Estimating genetic nurture with summary statistics of multigenerational genome-wide association studies

被引:32
作者
Wu, Yuchang [1 ,2 ]
Zhong, Xiaoyuan [1 ]
Lin, Yunong [1 ,3 ]
Zhao, Zijie [1 ]
Chen, Jiawen [3 ,4 ]
Zheng, Boyan [2 ,5 ]
Li, James J. [2 ,6 ,7 ]
Fletcher, Jason M. [2 ,5 ,8 ]
Lu, Qiongshi [1 ,2 ,3 ]
机构
[1] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI 53706 USA
[2] Univ Wisconsin, Ctr Demog Hlth & Aging, Madison, WI 53706 USA
[3] Univ Wisconsin, Dept Stat, Madison, WI 53706 USA
[4] Univ N Carolina, Dept Stat, Chapel Hill, NC 27514 USA
[5] Univ Wisconsin, Dept Sociol, Madison, WI 53706 USA
[6] Univ Wisconsin, Dept Psychol, Madison, WI 53706 USA
[7] Univ Wisconsin, Waisman Ctr, Madison, WI 53706 USA
[8] Univ Wisconsin, La Follette Sch Publ Affairs, Madison, WI 53706 USA
关键词
genetic nurture; indirect genetic effect; family-based study; GWAS; summary statistics; HUMAN-DISEASES; RISK; SPECTRUM; LOCI;
D O I
10.1073/pnas.2023184118
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Marginal effect estimates in genome-wide association studies (GWAS) are mixtures of direct and indirect genetic effects. Existing methods to dissect these effects require family-based, individuallevel genetic, and phenotypic data with large samples, which is difficult to obtain in practice. Here, we propose a statistical framework to estimate direct and indirect genetic effects using summary statistics from GWAS conducted on own and offspring phenotypes. Applied to birth weight, our method showed nearly identical results with those obtained using individual-level data. We also decomposed direct and indirect genetic effects of educational attainment (EA), which showed distinct patterns of genetic correlations with 45 complex traits. The known genetic correlations between EA and higher height, lower body mass index, lessactive smoking behavior, and better health outcomes were mostly explained by the indirect genetic component of EA. In contrast, the consistently identified genetic correlation of autism spectrum disorder (ASD) with higher EA resides in the direct genetic component. A polygenic transmission disequilibrium test showed a significant overtransmission of the direct component of EA from healthy parents to ASD probands. Taken together, we demonstrate that traditional GWAS approaches, in conjunction with offspring phenotypic data collection in existing cohorts, could greatly benefit studies on genetic nurture and shed important light on the interpretation of genetic associations for human complex traits.
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页数:10
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