Genetic association with lipids in Filipinos: waist circumference modifies an APOA5 effect on triglyceride levels.

Abstract:

: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)-by-waist 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.

journal_name

J Lipid Res

authors

Wu Y,Marvelle AF,Li J,Croteau-Chonka DC,Feranil AB,Kuzawa CW,Li Y,Adair LS,Mohlke KL

doi

10.1194/jlr.P042077

subject

Has Abstract

pub_date

2013-11-01 00:00:00

pages

3198-205

issue

11

eissn

0022-2275

issn

1539-7262

pii

jlr.P042077

journal_volume

54

pub_type

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