Assessing the contribution of rare variants to complex trait heritability from whole-genome sequence data.
Assessing the contribution of rare variants to complex trait heritability from whole-genome sequence data.
复制标题
DOI：
10.1038/s41588-021-00997-7
复制
发表时间：
2022-03
期刊：
影响因子：
30.8
通讯作者：
Visscher, Peter M.
中科院分区：
文献类型：
--
作者：
Wainschtein, Pierrick;Jain, Deepti;Zheng, Zhili;Cupples, L. Adrienne;Shadyab, Aladdin H.;McKnight, Barbara;Shoemaker, Benjamin M.;Mitchell, Braxton D.;Psaty, Bruce M.;Kooperberg, Charles;Liu, Ching-Ti;Albert, Christine M.;Roden, Dan;Chasman, Daniel, I;Darbar, Dawood;Lloyd-Jones, Donald M.;Arnett, Donna K.;Regan, Elizabeth A.;Boerwinkle, Eric;Rotter, Jerome, I;O'Connell, Jeffrey R.;Yanek, Lisa R.;de Andrade, Mariza;Allison, Matthew A.;Mcdonald, Merry-Lynn N.;Chung, Mina K.;Fornage, Myriam;Chami, Nathalie;Smith, Nicholas L.;Ellinor, Patrick T.;Vasan, Ramachandran S.;Mathias, Rasika A.;Loos, Ruth J. F.;Rich, Stephen S.;Lubitz, Steven A.;Heckbert, Susan R.;Redline, Susan;Guo, Xiuqing;Chen, Y-D Ida;Laurie, Cecelia A.;Hernandez, Ryan D.;McGarvey, Stephen T.;Goddard, Michael E.;Laurie, Cathy C.;North, Kari E.;Lange, Leslie A.;Weir, Bruce S.;Yengo, Loic;Yang, Jian;Visscher, Peter M.
对无关个体的全基因组关联研究数据的分析表明，对于人类性状和疾病，大约三分之一到三分之二的遗传力被常见的SNP捕获。然而，尚不清楚剩余的遗传性是否是由于常见SNP对因果变异的不完善标记，特别是如果因果变异是罕见的。在这里，我们从25，465名欧洲血统无关个体的全基因组序列数据中估计了身高和体重指数（BMI）的遗传力。身高和BMI的估计遗传力分别为0.68（SE 0.10）和0.30（SE 0.10）。与相邻变体处于低连锁不平衡（LD）的低MAF变体富集遗传性，对于蛋白质改变变体在更大程度上富集遗传性，这与其上的阴性选择一致。我们的研究结果表明，罕见的变异，特别是那些在低LD地区，是一个主要来源的复杂性状和疾病的遗传力仍然缺失。
Analyses of data from genome-wide association studies on unrelated individuals have shown that for human traits and disease, approximately one-third to two-thirds of heritability is captured by common SNPs. However, it is not known whether the remaining heritability is due to the imperfect tagging of causal variants by common SNPs, in particular if the causal variants are rare. Here we estimated heritability for height and body mass index (BMI) from whole-genome sequence data on 25,465 unrelated individuals of European ancestry. The estimated heritability was 0.68 (SE 0.10) for height and 0.30 (SE 0.10) for BMI. Low-MAF variants in low linkage disequilibrium (LD) with neighbouring variants were enriched for heritability, to a greater extent for protein-altering variants, consistent with negative selection thereon. Our results imply that rare variants, in particular those in regions of low LD, are a major source of the still missing heritability of complex traits and disease.
登录
查看更多内容
DOI：
10.1002/ajhb.22917
发表时间：
2017-01
期刊：
American journal of human biology : the official journal of the Human Biology Council
影响因子：
--
作者：
Stulp G;Simons MJ;Grasman S;Pollet TV
通讯作者：
Pollet TV
影响因子：
9.8
作者：
Gusev, Alexander;Lee, S. Hong;Price, Alkes L.
通讯作者：
Price, Alkes L.
影响因子：
30.8
作者：
Finucane HK;Bulik-Sullivan B;Gusev A;Trynka G;Reshef Y;Loh PR;Anttila V;Xu H;Zang C;Farh K;Ripke S;Day FR;ReproGen Consortium;Schizophrenia Working Group of the Psychiatric Genomics Consortium;RACI Consortium;Purcell S;Stahl E;Lindstrom S;Perry JR;Okada Y;Raychaudhuri S;Daly MJ;Patterson N;Neale BM;Price AL
通讯作者：
Price AL
影响因子：
56.9
作者：
Nurk, Sergey;Koren, Sergey;Rhie, Arang;Rautiainen, Mikko;Bzikadze, Andrey V;Mikheenko, Alla;Vollger, Mitchell R;Altemose, Nicolas;Uralsky, Lev;Gershman, Ariel;Aganezov, Sergey;Hoyt, Savannah J;Diekhans, Mark;Logsdon, Glennis A;Alonge, Michael;Antonarakis, Stylianos E;Borchers, Matthew;Bouffard, Gerard G;Brooks, Shelise Y;Caldas, Gina V;Chen, Nae-Chyun;Cheng, Haoyu;Chin, Chen-Shan;Chow, William;de Lima, Leonardo G;Dishuck, Philip C;Durbin, Richard;Dvorkina, Tatiana;Fiddes, Ian T;Formenti, Giulio;Fulton, Robert S;Fungtammasan, Arkarachai;Garrison, Erik;Grady, Patrick G S;Graves-Lindsay, Tina A;Hall, Ira M;Hansen, Nancy F;Hartley, Gabrielle A;Haukness, Marina;Howe, Kerstin;Hunkapiller, Michael W;Jain, Chirag;Jain, Miten;Jarvis, Erich D;Kerpedjiev, Peter;Kirsche, Melanie;Kolmogorov, Mikhail;Korlach, Jonas;Kremitzki, Milinn;Li, Heng;Maduro, Valerie V;Marschall, Tobias;McCartney, Ann M;McDaniel, Jennifer;Miller, Danny E;Mullikin, James C;Myers, Eugene W;Olson, Nathan D;Paten, Benedict;Peluso, Paul;Pevzner, Pavel A;Porubsky, David;Potapova, Tamara;Rogaev, Evgeny I;Rosenfeld, Jeffrey A;Salzberg, Steven L;Schneider, Valerie A;Sedlazeck, Fritz J;Shafin, Kishwar;Shew, Colin J;Shumate, Alaina;Sims, Ying;Smit, Arian F A;Soto, Daniela C;Sovic, Ivan;Storer, Jessica M;Streets, Aaron;Sullivan, Beth A;Thibaud-Nissen, Francoise;Torrance, James;Wagner, Justin;Walenz, Brian P;Wenger, Aaron;Wood, Jonathan M D;Xiao, Chunlin;Yan, Stephanie M;Young, Alice C;Zarate, Samantha;Surti, Urvashi;McCoy, Rajiv C;Dennis, Megan Y;Alexandrov, Ivan A;Gerton, Jennifer L;O'Neill, Rachel J;Timp, Winston;Zook, Justin M;Schatz, Michael C;Eichler, Evan E;Miga, Karen H;Phillippy, Adam M
通讯作者：
Phillippy, Adam M
DOI：
10.1038/ejhg.2017.51
发表时间：
2017-06
期刊：
European journal of human genetics : EJHG
影响因子：
--
作者：
Mitt M;Kals M;Pärn K;Gabriel SB;Lander ES;Palotie A;Ripatti S;Morris AP;Metspalu A;Esko T;Mägi R;Palta P
通讯作者：
Palta P