Heritability and genomics of gene expression in peripheral blood

Fred A. Wright; Patrick F. Sullivan; Andrew I. Brooks; Fei Zou; Wei Sun; Kai Xia; Vered Madar; Rick Jansen; Wonil Chung; Yi Hui Zhou; Abdel Abdellaoui; Sandra Batista; Casey Butler; Guanhua Chen; Ting Huei Chen; David D'Ambrosio; Paul Gallins; Min Jin Ha; Jouke Jan Hottenga; Shunping Huang; Mathijs Kattenberg; Jaspreet Kochar; Christel M. Middeldorp; Ani Qu; Andrey Shabalin; Jay Tischfield; Laura Todd; Jung Ying Tzeng; Gerard Van Grootheest; Jacqueline M. Vink; Qi Wang; Wei Wang; Weibo Wang; Gonneke Willemsen; Johannes H. Smit; Eco J. De Geus; Zhaoyu Yin; Brenda W.J.H. Penninx; Dorret I. Boomsma

doi:10.1038/ng.2951

Heritability and genomics of gene expression in peripheral blood

Fred A. Wright, Patrick F. Sullivan, Andrew I. Brooks, Fei Zou, Wei Sun, Kai Xia, Vered Madar, Rick Jansen, Wonil Chung, Yi Hui Zhou, Abdel Abdellaoui, Sandra Batista, Casey Butler, Guanhua Chen, Ting Huei Chen, David D'Ambrosio, Paul Gallins, Min Jin Ha, Jouke Jan Hottenga, Shunping HuangMathijs Kattenberg, Jaspreet Kochar, Christel M. Middeldorp, Ani Qu, Andrey Shabalin, Jay Tischfield, Laura Todd, Jung Ying Tzeng, Gerard Van Grootheest, Jacqueline M. Vink, Qi Wang, Wei Wang, Weibo Wang, Gonneke Willemsen, Johannes H. Smit, Eco J. De Geus, Zhaoyu Yin, Brenda W.J.H. Penninx, Dorret I. Boomsma

Department of Statistics

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

179 Citations (Scopus)

Abstract

We assessed gene expression profiles in 2,752 twins, using a classic twin design to quantify expression heritability and quantitative trait loci (eQTLs) in peripheral blood. The most highly heritable genes (â ̂1/4777) were grouped into distinct expression clusters, enriched in gene-poor regions, associated with specific gene function or ontology classes, and strongly associated with disease designation. The design enabled a comparison of twin-based heritability to estimates based on dizygotic identity-by-descent sharing and distant genetic relatedness. Consideration of sampling variation suggests that previous heritability estimates have been upwardly biased. Genotyping of 2,494 twins enabled powerful identification of eQTLs, which we further examined in a replication set of 1,895 unrelated subjects. A large number of non-redundant local eQTLs (6,756) met replication criteria, whereas a relatively small number of distant eQTLs (165) met quality control and replication standards. Our results provide a new resource toward understanding the genetic control of transcription.

Original language	English
Pages (from-to)	430-437
Number of pages	8
Journal	Nature Genetics
Volume	46
Issue number	5
DOIs	https://doi.org/10.1038/ng.2951
Publication status	Published - 2014 May

All Science Journal Classification (ASJC) codes

Genetics

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Wright, F. A., Sullivan, P. F., Brooks, A. I., Zou, F., Sun, W., Xia, K., Madar, V., Jansen, R., Chung, W., Zhou, Y. H., Abdellaoui, A., Batista, S., Butler, C., Chen, G., Chen, T. H., D'Ambrosio, D., Gallins, P., Ha, M. J., Hottenga, J. J., ... Boomsma, D. I. (2014). Heritability and genomics of gene expression in peripheral blood. Nature Genetics, 46(5), 430-437. https://doi.org/10.1038/ng.2951

Wright, Fred A. ; Sullivan, Patrick F. ; Brooks, Andrew I. ; Zou, Fei ; Sun, Wei ; Xia, Kai ; Madar, Vered ; Jansen, Rick ; Chung, Wonil ; Zhou, Yi Hui ; Abdellaoui, Abdel ; Batista, Sandra ; Butler, Casey ; Chen, Guanhua ; Chen, Ting Huei ; D'Ambrosio, David ; Gallins, Paul ; Ha, Min Jin ; Hottenga, Jouke Jan ; Huang, Shunping ; Kattenberg, Mathijs ; Kochar, Jaspreet ; Middeldorp, Christel M. ; Qu, Ani ; Shabalin, Andrey ; Tischfield, Jay ; Todd, Laura ; Tzeng, Jung Ying ; Van Grootheest, Gerard ; Vink, Jacqueline M. ; Wang, Qi ; Wang, Wei ; Wang, Weibo ; Willemsen, Gonneke ; Smit, Johannes H. ; De Geus, Eco J. ; Yin, Zhaoyu ; Penninx, Brenda W.J.H. ; Boomsma, Dorret I. / Heritability and genomics of gene expression in peripheral blood. In: Nature Genetics. 2014 ; Vol. 46, No. 5. pp. 430-437.

