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

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*

*Corresponding author for this work

Research output: Contribution to journalArticle

20 Scopus citations

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) -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.

Original languageEnglish (US)
Pages (from-to)3198-3205
Number of pages8
JournalJournal of lipid research
Volume54
Issue number11
DOIs
StatePublished - Nov 2013

Keywords

  • Genome-wide association
  • Interaction
  • Lipid traits

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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    Wu, Y., Marvelle, A. F., Li, J., Croteau-Chonka, D. C., Feranil, A. B., Kuzawa, C. W., Li, Y., Adair, L. S., & Mohlke, K. 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. https://doi.org/10.1194/jlr.P042077