A global overview of pleiotropy and genetic architecture in complex traits

被引：759

作者：

Watanabe, Kyoko ^{[1
]}

Stringer, Sven ^{[1
]}

Frei, Oleksandr ^{[2
]}

Mirkov, Masa Umicevic ^{[1
]}

de Leeuw, Christiaan ^{[1
]}

Polderman, Tinca J. C. ^{[1
]}

van der Sluis, Sophie ^{[1
,3
]}

Andreassen, Ole A. ^{[2
,4
]}

Neale, Benjamin M. ^{[5
,6
,7
]}

Posthuma, Danielle ^{[1
,3
]}

机构：

[1] Vrije Univ Amsterdam, Dept Complex Trait Genet, Ctr Neurogen & Cognit Res, Neurosci Campus Amsterdam, Amsterdam, Netherlands

[2] Univ Oslo, KG Jebsen Ctr Psychosis Res, Inst Clin Med, NORMENT, Oslo, Norway

[3] Vrije Univ Amsterdam Med Ctr, Dept Clin Genet, Sect Complex Trait Genet, Neurosci Campus Amsterdam, Amsterdam, Netherlands

[4] Oslo Univ Hosp, Div Mental Hlth & Addict, Oslo, Norway

[5] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA

[6] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA

[7] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA

来源：

NATURE GENETICS | 2019年 / 51卷 / 09期

关键词：

LD SCORE REGRESSION; SNP HERITABILITY; GWAS; ASSOCIATION; RESOURCE; DATABASE; DISEASE;

D O I：

10.1038/s41588-019-0481-0

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

After a decade of genome-wide association studies (GWASs), fundamental questions in human genetics, such as the extent of pleiotropy across the genome and variation in genetic architecture across traits, are still unanswered. The current availability of hundreds of GWASs provides a unique opportunity to address these questions. We systematically analyzed 4,155 publicly available GWASs. For a subset of well-powered GWASs on 558 traits, we provide an extensive overview of pleiotropy and genetic architecture. We show that trait-associated loci cover more than half of the genome, and 90% of these overlap with loci from multiple traits. We find that potential causal variants are enriched in coding and flanking regions, as well as in regulatory elements, and show variation in polygenicity and discoverability of traits. Our results provide insights into how genetic variation contributes to trait variation. All GWAS results can be queried and visualized at the GWAS ATLAS resource (https://atlas.ctglab.nl).

引用

页码：1339 / +

页数：13

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