SynthesisAmerican journal of human genetics2012
A multi-SNP locus-association method reveals a substantial fraction of the missing heritability.
Synthesis in American journal of human genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Gene-based meta-analysis of genome-wide association studies implicates new loci involved in obesity.Human molecular genetics · 2015Pooled it
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- A Donor Registry: Genomic Analyses ofEcology and evolution · 2024Article
- mBAT-combo: A more powerful test to detect gene-trait associations from GWAS data.American journal of human genetics · 2023Article
- Genetic heterogeneity: Challenges, impacts, and methods through an associative lens.Genetic epidemiology · 2022Review
- Connecting tree-ring phenotypes, genetic associations and transcriptomics to decipher the genomic architecture of drought adaptation in a widespread conifer.Molecular ecology · 2021Article
- Single-marker and haplotype-based genome-wide association studies for the number of teats in two heavy pig breeds.Animal genetics · 2021Article
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- A framework for integrating directed and undirected annotations to build explanatory models of cis-eQTL data.PLoS computational biology · 2020Article
- Atrial Fibrillation Genetics Update: Toward Clinical Implementation.Frontiers in cardiovascular medicine · 2019Review
- Genetic Predisposition, Clinical Risk Factor Burden, and Lifetime Risk of Atrial Fibrillation.Circulation · 2018Article
- Genetic basis of human congenital anomalies of the kidney and urinary tract.The Journal of clinical investigation · 2018Review
- Analysis of the joint effect of SNPs to identify independent loci and allelic heterogeneity in schizophrenia GWAS data.Translational psychiatry · 2017Article
- Detecting genetic association through shortest paths in a bidirected graph.Genetic epidemiology · 2017Article
- Article
- Genetic Risk Prediction of Atrial Fibrillation.Circulation · 2017Article
- BAYESIAN LARGE-SCALE MULTIPLE REGRESSION WITH SUMMARY STATISTICS FROM GENOME-WIDE ASSOCIATION STUDIES.The annals of applied statistics · 2017Article
- A method to estimate the contribution of regional genetic associations to complex traits from summary association statistics.Scientific reports · 2016Article
- JEPEGMIX: gene-level joint analysis of functional SNPs in cosmopolitan cohorts.Bioinformatics (Oxford, England) · 2016Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
There are many known examples of multiple semi-independent associations at individual loci; such associations might arise either because of true allelic heterogeneity or because of imperfect tagging of an unobserved causal variant. This phenomenon is of great importance in monogenic traits but has not yet been systematically investigated and quantified in complex-trait genome-wide association studies (GWASs). Here, we describe a multi-SNP association method that estimates the effect of loci harboring multiple association signals by using GWAS summary statistics. Applying the method to a large anthropometric GWAS meta-analysis (from the Genetic Investigation of Anthropometric Traits consortium study), we show that for height, body mass index (BMI), and waist-to-hip ratio (WHR), 3%, 2%, and 1%, respectively, of additional phenotypic variance can be explained on top of the previously reported 10% (height), 1.5% (BMI), and 1% (WHR). The method also permitted a substantial increase (by up to 50%) in the number of loci that replicate in a discovery-validation design. Specifically, we identified 74 loci at which the multi-SNP, a linear combination of SNPs, explains significantly more variance than does the best individual SNP. A detailed analysis of multi-SNPs shows that most of the additional variability explained is derived from SNPs that are not in linkage disequilibrium with the lead SNP, suggesting a major contribution of allelic heterogeneity to the missing heritability.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.