TY - JOUR
T1 - Genetic association with lipids in Filipinos
T2 - Waist circumference modifies an APOA5 effect on triglyceride levels
AU - Wu, Ying
AU - Marvelle, Amanda F.
AU - Li, Jin
AU - Croteau-Chonka, Damien C.
AU - Feranil, Alan B.
AU - Kuzawa, Christopher W.
AU - Li, Yun
AU - Adair, Linda S.
AU - Mohlke, Karen L.
PY - 2013/11
Y1 - 2013/11
N2 - 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.
AB - 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.
KW - Genome-wide association
KW - Interaction
KW - Lipid traits
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U2 - 10.1194/jlr.P042077
DO - 10.1194/jlr.P042077
M3 - Article
C2 - 24023260
AN - SCOPUS:84885972487
SN - 0022-2275
VL - 54
SP - 3198
EP - 3205
JO - Journal of lipid research
JF - Journal of lipid research
IS - 11
ER -