A multi-ethnic epigenome-wide association study of leukocyte DNA methylation and blood lipids

Mina A. Jhun; Michael Mendelson; Rory Wilson; Rahul Gondalia; Roby Joehanes; Elias Salfati; Xiaoping Zhao; Kim Valeska Emilie Braun; Anh Nguyet Do; Åsa K. Hedman; Tao Zhang; Elena Carnero-Montoro; Jincheng Shen; Traci M. Bartz; Jennifer A. Brody; May E. Montasser; Jeff R. O’Connell; Chen Yao; Rui Xia; Eric Boerwinkle; Megan Grove; Weihua Guan; Pfeiffer Liliane; Paula Singmann; Martina Müller-Nurasyid; Thomas Meitinger; Christian Gieger; Annette Peters; Wei Zhao; Erin B. Ware; Jennifer A. Smith; Klodian Dhana; Joyce van Meurs; Andre Uitterlinden; Mohammad Arfan Ikram; Mohsen Ghanbari; Deugi Zhi; Stefan Gustafsson; Lars Lind; Shengxu Li; Dianjianyi Sun; Tim D. Spector; Yii der Ida Chen; Coleen Damcott; Alan R. Shuldiner; Devin M. Absher; Steve Horvath; Philip S. Tsao; Sharon Kardia; Bruce M. Psaty; Nona Sotoodehnia; Jordana T. Bell; Erik Ingelsson; Wei Chen; Abbas Dehghan; Donna K. Arnett; Melanie Waldenberger; Lifang Hou; Eric A. Whitsel; Andrea Baccarelli; Daniel Levy; Myriam Fornage; Marguerite R. Irvin; Themistocles L. Assimes

doi:10.1038/s41467-021-23899-y

A multi-ethnic epigenome-wide association study of leukocyte DNA methylation and blood lipids

Mina A. Jhun, Michael Mendelson, Rory Wilson, Rahul Gondalia, Roby Joehanes, Elias Salfati, Xiaoping Zhao, Kim Valeska Emilie Braun, Anh Nguyet Do, Åsa K. Hedman, Tao Zhang, Elena Carnero-Montoro, Jincheng Shen, Traci M. Bartz, Jennifer A. Brody, May E. Montasser, Jeff R. O’Connell, Chen Yao, Rui Xia, Eric BoerwinkleMegan Grove, Weihua Guan, Pfeiffer Liliane, Paula Singmann, Martina Müller-Nurasyid, Thomas Meitinger, Christian Gieger, Annette Peters, Wei Zhao, Erin B. Ware, Jennifer A. Smith, Klodian Dhana, Joyce van Meurs, Andre Uitterlinden, Mohammad Arfan Ikram, Mohsen Ghanbari, Deugi Zhi, Stefan Gustafsson, Lars Lind, Shengxu Li, Dianjianyi Sun, Tim D. Spector, Yii der Ida Chen, Coleen Damcott, Alan R. Shuldiner, Devin M. Absher, Steve Horvath, Philip S. Tsao, Sharon Kardia, Bruce M. Psaty, Nona Sotoodehnia, Jordana T. Bell, Erik Ingelsson, Wei Chen, Abbas Dehghan, Donna K. Arnett, Melanie Waldenberger, Lifang Hou, Eric A. Whitsel, Andrea Baccarelli, Daniel Levy, Myriam Fornage, Marguerite R. Irvin, Themistocles L. Assimes

Biostatistics

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Abstract

Here we examine the association between DNA methylation in circulating leukocytes and blood lipids in a multi-ethnic sample of 16,265 subjects. We identify 148, 35, and 4 novel associations among Europeans, African Americans, and Hispanics, respectively, and an additional 186 novel associations through a trans-ethnic meta-analysis. We observe a high concordance in the direction of effects across racial/ethnic groups, a high correlation of effect sizes between high-density lipoprotein and triglycerides, a modest overlap of associations with epigenome-wide association studies of other cardio-metabolic traits, and a largely non-overlap with lipid loci identified to date through genome-wide association studies. Thirty CpGs reached significance in at least 2 racial/ethnic groups including 7 that showed association with the expression of an annotated gene. CpGs annotated to CPT1A showed evidence of being influenced by triglycerides levels. DNA methylation levels of circulating leukocytes show robust and consistent association with blood lipid levels across multiple racial/ethnic groups.

Original language	English (US)
Article number	3987
Journal	Nature communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-021-23899-y
State	Published - Dec 1 2021

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Publisher Copyright:
© 2021, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.

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Jhun, M. A., Mendelson, M., Wilson, R., Gondalia, R., Joehanes, R., Salfati, E., Zhao, X., Braun, K. V. E., Do, A. N., Hedman, Å. K., Zhang, T., Carnero-Montoro, E., Shen, J., Bartz, T. M., Brody, J. A., Montasser, M. E., O’Connell, J. R., Yao, C., Xia, R., ... Assimes, T. L. (2021). A multi-ethnic epigenome-wide association study of leukocyte DNA methylation and blood lipids. Nature communications, 12(1), Article 3987. https://doi.org/10.1038/s41467-021-23899-y

