Enrichment analyses identify shared associations for 25 quantitative traits in over 600,000 individuals from seven diverse ancestries.
Enrichment analyses identify shared associations for 25 quantitative traits in over 600,000 individuals from seven diverse ancestries.
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DOI：
10.1016/j.ajhg.2022.03.005
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发表时间：
2022-05-05
影响因子：
9.8
通讯作者：
中科院分区：
文献类型：
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作者：
自2005年以来，全基因组关联(GWA)数据集在很大程度上偏向于对欧洲血统个体进行抽样，最近的研究表明，由于各种令人困惑的挑战，从自我认同的欧洲个体估计的GWA结果不能转移到非欧洲个体。在这里，我们证明了在多个基因组尺度上聚合SNP水平的关联统计数据的浓缩分析-从基因到基因组区域和途径-在GWA时代一直没有得到充分利用，并可以产生关于复杂性状结构的遗传基础的生物学上可解释的假说。我们举例说明了通过浓缩分析产生的稳健关联的例子，同时研究了来自英国生物库和日本生物库中七个不同的自我识别人类祖先的566,786个个体，以及来自PAGE联盟的44,348个混合个体，包括非洲裔美国人、西班牙裔和拉丁美洲人、夏威夷原住民和美国印第安人/阿拉斯加原住民。我们确定了1,000个基因水平的关联，这些关联在这25个性状的至少两个祖先队列中具有全基因组意义，以及在欧洲、东亚和夏威夷土著队列中与甘油三酯水平高度保守的途径关联。
Since 2005, genome-wide association (GWA) datasets have been largely biased toward sampling European ancestry individuals, and recent studies have shown that GWA results estimated from self-identified European individuals are not transferable to non-European individuals because of various confounding challenges. Here, we demonstrate that enrichment analyses that aggregate SNP-level association statistics at multiple genomic scales—from genes to genomic regions and pathways—have been underutilized in the GWA era and can generate biologically interpretable hypotheses regarding the genetic basis of complex trait architecture. We illustrate examples of the robust associations generated by enrichment analyses while studying 25 continuous traits assayed in 566,786 individuals from seven diverse self-identified human ancestries in the UK Biobank and the Biobank Japan as well as 44,348 admixed individuals from the PAGE consortium including cohorts of African American, Hispanic and Latin American, Native Hawaiian, and American Indian/Alaska Native individuals. We identify 1,000 gene-level associations that are genome-wide significant in at least two ancestry cohorts across these 25 traits as well as highly conserved pathway associations with triglyceride levels in European, East Asian, and Native Hawaiian cohorts.
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影响因子：
--
作者：
Das J;Yu H
通讯作者：
Yu H
影响因子：
64.8
作者：
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者：
Marchini J
DOI：
10.1073/pnas.0906182107
发表时间：
2010-01-26
影响因子：
11.1
作者：
Eyre-Walker, Adam
通讯作者：
Eyre-Walker, Adam
影响因子：
1.4
作者：
Edge, Michael D.;Rosenberg, Noah A.
通讯作者：
Rosenberg, Noah A.
影响因子：
30.8
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.
通讯作者：
Neale, Benjamin M.