A more accurate method for colocalisation analysis allowing for multiple causal variants

被引:182
作者
Wallace, Chris [1 ,2 ]
机构
[1] Univ Cambridge, Cambridge Inst Therapeut Immunol & Infect Dis, Cambridge, England
[2] Univ Cambridge, MRC Biostat Unit, Cambridge, England
来源
PLOS GENETICS | 2021年 / 17卷 / 09期
基金
英国惠康基金;
关键词
REGRESSION; STATISTICS; SELECTION; SIGNALS; GWAS;
D O I
10.1371/journal.pgen.1009440
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
In genome-wide association studies (GWAS) it is now common to search for, and find, multiple causal variants located in close proximity. It has also become standard to ask whether different traits share the same causal variants, but one of the popular methods to answer this question, coloc, makes the simplifying assumption that only a single causal variant exists for any given trait in any genomic region. Here, we examine the potential of the recently proposed Sum of Single Effects (SuSiE) regression framework, which can be used for fine-mapping genetic signals, for use with coloc. SuSiE is a novel approach that allows evidence for association at multiple causal variants to be evaluated simultaneously, whilst separating the statistical support for each variant conditional on the causal signal being considered. We show this results in more accurate coloc inference than other proposals to adapt coloc for multiple causal variants based on conditioning. We therefore recommend that coloc be used in combination with SuSiE to optimise accuracy of colocalisation analyses when multiple causal variants exist.
引用
收藏
页数:11
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