Jhun, MA, Mendelson, M, Wilson, R, Gondalia, R, Joehanes, R, Salfati, E, Zhao, X, Braun, KVE, Do, AN, Hedman, ÅK, Zhang, T, Carnero-Montoro, E, Shen, J, Bartz, TM, Brody, JA, Montasser, ME, O’Connell, JR, Yao, C, Xia, R, Boerwinkle, E, Grove, M, Guan, W, Liliane, P, Singmann, P, Müller-Nurasyid, M, Meitinger, T, Gieger, C, Peters, A, Zhao, W, Ware, EB, Smith, JA, Dhana, K, van Meurs, J, Uitterlinden, A, Ikram, MA, Ghanbari, M, Zhi, D, Gustafsson, S, Lind, L, Li, S, Sun, D, Spector, TD, Chen, YDI, Damcott, C, Shuldiner, AR, Absher, DM, Horvath, S, Tsao, PS, Kardia, S, Psaty, BM, Sotoodehnia, N, Bell, JT, Ingelsson, E, Chen, W, Dehghan, A, Arnett, DK, Waldenberger, M, Hou, L, Whitsel, EA, Baccarelli, A, Levy, D, Fornage, M, Irvin, MR & Assimes, TL 2021, 'A multi-ethnic epigenome-wide association study of leukocyte DNA methylation and blood lipids', Nature communications, vol. 12, no. 1, 3987. https://doi.org/10.1038/s41467-021-23899-y

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abstract = "Here we examine the association between DNA methylation in circulating leukocytes and blood lipids in a multi-ethnic sample of 16,265 subjects. We identify 148, 35, and 4 novel associations among Europeans, African Americans, and Hispanics, respectively, and an additional 186 novel associations through a trans-ethnic meta-analysis. We observe a high concordance in the direction of effects across racial/ethnic groups, a high correlation of effect sizes between high-density lipoprotein and triglycerides, a modest overlap of associations with epigenome-wide association studies of other cardio-metabolic traits, and a largely non-overlap with lipid loci identified to date through genome-wide association studies. Thirty CpGs reached significance in at least 2 racial/ethnic groups including 7 that showed association with the expression of an annotated gene. CpGs annotated to CPT1A showed evidence of being influenced by triglycerides levels. DNA methylation levels of circulating leukocytes show robust and consistent association with blood lipid levels across multiple racial/ethnic groups.",

author = "Jhun, {Mina A.} and Michael Mendelson and Rory Wilson and Rahul Gondalia and Roby Joehanes and Elias Salfati and Xiaoping Zhao and Braun, {Kim Valeska Emilie} and Do, {Anh Nguyet} and Hedman, {{\AA}sa K.} and Tao Zhang and Elena Carnero-Montoro and Jincheng Shen and Bartz, {Traci M.} and Brody, {Jennifer A.} and Montasser, {May E.} and O{\textquoteright}Connell, {Jeff R.} and Chen Yao and Rui Xia and Eric Boerwinkle and Megan Grove and Weihua Guan and Pfeiffer Liliane and Paula Singmann and Martina M{\"u}ller-Nurasyid and Thomas Meitinger and Christian Gieger and Annette Peters and Wei Zhao and Ware, {Erin B.} and Smith, {Jennifer A.} and Klodian Dhana and {van Meurs}, Joyce and Andre Uitterlinden and Ikram, {Mohammad Arfan} and Mohsen Ghanbari and Deugi Zhi and Stefan Gustafsson and Lars Lind and Shengxu Li and Dianjianyi Sun and Spector, {Tim D.} and Chen, {Yii der Ida} and Coleen Damcott and Shuldiner, {Alan R.} and Absher, {Devin M.} and Steve Horvath and Tsao, {Philip S.} and Sharon Kardia and Psaty, {Bruce M.} and Nona Sotoodehnia and Bell, {Jordana T.} and Erik Ingelsson and Wei Chen and Abbas Dehghan and Arnett, {Donna K.} and Melanie Waldenberger and Lifang Hou and Whitsel, {Eric A.} and Andrea Baccarelli and Daniel Levy and Myriam Fornage and Irvin, {Marguerite R.} and Assimes, {Themistocles L.}",

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AU - Gondalia, Rahul

AU - Joehanes, Roby

AU - Salfati, Elias

AU - Zhao, Xiaoping

AU - Braun, Kim Valeska Emilie

AU - Do, Anh Nguyet

AU - Hedman, Åsa K.

AU - Zhang, Tao

AU - Carnero-Montoro, Elena

AU - Shen, Jincheng

AU - Bartz, Traci M.

AU - Brody, Jennifer A.

AU - Montasser, May E.

AU - O’Connell, Jeff R.

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AU - Xia, Rui

AU - Boerwinkle, Eric

AU - Grove, Megan

AU - Guan, Weihua

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AU - Singmann, Paula

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AU - Gieger, Christian

AU - Peters, Annette

AU - Zhao, Wei

AU - Ware, Erin B.

AU - Smith, Jennifer A.

AU - Dhana, Klodian

AU - van Meurs, Joyce

AU - Uitterlinden, Andre

AU - Ikram, Mohammad Arfan

AU - Ghanbari, Mohsen

AU - Zhi, Deugi

AU - Gustafsson, Stefan

AU - Lind, Lars

AU - Li, Shengxu

AU - Sun, Dianjianyi

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AU - Chen, Yii der Ida

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AU - Assimes, Themistocles L.

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A multi-ethnic epigenome-wide association study of leukocyte DNA methylation and blood lipids

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