基于汇总关联数据对比30种复杂性状的遗传结构

Contrasting the Genetic Architecture of 30 Complex Traits from Summary Association Data.

作者信息

Shi Huwenbo, Kichaev Gleb, Pasaniuc Bogdan

机构信息

Bioinformatics Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA 90024, USA.

Bioinformatics Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA 90024, USA; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90024, USA; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90024, USA.

出版信息

Am J Hum Genet. 2016 Jul 7;99(1):139-53. doi: 10.1016/j.ajhg.2016.05.013. Epub 2016 Jun 23.

Abstract

Variance-component methods that estimate the aggregate contribution of large sets of variants to the heritability of complex traits have yielded important insights into the genetic architecture of common diseases. Here, we introduce methods that estimate the total trait variance explained by the typed variants at a single locus in the genome (local SNP heritability) from genome-wide association study (GWAS) summary data while accounting for linkage disequilibrium among variants. We applied our estimator to ultra-large-scale GWAS summary data of 30 common traits and diseases to gain insights into their local genetic architecture. First, we found that common SNPs have a high contribution to the heritability of all studied traits. Second, we identified traits for which the majority of the SNP heritability can be confined to a small percentage of the genome. Third, we identified GWAS risk loci where the entire locus explains significantly more variance in the trait than the GWAS reported variants. Finally, we identified loci that explain a significant amount of heritability across multiple traits.

摘要

估计大量变异集对复杂性状遗传力的总体贡献的方差成分方法,已为常见疾病的遗传结构提供了重要见解。在此,我们介绍了一些方法,这些方法可从全基因组关联研究(GWAS)汇总数据中估计基因组中单个位点上分型变异所解释的总性状方差(局部SNP遗传力),同时考虑变异间的连锁不平衡。我们将我们的估计器应用于30种常见性状和疾病的超大规模GWAS汇总数据,以深入了解其局部遗传结构。首先,我们发现常见SNP对所有研究性状的遗传力有很高贡献。其次,我们确定了那些大部分SNP遗传力可局限于基因组一小部分的性状。第三,我们确定了全基因组关联研究风险位点,其中整个位点所解释的性状方差比全基因组关联研究报告的变异显著更多。最后,我们确定了在多个性状上解释大量遗传力的位点。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索