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Genetic Association with Lipids in Filipinos: Waist Circumference Modifies an APOA5 Effect on Triglyceride Levels

Citation

Wu, Ying; Marvelle, Amanda F.; Li, Jin; Croteau-Chonka, Damien C.; Feranil, Alan B.; Kuzawa, Christopher W.; Li, Yun; Adair, Linda S.; & Mohlke, Karen L. (2013). Genetic Association with Lipids in Filipinos: Waist Circumference Modifies an APOA5 Effect on Triglyceride Levels. Journal of Lipid Research, 54(11), 3198-3205. PMCID: PMC3793624

Abstract

Blood levels of lipoprotein cholesterol and triglycerides (TG) 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 (CLHNS), 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 x 10-8) were detected at APOE for low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC), and at APOA5 for TG. Suggestive associations (P < 10-6) were detected at GCKR for TG, and at CETP and TOM1 for high-density lipoprotein cholesterol (HDL-C). Our data also supported the existence of allelic heterogeneity at APOA5, CETP, LIPC and APOE. The secondary signal (Gly185Cys) at APOA5 exhibited a SNP-by-waist circumference interaction affecting TG (Pinteraction = 1.6 x 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 that APOA5 signal, emphasizing that CVD risk could be reduced by central obesity control.

URL

http://dx.doi.org/10.1194/jlr.P042077

Reference Type

Journal Article

Year Published

2013

Journal Title

Journal of Lipid Research

Author(s)

Wu, Ying
Marvelle, Amanda F.
Li, Jin
Croteau-Chonka, Damien C.
Feranil, Alan B.
Kuzawa, Christopher W.
Li, Yun
Adair, Linda S.
Mohlke, Karen L.

PMCID

PMC3793624