Genome partitioning of genetic variation for complex traits using common SNPs

Jian Yang; Teri A. Manolio; Louis R. Pasquale; Eric Boerwinkle; Neil Caporaso; Julie M. Cunningham; Mariza De Andrade; Bjarke Feenstra; Eleanor Feingold; M. Geoffrey Hayes; William G. Hill; Maria Teresa Landi; Alvaro Alonso; Guillaume Lettre; Peng Lin; Hua Ling; William Lowe; Rasika A. Mathias; Mads Melbye; Elizabeth Pugh; Marilyn C. Cornelis; Bruce S. Weir; Michael E. Goddard; Peter M. Visscher

doi:10.1038/ng.823

Genome partitioning of genetic variation for complex traits using common SNPs

Jian Yang, Teri A. Manolio, Louis R. Pasquale, Eric Boerwinkle, Neil Caporaso, Julie M. Cunningham, Mariza De Andrade, Bjarke Feenstra, Eleanor Feingold, M. Geoffrey Hayes, William G. Hill, Maria Teresa Landi, Alvaro Alonso, Guillaume Lettre, Peng Lin, Hua Ling, William Lowe, Rasika A. Mathias, Mads Melbye, Elizabeth PughMarilyn C. Cornelis, Bruce S. Weir, Michael E. Goddard, Peter M. Visscher

Epidemiology

Research output: Contribution to journal › Article › peer-review

660 Scopus citations

Abstract

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 ̃45%, ̃17%, ̃25% and ̃21% of the variance in height, BMI, von Willebrand factor and QTi, respectively, can be explained by all autosomal SNPs and a further ̃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.

Original language	English (US)
Pages (from-to)	519-525
Number of pages	7
Journal	Nature Genetics
Volume	43
Issue number	6
DOIs	https://doi.org/10.1038/ng.823
State	Published - Jun 2011

Bibliographical note

Funding Information:
Funding support for the Gene, Environment Association Studies (GENEVA) project has been provided through the US National Institutes of Health Genes, Environment and Health Initiative. For the ARIC project, support was from U01 HG 004402 (PI: E.A. Boerwinkle). For the NHS and HPFS support is from U01 HG 004399 and U01 HG 004728 (PIs: F.B. Hu and L.R. Pasquale). The genotyping for the ARIC, NHS and HPFS studies was performed at the Broad Institute of MIT and Harvard with funding support from U01 HG04424 (PI: S. Gabriel). The GENEVA Coordinating Center receives support from U01 HG 004446 (PI: B.S. Weir). Assistance with GENEVA data cleaning was provided by the National Center for Biotechnology Information. D. Crosslin and C. Laurie of the GENEVA project assisted in making the data available for analysis. A Physician Scientist Award from Research to Prevent Blindness in New York City also supports L.R.P. M.C.C. is a recipient of a Canadian Institutes of Health Research Fellowship. We acknowledge funding from the Australian National Health and Medical Research Council (NHMRC grants 389892 and 613672) and the Australian Research Council (ARC grants DP0770096 and DP1093900). We thank D. Posthuma for discussions and the referees for constructive comments.

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Yang, J., Manolio, T. A., Pasquale, L. R., Boerwinkle, E., Caporaso, N., Cunningham, J. M., De Andrade, M., Feenstra, B., Feingold, E., Hayes, M. G., Hill, W. G., Landi, M. T., Alonso, A., Lettre, G., Lin, P., Ling, H., Lowe, W., Mathias, R. A., Melbye, M., ... Visscher, P. M. (2011). Genome partitioning of genetic variation for complex traits using common SNPs. Nature Genetics, 43(6), 519-525. https://doi.org/10.1038/ng.823

Yang, J, Manolio, TA, Pasquale, LR, Boerwinkle, E, Caporaso, N, Cunningham, JM, De Andrade, M, Feenstra, B, Feingold, E, Hayes, MG, Hill, WG, Landi, MT, Alonso, A, Lettre, G, Lin, P, Ling, H, Lowe, W, Mathias, RA, Melbye, M, Pugh, E, Cornelis, MC, Weir, BS, Goddard, ME & Visscher, PM 2011, 'Genome partitioning of genetic variation for complex traits using common SNPs', Nature Genetics, vol. 43, no. 6, pp. 519-525. https://doi.org/10.1038/ng.823

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title = "Genome partitioning of genetic variation for complex traits using common SNPs",

abstract = "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{\~ }45%,{\~ }17%,{\~ }25% and{\~ }21% of the variance in height, BMI, von Willebrand factor and QTi, respectively, can be explained by all autosomal SNPs and a further{\~ }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.",

author = "Jian Yang and Manolio, {Teri A.} and Pasquale, {Louis R.} and Eric Boerwinkle and Neil Caporaso and Cunningham, {Julie M.} and {De Andrade}, Mariza and Bjarke Feenstra and Eleanor Feingold and Hayes, {M. Geoffrey} and Hill, {William G.} and Landi, {Maria Teresa} and Alvaro Alonso and Guillaume Lettre and Peng Lin and Hua Ling and William Lowe and Mathias, {Rasika A.} and Mads Melbye and Elizabeth Pugh and Cornelis, {Marilyn C.} and Weir, {Bruce S.} and Goddard, {Michael E.} and Visscher, {Peter M.}",

note = "Funding Information: Funding support for the Gene, Environment Association Studies (GENEVA) project has been provided through the US National Institutes of Health Genes, Environment and Health Initiative. For the ARIC project, support was from U01 HG 004402 (PI: E.A. Boerwinkle). For the NHS and HPFS support is from U01 HG 004399 and U01 HG 004728 (PIs: F.B. Hu and L.R. Pasquale). The genotyping for the ARIC, NHS and HPFS studies was performed at the Broad Institute of MIT and Harvard with funding support from U01 HG04424 (PI: S. Gabriel). The GENEVA Coordinating Center receives support from U01 HG 004446 (PI: B.S. Weir). Assistance with GENEVA data cleaning was provided by the National Center for Biotechnology Information. D. Crosslin and C. Laurie of the GENEVA project assisted in making the data available for analysis. A Physician Scientist Award from Research to Prevent Blindness in New York City also supports L.R.P. M.C.C. is a recipient of a Canadian Institutes of Health Research Fellowship. We acknowledge funding from the Australian National Health and Medical Research Council (NHMRC grants 389892 and 613672) and the Australian Research Council (ARC grants DP0770096 and DP1093900). We thank D. Posthuma for discussions and the referees for constructive comments.",

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AU - Caporaso, Neil

AU - Cunningham, Julie M.

AU - De Andrade, Mariza

AU - Feenstra, Bjarke

AU - Feingold, Eleanor

AU - Hayes, M. Geoffrey

AU - Hill, William G.

AU - Landi, Maria Teresa

AU - Alonso, Alvaro

AU - Lettre, Guillaume

AU - Lin, Peng

AU - Ling, Hua

AU - Lowe, William

AU - Mathias, Rasika A.

AU - Melbye, Mads

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AU - Cornelis, Marilyn C.

AU - Weir, Bruce S.

AU - Goddard, Michael E.

AU - Visscher, Peter M.

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Genome partitioning of genetic variation for complex traits using common SNPs

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