Within-sibship genome-wide association analyses decrease bias in estimates of direct genetic effects.
Within-sibship genome-wide association analyses decrease bias in estimates of direct genetic effects.
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DOI：
10.1038/s41588-022-01062-7
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发表时间：
2022-05
期刊：
影响因子：
30.8
通讯作者：
Davies, Neil M.
中科院分区：
文献类型：
--
作者：
Howe, Laurence J.;Nivard, Michel G.;Morris, Tim T.;Hansen, Ailin F.;Rasheed, Humaira;Cho, Yoonsu;Chittoor, Geetha;Ahlskog, Rafael;Lind, Penelope A.;Palviainen, Teemu;van der Zee, Matthijs D.;Cheesman, Rosa;Mangino, Massimo;Wang, Yunzhang;Li, Shuai;Klaric, Lucija;Ratliff, Scott M.;Bielak, Lawrence F.;Nygaard, Marianne;Giannelis, Alexandros;Willoughby, Emily A.;Reynolds, Chandra A.;Balbona, Jared V.;Andreassen, Ole A.;Ask, Helga;Baras, Aris;Bauer, Christopher R.;Boomsma, Dorret I.;Campbell, Archie;Campbell, Harry;Chen, Zhengming;Christofidou, Paraskevi;Corfield, Elizabeth;Dahm, Christina C.;Dokuru, Deepika R.;Evans, Luke M.;de Geus, Eco J. C.;Giddaluru, Sudheer;Gordon, Scott D.;Harden, K. Paige;Hill, W. David;Hughes, Amanda;Kerr, Shona M.;Kim, Yongkang;Kweon, Hyeokmoon;Latvala, Antti;Lawlor, Deborah A.;Li, Liming;Lin, Kuang;Magnus, Per;Magnusson, Patrik K. E.;Mallard, Travis T.;Martikainen, Pekka;Mills, Melinda C.;Njolstad, Pal Rasmus;Overton, John D.;Pedersen, Nancy L.;Porteous, David J.;Reid, Jeffrey;Silventoinen, Karri;Southey, Melissa C.;Stoltenberg, Camilla;Tucker-Drob, Elliot M.;Wright, Margaret J.;Kweon, Hyeokmoon;Hewitt, John K.;Keller, Matthew C.;Stallings, Michael C.;Lee, James J.;Christensen, Kaare;Kardia, Sharon L. R.;Peyser, Patricia A.;Smith, Jennifer A.;Wilson, James F.;Hopper, John L.;Hagg, Sara;Spector, Tim D.;Pingault, Jean-Baptiste;Plomin, Robert;Havdahl, Alexandra;Bartels, Meike;Martin, Nicholas G.;Oskarsson, Sven;Justice, Anne E.;Millwood, Iona Y.;Hveem, Kristian;Naess, Oyvind;Willer, Cristen J.;Asvold, Bjorn Olav;Koellinger, Philipp D.;Kaprio, Jaakko;Medland, Sarah E.;Walters, Robin G.;Benjamin, Daniel J.;Turley, Patrick;Evans, David M.;Smith, George Davey;Hayward, Caroline;Brumpton, Ben;Hemani, Gibran;Davies, Neil M.
来自无关个体的全基因组关联研究（GWAS）的估计捕获了遗传变异（直接效应），人口统计学（群体分层，重复交配）和亲属（间接遗传效应）的影响。基于家庭的GWAS设计可以控制人口统计学和间接遗传效应，但缺乏大规模的家庭数据集。我们结合了来自19个队列的178，086名兄弟姐妹的数据，以生成25种表型的群体（家庭间）和兄弟姐妹（家庭内）GWAS估计值。在身高、教育程度、首次生育年龄、子女数量、认知能力、抑郁症状和吸烟方面，兄弟姐妹内GWAS的估计值小于人口估计值。在下游SNP遗传力、遗传相关和孟德尔随机化分析中观察到一些差异。例如，受教育程度和身体质量指数之间的同胞遗传相关性逐渐减弱为零。相反，大多数分子表型（例如，低密度脂蛋白胆固醇）的分析通常是一致的。我们还发现了同胞内的证据，多基因适应较高的高度。在这里，我们说明了基于家庭的GWAS数据受人口统计学和间接遗传效应影响的表型的重要性。使用来自178，076名兄弟姐妹的数据进行的同胞内全基因组关联分析说明了基于人口和同胞内GWAS估计受人口统计学和间接遗传效应影响的表型之间的差异。
Estimates from genome-wide association studies (GWAS) of unrelated individuals capture effects of inherited variation (direct effects), demography (population stratification, assortative mating) and relatives (indirect genetic effects). Family-based GWAS designs can control for demographic and indirect genetic effects, but large-scale family datasets have been lacking. We combined data from 178,086 siblings from 19 cohorts to generate population (between-family) and within-sibship (within-family) GWAS estimates for 25 phenotypes. Within-sibship GWAS estimates were smaller than population estimates for height, educational attainment, age at first birth, number of children, cognitive ability, depressive symptoms and smoking. Some differences were observed in downstream SNP heritability, genetic correlations and Mendelian randomization analyses. For example, the within-sibship genetic correlation between educational attainment and body mass index attenuated towards zero. In contrast, analyses of most molecular phenotypes (for example, low-density lipoprotein-cholesterol) were generally consistent. We also found within-sibship evidence of polygenic adaptation on taller height. Here, we illustrate the importance of family-based GWAS data for phenotypes influenced by demographic and indirect genetic effects. Within-sibship genome-wide association analyses using data from 178,076 siblings illustrate differences between population-based and within-sibship GWAS estimates for phenotypes influenced by demographic and indirect genetic effects.
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影响因子：
4.5
作者：
Hwang LD;Tubbs JD;Luong J;Lundberg M;Moen GH;Wang G;Warrington NM;Sham PC;Cuellar-Partida G;Evans DM
通讯作者：
Evans DM
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
基因发现和多基因预测，从基因组全基因组协会的教育程度研究中，有110万个人。
影响因子：
30.8
作者：
Lee JJ;Wedow R;Okbay A;Kong E;Maghzian O;Zacher M;Nguyen-Viet TA;Bowers P;Sidorenko J;Karlsson Linnér R;Fontana MA;Kundu T;Lee C;Li H;Li R;Royer R;Timshel PN;Walters RK;Willoughby EA;Yengo L;23andMe Research Team;COGENT (Cognitive Genomics Consortium);Social Science Genetic Association Consortium;Alver M;Bao Y;Clark DW;Day FR;Furlotte NA;Joshi PK;Kemper KE;Kleinman A;Langenberg C;Mägi R;Trampush JW;Verma SS;Wu Y;Lam M;Zhao JH;Zheng Z;Boardman JD;Campbell H;Freese J;Harris KM;Hayward C;Herd P;Kumari M;Lencz T;Luan J;Malhotra AK;Metspalu A;Milani L;Ong KK;Perry JRB;Porteous DJ;Ritchie MD;Smart MC;Smith BH;Tung JY;Wareham NJ;Wilson JF;Beauchamp JP;Conley DC;Esko T;Lehrer SF;Magnusson PKE;Oskarsson S;Pers TH;Robinson MR;Thom K;Watson C;Chabris CF;Meyer MN;Laibson DI;Yang J;Johannesson M;Koellinger PD;Turley P;Visscher PM;Benjamin DJ;Cesarini D
通讯作者：
Cesarini D
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.
影响因子：
9.8
作者：
Abecasis, GR;Cardon, LR;Cookson, WOC
通讯作者：
Cookson, WOC