Causal effects on complex traits are similar for common variants across segments of different continental ancestries within admixed individuals

被引：54

作者：

Hou, Kangcheng ^{[1
]}

Ding, Yi ^{[1
]}

Xu, Ziqi ^{[2
]}

Wu, Yue ^{[2
]}

Bhattacharya, Arjun ^{[3
]}

Mester, Rachel ^{[4
]}

Belbin, Gillian M. ^{[5
,6
]}

Buyske, Steve ^{[7
]}

Conti, David V. ^{[8
]}

Darst, Burcu F. ^{[9
]}

Fornage, Myriam ^{[10
]}

Gignoux, Chris ^{[11
]}

Guo, Xiuqing ^{[12
]}

Haiman, Christopher ^{[8
]}

Kenny, Eimear E. ^{[5
,13
,14
]}

Kim, Michelle ^{[9
]}

Kooperberg, Charles ^{[9
]}

Lange, Leslie ^{[15
]}

Manichaikul, Ani ^{[16
]}

North, Kari E. ^{[7
,17
]}

Peters, Ulrike ^{[9
]}

Rasmussen-Torvik, Laura J. ^{[18
]}

Rich, Stephen S. ^{[16
]}

Rotter, Jerome I. ^{[12
]}

Wheeler, Heather E. ^{[19
,20
]}

Wojcik, Genevieve L. ^{[21
]}

Zhou, Ying ^{[9
]}

Sankararaman, Sriram ^{[1
,2
,22
,23
]}

Pasaniuc, Bogdan ^{[1
,3
,22
,23
]}

机构：

[1] Bioinformat Interdept Program, UCLA, Los Angeles, CA USA

[2] Dept Comp Sci, UCLA, Los Angeles, CA USA

[3] David Geffen Sch Med UCLA, Dept Pathol, Lab Med, Los Angeles, CA USA

[4] David Geffen Sch Med UCLA, Grad Program Biomath, Los Angeles, CA USA

[5] Inst Genom Hlth, Icahn Sch Med Mt Sinai, New York, NY USA

[6] Charles Bronfman Inst Personalized Med, Icahn Sch Med Mt Sinai, New York, NY USA

[7] Rutgers State Univ, Dept Stat, Piscataway, NJ USA

[8] Univ Southern Calif, Ctr Genet Epidemiol, Keck Sch Med, Los Angeles, CA USA

[9] Fred Hutchinson Canc Ctr, Div Publ Hlth Sci, Seattle, WA USA

[10] Univ Texas Hlth Sci Ctr, Brown Fdn Inst Mol Med, Houston, TX USA

[11] Univ Colorado, Div Biomed Informat & Personalized Med, Denver, CO USA

[12] Inst Translat Genom & Populat Sci, Lundquist Inst Harbor, UCLA Med Ctr, Dept Pediat, Torrance, CA USA

[13] Icahn Sch Med Mt Sinai, Dept Med, New York, NY USA

[14] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY USA

[15] Univ Colorado, Dept Med, Aurora, CO USA

[16] Univ Virginia, Ctr Publ Hlth Genom, Dept Publ Hlth Sci, Charlottesville, VA USA

[17] Univ North Carolina Chapel Hill, Dept Epidemiol, Chapel Hill, NC USA

[18] Northwestern Univ Feinberg Sch Med, Dept Prevent Med, Chicago, IL USA

[19] Loyola Univ Chicago, Dept Biol, Chicago, IL USA

[20] Loyola Univ Chicago, Program Bioinformat, Chicago, IL USA

[21] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA

[22] David Geffen Sch Med UCLA, Dept Computat Med, Los Angeles, CA USA

[23] David Geffen Sch Med UCLA, Dept Human Genet, Los Angeles, CA USA

来源：

NATURE GENETICS | 2023年 / 55卷 / 04期

基金：

美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; HERITABILITY; HETEROGENEITY; ARCHITECTURE; COMPONENTS; DISEASES;

D O I：

10.1038/s41588-023-01338-6

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Individuals of admixed ancestries (for example, African Americans) inherit a mosaic of ancestry segments (local ancestry) originating from multiple continental ancestral populations. This offers the unique opportunity of investigating the similarity of genetic effects on traits across ancestries within the same population. Here we introduce an approach to estimate correlation of causal genetic effects (r(admix)) across local ancestries and analyze 38 complex traits in African-European admixed individuals (N = 53,001) to observe very high correlations (meta-analysis r(admix) = 0.95, 95% credible interval 0.93-0.97), much higher than correlation of causal effects across continental ancestries. We replicate our results using regression-based methods from marginal genome-wide association study summary statistics. We also report realistic scenarios where regression-based methods yield inflated heterogeneity-by-ancestry due to ancestry-specific tagging of causal effects, and/or polygenicity. Our results motivate genetic analyses that assume minimal heterogeneity in causal effects by ancestry, with implications for the inclusion of ancestry-diverse individuals in studies. This analysis of individuals of admixed genetic ancestries suggests that complex trait causal variant effect sizes are, by and large, similar across ancestries, and discusses the implications for the study of these and other diverse populations.

引用

页码：549 / +

页数：28

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