Ying Wu, Amanda F. Marvelle, Jin Li, Damien C. Croteau-Chonka, Alan B. Feranil, Christopher W. Kuzawa, Yun Li, Linda S. Adair, Karen L. Mohlke
Blood levels of lipoprotein cholesterol and triglycerides (TGs) are highly heritable and are major risk factors for cardiovascular disease (CVD). Approximately 100 lipid-associated loci have been identified in populations of European ancestry. We performed a genome-wide association study of lipid traits in 1,782 Filipino women from the Cebu Longitudinal Health and Nutrition Survey, and tested for evidence of interactions with waist circumference. We conducted additional association and interaction analyses in 1,719 of their young adult offspring. Genome-wide significant associations (P < 5 × 10 -8) were detected at APOE for low density lipoprotein cholesterol and total cholesterol, and at APOA5 for TGs. Suggestive associations (P < 10-6) were detected at GCKR for TGs, and at CETP and TOM1 for high density lipoprotein cholesterol. Our data also supported the existence of allelic heterogeneity at APOA5, CETP, LIPC, and APOE. The secondary signal (Gly185Cys) at APOA5 exhibited a single nucleotide polymorphism (SNP) -bywaist circumference interaction affecting TGs (Pinteraction = 1.6 × 10 -4), manifested by stronger SNP effects as waist circumference increased. These findings provide the first evidence that central obesity may accentuate the effect of the TG-increasing allele of the APOA5 signal, emphasizing that CVD risk could be reduced by central obesity control. Copyright © 2013 by the American Society for Biochemistry and Molecular Biology, Inc.
Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, United States; Department of Biostatistics, University of North Carolina, Chapel Hill, NC 27599, United States; Department of Computer Science, University of North Carolina, Chapel Hill, NC 27599, United States; Department of Nutrition, University of North Carolina, Chapel Hill, NC 27599, United States; Department of Curriculum in Bioinformatics and Computational Biology, University of North Carolina, Chapel Hill, NC 27599, United States; University of San Carlos-Office of Population Studies Foundation, University of San Carlos, Cebu City 6000, Philippines; Department of Anthropology, Northwestern University, Evanston, IL 60208, United States; Cells to Society: the Center for Social Disparities and Health at the Institute for Policy Research, Northwestern University, Evanston, IL 60208, United States
