.com)
  • For example, certain variants of the PAH gene can have several distinct effects , including altering skin pigmentation and causing seizures. (inverse.com)
  • investigated the effects of naturally produced testosterone using Mendelian randomization, which mimics randomized trials by exploiting the fact that parents randomly pass on their unique genetic variants to their children at conception. (elifesciences.org)
  • Additional MR analysis indicated that causal effects between SS and cancers were not mediated by the well-accepted risk factors of cancers. (biomedcentral.com)
  • These genetic variants included those associated with metabolically 'favourable adiposity' (FA) and 'unfavourable adiposity' (UFA) that are both associated with higher adiposity but with opposite effects on metabolic risk. (exeter.ac.uk)
  • At 1q22, putative regulatory elements enhanced MEF2D promoter activity and haplotypes containing candidate outcome variants modulated these effects. (escholarship.org)
  • Further MR study with more genetic instruments for absolute circulating levels of antioxidants are needed to confirm our results. (frontiersin.org)
  • We are statistical geneticists who study the genetic and nongenetic factors that influence human variation. (inverse.com)
  • This random assignment of genetic variants leads to its informal namesake, "nature's clinical trial", and provides the ability to study cause-and-effect for any genetically determined factors, such as testosterone levels. (elifesciences.org)
  • We subsequently performed a Mendelian Randomisation (MR) study to test if there was any causal effect. (medrxiv.org)
  • We analysed data from 8,621 European liveborn singletons in 2 population-based pregnancy cohorts (the Generation R Study, the Netherlands 2002-2006 [ n = 4,682]) and the Born in Bradford study, United Kingdom 2007-2010 [ n = 3,939]) with fetal ultrasound and birth anthropometric measures, parental smoking during pregnancy, and maternal genetic data. (plos.org)
  • In this MR study, we demonstrated a causal relationship between blood metabolites and the risk of developing sepsis, pneumonia, and UTI. (biomedcentral.com)
  • Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1. (jamanetwork.com)
  • Variants associated with increased risk for depression also increased the risk of coronary artery disease, some of the lipids and c-reactive protein levels, while there was a mixed pattern of direction for the other risk factors. (plos.org)
  • Protein engineering holds great promise for a wide range of human endeavors, such as the development of therapeutics drugs and gene editing, through producing protein variants that enhance the original function or are entirely novel [1]. (gatech.edu)
  • Funding: This work was supported by results in multiple model organisms has provided strong support for a causal role of the manuscript. (thebritishbottlecompany.com)
  • EXPERT VIEW: What is the extent of the role played by genetic factors in periodontitis? (efp.org)
  • Within the domain of genetic risk factors for periodontitis, not only do certain genetic variations play a role, epigenetic changes in DNA are also involved. (efp.org)
  • This was particularly striking at the Duffy/DARC locus, where we observed an epistatic interaction between the SCD genotype and the Duffy null variant (rs2814778) that led to a two-fold weaker effect on neutrophil count. (haematologica.org)
  • No causal effect of SS on other cancer types was detected. (biomedcentral.com)
  • A negative causal effect of ADAMTS13 and a positive causal effect of vWF on endometriosis were observed in the FinnGen. (biomedcentral.com)
  • In the discovery dataset, multivariable MR analysis revealed that sum basophil neutrophil counts had an independent causal effect on the occurrence of HCC, with the sum basophil neutrophil counts as follows: (OR = 0.437, P = 0.003, CI 0.252-0.757). (biomedcentral.com)
  • Algorithms for causal discovery identify patterns of conditional independencies (CI) with theoretical justification for refuting candidate models that are unlikely to have generated the observed data. (nature.com)
  • Univariable and multivariable MR analyses were used to identify risk factors genetically associated with HCC risks. (biomedcentral.com)
  • Mendelian randomization (MR) estimates were calculated with inverse-variance weighted, simple and weighted-median approaches and MR-Egger regression was used to explore pleiotropy. (bmj.com)
  • Genetic predisposition to metabolically unfavourable adiposity and prostate cancer risk: a Mendelian randomization analysis. (exeter.ac.uk)
  • Further analyses identified shared genetic variants found in metabolism of alpha-linolenic pathway for type 2 diabetes. (plos.org)
  • Periodontitis is a complex chronic inflammatory disease, in which there are multiple causal components 1 that play their aetiological roles simultaneously and interact with each other. (efp.org)
  • We evaluated the accuracy of the SGTF signature in identifying these two variants through analysis of all positive SARS-CoV-2 samples tested on the TaqPath RT-PCR and sequenced by next generation sequencing between December 2020 to July 2022. (cdc.gov)
  • Genetic analysis of intellectual disability and autism. (beingmedicos.com)
  • A global reference for human genetic variation. (nature.com)
  • In contrast, we found that a simple PTS for HbF that includes only six variants explained a large fraction of the phenotypic variation (20.5-27.1%), associated with acute chest syndrome and stroke risk, and improved the statistical modeling of the vaso-occlusive crisis rate. (haematologica.org)
  • Between-individual genetic variation is the substrate for selection. (biomedcentral.com)
  • You off epidemiological and clinical test knowledge yet provides yet to decide if or not there can be a beneficial causal relationships anywhere between cholesterol and you can BC. (cristonautas.com)
  • AgP occurs most often at a younger age (up to 35 years old) and these cases involve more genetic risk factors than CP cases (see Fig. 2). (efp.org)
  • This has helped researchers to focus on well-described case-control studies, something that is much needed in the search for genetic risk factors. (efp.org)
  • On the basis of epidemiological studies of twins and families with a higher rate of AgP, it can be concluded that in the younger patients the genetic contribution may account for as much as 50% of causal factors, while in the older patients a genetic contribution of at most 25% has been estimated. (efp.org)
  • Bioinformatic and functional genetic analyses indicated that MEF2D and ZNF100 are targets of candidate outcome variants at 1q22 and 19p12, respectively. (escholarship.org)