Genome partitioning of genetic variation for complex traits using common SNPs

被引：667

作者：

Yang, Jian ^{[1
]}

Manolio, Teri A. ^{[2
]}

Pasquale, Louis R. ^{[3
]}

Boerwinkle, Eric ^{[4
,5
]}

Caporaso, Neil ^{[6
]}

Cunningham, Julie M. ^{[7
]}

de Andrade, Mariza ^{[8
]}

Feenstra, Bjarke ^{[9
]}

Feingold, Eleanor ^{[10
]}

Hayes, M. Geoffrey ^{[11
]}

Hill, William G. ^{[12
]}

Landi, Maria Teresa ^{[6
]}

Alonso, Alvaro ^{[13
]}

Lettre, Guillaume ^{[14
]}

Lin, Peng ^{[15
]}

Ling, Hua ^{[16
]}

Lowe, William

Mathias, Rasika A. ^{[17
]}

Melbye, Mads ^{[9
]}

Pugh, Elizabeth ^{[16
]}

Cornelis, Marilyn C. ^{[18
]}

Weir, Bruce S. ^{[19
]}

Goddard, Michael E. ^{[20
,21
]}

Visscher, Peter M. ^{[1
]}

机构：

[1] Queensland Inst Med Res, Queensland Stat Genet Lab, Brisbane, Qld 4006, Australia

[2] NHGRI, Off Populat Genom, Bethesda, MD 20892 USA

[3] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA

[4] Univ Texas Hlth Sci Ctr, Div Epidemiol, Houston, TX USA

[5] Univ Texas Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA

[6] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA

[7] Mayo Clin, Coll Med, Dept Lab Med & Pathol, Rochester, MN USA

[8] Mayo Clin, Div Biomed Stat & Informat, Rochester, MN USA

[9] Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark

[10] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA

[11] Northwestern Univ, Feinberg Sch Med, Div Endocrinol Metab & Mol Med, Chicago, IL 60611 USA

[12] Univ Edinburgh, Inst Evolutionary Biol, Edinburgh, Midlothian, Scotland

[13] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA

[14] Univ Montreal, Montreal Heart Inst, Montreal, PQ, Canada

[15] Washington Univ, Sch Med, Human & Stat Genet Program, St Louis, MO USA

[16] Johns Hopkins Univ, Sch Med, Ctr Inherited Dis Res, Baltimore, MD USA

[17] Johns Hopkins Univ, Sch Med, Dept Gen Internal Med, Baltimore, MD USA

[18] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA

[19] Univ Washington, Dept Biostat, Seattle, WA 98195 USA

[20] Univ Melbourne, Dept Food & Agr Syst, Melbourne, Vic 3010, Australia

[21] Dept Primary Ind, Biosci Res Div, Bundoora, Vic, Australia

来源：

NATURE GENETICS | 2011年 / 43卷 / 06期

基金：

美国国家卫生研究院; 澳大利亚研究理事会; 加拿大健康研究院; 英国医学研究理事会;

关键词：

VON-WILLEBRAND-FACTOR; BODY-MASS INDEX; WIDE ASSOCIATION; LARGE PROPORTION; AGING RESEARCH; FACTOR-VIII; HERITABILITY; LOCI; POPULATION; VARIANTS;

D O I：

10.1038/ng.823

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

We estimate and partition genetic variation for height, body mass index (BMI), von Willebrand factor and QT interval (QTi) using 586,898 SNPs genotyped on 11,586 unrelated individuals. We estimate that similar to 45%, similar to 17%, similar to 25% and similar to 21% of the variance in height, BMI, von Willebrand factor and QTi, respectively, can be explained by all autosomal SNPs and a further similar to 0.5-1% can be explained by X chromosome SNPs. We show that the variance explained by each chromosome is proportional to its length, and that SNPs in or near genes explain more variation than SNPs between genes. We propose a new approach to estimate variation due to cryptic relatedness and population stratification. Our results provide further evidence that a substantial proportion of heritability is captured by common SNPs, that height, BMI and QTi are highly polygenic traits, and that the additive variation explained by a part of the genome is approximately proportional to the total length of DNA contained within genes therein.