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abstract = "We assessed gene expression profiles in 2,752 twins, using a classic twin design to quantify expression heritability and quantitative trait loci (eQTLs) in peripheral blood. The most highly heritable genes ({\^a}{\^ }1/4777) were grouped into distinct expression clusters, enriched in gene-poor regions, associated with specific gene function or ontology classes, and strongly associated with disease designation. The design enabled a comparison of twin-based heritability to estimates based on dizygotic identity-by-descent sharing and distant genetic relatedness. Consideration of sampling variation suggests that previous heritability estimates have been upwardly biased. Genotyping of 2,494 twins enabled powerful identification of eQTLs, which we further examined in a replication set of 1,895 unrelated subjects. A large number of non-redundant local eQTLs (6,756) met replication criteria, whereas a relatively small number of distant eQTLs (165) met quality control and replication standards. Our results provide a new resource toward understanding the genetic control of transcription.",

author = "Wright, {Fred A.} and Sullivan, {Patrick F.} and Brooks, {Andrew I.} and Fei Zou and Wei Sun and Kai Xia and Vered Madar and Rick Jansen and Wonil Chung and Zhou, {Yi Hui} and Abdel Abdellaoui and Sandra Batista and Casey Butler and Guanhua Chen and Chen, {Ting Huei} and David D'Ambrosio and Paul Gallins and Ha, {Min Jin} and Hottenga, {Jouke Jan} and Shunping Huang and Mathijs Kattenberg and Jaspreet Kochar and Middeldorp, {Christel M.} and Ani Qu and Andrey Shabalin and Jay Tischfield and Laura Todd and Tzeng, {Jung Ying} and {Van Grootheest}, Gerard and Vink, {Jacqueline M.} and Qi Wang and Wei Wang and Weibo Wang and Gonneke Willemsen and Smit, {Johannes H.} and {De Geus}, {Eco J.} and Zhaoyu Yin and Penninx, {Brenda W.J.H.} and Boomsma, {Dorret I.}",

year = "2014",

month = may,

doi = "10.1038/ng.2951",

language = "English",

volume = "46",

pages = "430--437",

journal = "Nature Genetics",

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Wright, FA, Sullivan, PF, Brooks, AI, Zou, F, Sun, W, Xia, K, Madar, V, Jansen, R, Chung, W, Zhou, YH, Abdellaoui, A, Batista, S, Butler, C, Chen, G, Chen, TH, D'Ambrosio, D, Gallins, P, Ha, MJ, Hottenga, JJ, Huang, S, Kattenberg, M, Kochar, J, Middeldorp, CM, Qu, A, Shabalin, A, Tischfield, J, Todd, L, Tzeng, JY, Van Grootheest, G, Vink, JM, Wang, Q, Wang, W, Wang, W, Willemsen, G, Smit, JH, De Geus, EJ, Yin, Z, Penninx, BWJH & Boomsma, DI 2014, 'Heritability and genomics of gene expression in peripheral blood', Nature Genetics, vol. 46, no. 5, pp. 430-437. https://doi.org/10.1038/ng.2951

Heritability and genomics of gene expression in peripheral blood. / Wright, Fred A.; Sullivan, Patrick F.; Brooks, Andrew I.; Zou, Fei; Sun, Wei; Xia, Kai; Madar, Vered; Jansen, Rick; Chung, Wonil; Zhou, Yi Hui; Abdellaoui, Abdel; Batista, Sandra; Butler, Casey; Chen, Guanhua; Chen, Ting Huei; D'Ambrosio, David; Gallins, Paul; Ha, Min Jin; Hottenga, Jouke Jan; Huang, Shunping; Kattenberg, Mathijs; Kochar, Jaspreet; Middeldorp, Christel M.; Qu, Ani; Shabalin, Andrey; Tischfield, Jay; Todd, Laura; Tzeng, Jung Ying; Van Grootheest, Gerard; Vink, Jacqueline M.; Wang, Qi; Wang, Wei; Wang, Weibo; Willemsen, Gonneke; Smit, Johannes H.; De Geus, Eco J.; Yin, Zhaoyu; Penninx, Brenda W.J.H.; Boomsma, Dorret I.

In: Nature Genetics, Vol. 46, No. 5, 05.2014, p. 430-437.

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

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AU - Wright, Fred A.

AU - Sullivan, Patrick F.

AU - Brooks, Andrew I.

AU - Zou, Fei

AU - Sun, Wei

AU - Xia, Kai

AU - Madar, Vered

AU - Jansen, Rick

AU - Chung, Wonil

AU - Zhou, Yi Hui

AU - Abdellaoui, Abdel

AU - Batista, Sandra

AU - Butler, Casey

AU - Chen, Guanhua

AU - Chen, Ting Huei

AU - D'Ambrosio, David

AU - Gallins, Paul

AU - Ha, Min Jin

AU - Hottenga, Jouke Jan

AU - Huang, Shunping

AU - Kattenberg, Mathijs

AU - Kochar, Jaspreet

AU - Middeldorp, Christel M.

AU - Qu, Ani

AU - Shabalin, Andrey

AU - Tischfield, Jay

AU - Todd, Laura

AU - Tzeng, Jung Ying

AU - Van Grootheest, Gerard

AU - Vink, Jacqueline M.

AU - Wang, Qi

AU - Wang, Wei

AU - Wang, Weibo

AU - Willemsen, Gonneke

AU - Smit, Johannes H.

AU - De Geus, Eco J.

AU - Yin, Zhaoyu

AU - Penninx, Brenda W.J.H.

AU - Boomsma, Dorret I.

PY - 2014/5

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