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

• Published in: Nature communications Vol. 12; no. 1; pp. 3987 - 13
• Main Authors: Jhun, Min-A, Mendelson, Michael, Wilson, Rory, Gondalia, Rahul, Joehanes, Roby, Salfati, Elias, Zhao, Xiaoping, Braun, Kim Valeska Emilie, Do, Anh Nguyet, Hedman, Åsa K, Zhang, Tao, Carnero-Montoro, Elena, Shen, Jincheng, Bartz, Traci M, Brody, Jennifer A, Montasser, May E, O'Connell, Jeff R, Yao, Chen, Xia, Rui, Boerwinkle, Eric, Grove, Megan, Guan, Weihua, Liliane, Pfeiffer, Singmann, Paula, Müller-Nurasyid, Martina, Meitinger, Thomas, Gieger, Christian, Peters, Annette, Zhao, Wei, Ware, Erin B, Smith, Jennifer A, Dhana, Klodian, van Meurs, Joyce, Uitterlinden, Andre, Ikram, Mohammad Arfan, Ghanbari, Mohsen, Zhi, Deugi, Gustafsson, Stefan, Lind, Lars, Li, Shengxu, Sun, Dianjianyi, Spector, Tim D, Chen, Yii-der Ida, Damcott, Coleen, Shuldiner, Alan R, Absher, Devin M, Horvath, Steve, Tsao, Philip S, Kardia, Sharon, Psaty, Bruce M, Sotoodehnia, Nona, Bell, Jordana T, Ingelsson, Erik, Chen, Wei, Dehghan, Abbas, Arnett, Donna K, Waldenberger, Melanie, Hou, Lifang, Whitsel, Eric A, Baccarelli, Andrea, Levy, Daniel, Fornage, Myriam, Irvin, Marguerite R, Assimes, Themistocles L
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 28.06.2021; Nature Publishing Group UK; Nature Portfolio
• Subjects: Adult; Aged; Black or African American; Blood circulation; Blood levels; Cardiovascular diseases; Carnitine O-Palmitoyltransferase - genetics; CpG islands; CpG Islands - genetics; Deoxyribonucleic acid; DNA; DNA methylation; DNA Methylation - genetics; Epigenesis, Genetic; Epigenetics; Epigenome - genetics; Epigenomics; Ethnic factors; Female; Gene expression; Genome-wide association studies; Genomes; Health risks; Hispanic or Latino; Humans; Leukocytes; Leukocytes - cytology; Lipids; Lipids - blood; Lipoproteins, HDL - blood; Male; Medicin och hälsovetenskap; Middle Aged; Minority & ethnic groups; Quantitative trait loci; Quantitative Trait Loci - genetics; Risk analysis; Risk factors; Triglycerides; White People
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-23899-y

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.