引用

页码：519 / U44

页数：9

共 43 条

[1] Hundreds of variants clustered in genomic loci and biological pathways affect human height [J].

Allen, Hana Lango ;

Estrada, Karol ;

Lettre, Guillaume ;

Berndt, Sonja I. ;

Weedon, Michael N. ;

Rivadeneira, Fernando ;

Willer, Cristen J. ;

Jackson, Anne U. ;

Vedantam, Sailaja ;

Raychaudhuri, Soumya ;

Ferreira, Teresa ;

Wood, Andrew R. ;

Weyant, Robert J. ;

Segre, Ayellet V. ;

Speliotes, Elizabeth K. ;

Wheeler, Eleanor ;

Soranzo, Nicole ;

Park, Ju-Hyun ;

Yang, Jian ;

Gudbjartsson, Daniel ;

Heard-Costa, Nancy L. ;

Randall, Joshua C. ;

Qi, Lu ;

Smith, Albert Vernon ;

Maegi, Reedik ;

Pastinen, Tomi ;

Liang, Liming ;

Heid, Iris M. ;

Luan, Jian'an ;

Thorleifsson, Gudmar ;

Winkler, Thomas W. ;

Goddard, Michael E. ;

Lo, Ken Sin ;

Palmer, Cameron ;

Workalemahu, Tsegaselassie ;

Aulchenko, Yurii S. ;

Johansson, Asa ;

Zillikens, M. Carola ;

Feitosa, Mary F. ;

Esko, Tonu ;

Johnson, Toby ;

Ketkar, Shamika ;

Kraft, Peter ;

Mangino, Massimo ;

Prokopenko, Inga ;

Absher, Devin ;

Albrecht, Eva ;

Ernst, Florian ;

Glazer, Nicole L. ;

Hayward, Caroline .

NATURE, 2010, 467 (7317) :832-838

[2] A map of human genome variation from population-scale sequencing [J].

Altshuler, David ;

Durbin, Richard M. ;

Abecasis, Goncalo R. ;

Bentley, David R. ;

Chakravarti, Aravinda ;

Clark, Andrew G. ;

Collins, Francis S. ;

De la Vega, Francisco M. ;

Donnelly, Peter ;

Egholm, Michael ;

Flicek, Paul ;

Gabriel, Stacey B. ;

Gibbs, Richard A. ;

Knoppers, Bartha M. ;

Lander, Eric S. ;

Lehrach, Hans ;

Mardis, Elaine R. ;

McVean, Gil A. ;

Nickerson, DebbieA. ;

Peltonen, Leena ;

Schafer, Alan J. ;

Sherry, Stephen T. ;

Wang, Jun ;

Wilson, Richard K. ;

Gibbs, Richard A. ;

Deiros, David ;

Metzker, Mike ;

Muzny, Donna ;

Reid, Jeff ;

Wheeler, David ;

Wang, Jun ;

Li, Jingxiang ;

Jian, Min ;

Li, Guoqing ;

Li, Ruiqiang ;

Liang, Huiqing ;

Tian, Geng ;

Wang, Bo ;

Wang, Jian ;

Wang, Wei ;

Yang, Huanming ;

Zhang, Xiuqing ;

Zheng, Huisong ;

Lander, Eric S. ;

Altshuler, David L. ;

Ambrogio, Lauren ;

Bloom, Toby ;

Cibulskis, Kristian ;

Fennell, Tim J. ;

Gabriel, Stacey B. .

NATURE, 2010, 467 (7319) :1061-1073

[3]

Bulmer MG, 1985, The mathematical theory of quantitative genetics

[4] The Nurses' Health Study: Lifestyle and health among women [J].

Colditz, GA ;

Hankinson, SE .

