A multi-ethnic epigenome-wide association study of leukocyte DNA methylation and blood lipids
Min-A Jhun, Michael Mendelson, Rory Wilson, Rahul Gondalia, Roby Joehanes, Elias Salfati, Xiaoping Zhao, Kim V.E. Braun, Anh Nguyet, Åsa K. Hedman, Tao Zhang, Elena Carnero‐Montoro, Jincheng Shen, Traci M. Bartz, Jennifer A. Brody, May E. Montasser, Jeff O’Connell, Chen Yao, Rui Xia, Eric Boerwinkle, Megan L. 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 B. J. van Meurs, André G. Uitterlinden, M. 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 Absher, Steve Horvath, Philip S. Tsao, Sharon L.R. Kardia, Bruce M. Psaty, Nona Sotoodehnia, Jordana T. Bell, Erik Ingelsson, Wei Chen, Abbas Dehghan, Donna K. Arnett, Mélanie Waldenberger, Lifang Hou, Eric A. Whitsel, Andrea Baccarelli, Daniel Levy, Myriam Fornage, Marguerite R. Irvin, Themistocles L. Assimes
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.