title: Genetic risk score and adiposity interact to influence triglyceride levels in a cohort of Filipino women.
abstract: OBJECTIVE
  Individually, genetic variants only moderately influence cardiometabolic (CM) traits, such as lipid and inflammatory markers. In this study we generated genetic risk scores from a combination of previously reported variants influencing CM traits, and used these scores to explore how adiposity levels could mediate genetic contributions to CM traits.
  
  
  METHODS
  Participants included 1649 women from the 2005 Cebu Longitudinal Health and Nutrition Survey. Three genetic risk scores were constructed for C-reactive protein (CRP), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TGs). We used linear regression models to assess the association between each genetic risk score and its related trait. We also tested for interactions between each score and measures of adiposity.
  
  
  RESULTS
  Each genetic risk score explained a greater proportion of variance in trait levels than any individual genetic variant. We found an interaction between the TG genetic risk score (2.29-14.34 risk alleles) and waist circumference (WC) (Pinteraction=1.66 × 10(-2)). Based on model predictions, for individuals with a higher TG genetic risk score (75th percentile=12), having an elevated WC (⩾80 cm) increased TG levels from 1.32 to 1.71 mmol l(-1). However, for individuals with a lower score (25th percentile=7), having an elevated WC did not significantly change TG levels.
  
  
  CONCLUSIONS
  The TG genetic risk score interacted with adiposity to synergistically influence TG levels. For individuals with a genetic predisposition to elevated TG levels, our results suggest that reducing adiposity could possibly prevent further increases in TG levels and thereby lessen the likelihood of adverse health outcomes such as cardiovascular disease.
authors.affiliation: Public Health Sciences Division, Cancer Prevention, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: N
authors.initials: N
authors.lastname: Zubair
authors.affiliation: Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: E J
authors.initials: EJ
authors.lastname: Mayer-Davis
authors.affiliation: Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Mendez
authors.affiliation: Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Mohlke
authors.affiliation: Department of Epidemiology and Carolina Center for Genome Sciences, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: K E
authors.initials: KE
authors.lastname: North
authors.affiliation: Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: L S
authors.initials: LS
authors.lastname: Adair