NATURE REVIEWS CANCER, 2005, 5 (05) :388-396

[5] The Gene, Environment Association Studies Consortium (GENEVA): Maximizing the Knowledge Obtained from GWAS by Collaboration Across Studies of Multiple Conditions [J].

Cornelis, Marilyn C. ;

Agrawal, Arpana ;

Cole, John W. ;

Hansel, Nadia N. ;

Barnes, Kathleen C. ;

Beaty, Terri H. ;

Bennett, Siiri N. ;

Bierut, Laura J. ;

Boerwinkle, Eric ;

Doheny, Kimberly F. ;

Feenstra, Bjarke ;

Feingold, Eleanor ;

Fornage, Myriam ;

Haiman, Christopher A. ;

Harris, Emily L. ;

Hayes, M. Geoffrey ;

Heit, John A. ;

Hu, Frank B. ;

Kang, Jae H. ;

Laurie, Cathy C. ;

Ling, Hua ;

Manolio, Teri A. ;

Marazita, Mary L. ;

Mathias, Rasika A. ;

Mirel, Daniel B. ;

Paschall, Justin ;

Pasquale, Louis R. ;

Pugh, Elizabeth W. ;

Rice, John P. ;

Udren, Jenna ;

van Dam, Rob M. ;

Wang, Xiaojing ;

Wiggs, Janey L. ;

Williams, Kayleen ;

Yu, Kai .

GENETIC EPIDEMIOLOGY, 2010, 34 (04) :364-372

[6] Heritability of QT interval:: How much is explained by genes for resting heart rate? [J].

Dalageorgou, Chrysoula ;

Ge, Dongliang ;

Jamshidi, Yalda ;

Nolte, Ilja M. ;

Riese, Harriette ;

Savelieva, Irina ;

Carter, Nicholas D. ;

Spector, Tim D. ;

Snieder, Harold .

JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, 2008, 19 (04) :386-391

[7] The genetics of haemostasis:: a twin study [J].

de Lange, M ;

Snieder, H ;

Ariëns, RAS ;

Spector, TD ;

Grant, PJ .

LANCET, 2001, 357 (9250) :101-105

[8] Rare Variants Create Synthetic Genome-Wide Associations [J].

Dickson, Samuel P. ;

Wang, Kai ;

Krantz, Ian ;

Hakonarson, Hakon ;

Goldstein, David B. .

PLOS BIOLOGY, 2010, 8 (01)

[9] Genetic architecture of a complex trait and its implications for fitness and genome-wide association studies [J].

Eyre-Walker, Adam .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 :1752-1756

[10] A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity [J].

Frayling, Timothy M. ;

Timpson, Nicholas J. ;

Weedon, Michael N. ;

Zeggini, Eleftheria ;

Freathy, Rachel M. ;

Lindgren, Cecilia M. ;

Perry, John R. B. ;

Elliott, Katherine S. ;

Lango, Hana ;

Rayner, Nigel W. ;

Shields, Beverley ;

Harries, Lorna W. ;

Barrett, Jeffrey C. ;

Ellard, Sian ;

Groves, Christopher J. ;

Knight, Bridget ;

Patch, Ann-Marie ;

Ness, Andrew R. ;

Ebrahim, Shah ;

Lawlor, Debbie A. ;

Ring, Susan M. ;

Ben-Shlomo, Yoav ;

Jarvelin, Marjo-Riitta ;

Sovio, Ulla ;

Bennett, Amanda J. ;

Melzer, David ;

Ferrucci, Luigi ;

Loos, Ruth J. F. ;

Barroso, Ines ;

Wareham, Nicholas J. ;

Karpe, Fredrik ;

Owen, Katharine R. ;

Cardon, Lon R. ;

Walker, Mark ;

Hitman, Graham A. ;

Palmer, Colin N. A. ;

Doney, Alex S. F. ;

Morris, Andrew D. ;

Smith, George Davey ;

Hattersley, Andrew T. ;

McCarthy, Mark I. .

SCIENCE, 2007, 316 (5826) :889-894

← 1 2 3 4 5 →