LD Score regression distinguishes confounding from polygenicity in genome-wide association studies.

LD Score regression distinguishes confounding from polygenicity in genome-wide association studies.
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DOI:
10.1038/ng.3211
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发表时间:
2015-03
期刊:
影响因子:
30.8
通讯作者:
Neale, Benjamin M.
Neale, Benjamin M.
中科院分区:
生物学1区
文献类型:
--
作者:
Bulik-Sullivan, Brendan K.;Loh, Po-Ru;Finucane, Hilary K.;Ripke, Stephan;Yang, Jian;Patterson, Nick;Daly, Mark J.;Price, Alkes L.;Neale, Benjamin M.

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多基因性(即,许多小的遗传效应)和混杂偏倚,如隐性相关性和群体分层,可以产生全基因组关联研究(GWAS)中检验统计量的膨胀分布。然而,目前的方法不能区分膨胀与真正的多基因信号和偏差。我们已经开发了一种方法,LD得分回归,量化的贡献,每个检验统计量和连锁不平衡(LD)之间的关系。LD评分回归截距可用于估计比基因组对照更强大和更准确的校正因子。我们发现强有力的证据表明,在许多大样本量的GWAS中,多基因性占大多数的检验统计膨胀。
Both polygenicity (i.e., many small genetic effects) and confounding biases, such as cryptic relatedness and population stratification, can yield an inflated distribution of test statistics in genome-wide association studies (GWAS). However, current methods cannot distinguish between inflation from true polygenic signal and bias. We have developed an approach, LD Score regression, that quantifies the contribution of each by examining the relationship between test statistics and linkage disequilibrium (LD). The LD Score regression intercept can be used to estimate a more powerful and accurate correction factor than genomic control. We find strong evidence that polygenicity accounts for the majority of test statistic inflation in many GWAS of large sample size.
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