Do Genetic Factors Modify the Relationship Between Obesity and Hypertriglyceridemia? Findings From the GLACIER and the MDC Studies

Ashfaq Ali, Tibor V Varga, Ivana A Stojkovic, Christina-Alexandra Schulz, Göran Hallmans, Inês Barroso, Alaitz Poveda, Frida Renström, Marju Orho-Melander, Paul W Franks

7 Citations (Scopus)

Abstract

BACKGROUND: Obesity is a major risk factor for dyslipidemia, but this relationship is highly variable. Recently published data from 2 Danish cohorts suggest that genetic factors may underlie some of this variability.

METHODS AND RESULTS: We tested whether established triglyceride-associated loci modify the relationship of body mass index (BMI) and triglyceride concentrations in 2 Swedish cohorts (the Gene-Lifestyle Interactions and Complex Traits Involved in Elevated Disease Risk [GLACIER Study; N=4312] and the Malmö Diet and Cancer Study [N=5352]). The genetic loci were amalgamated into a weighted genetic risk score (WGRSTG) by summing the triglyceride-elevating alleles (weighted by their established marginal effects) for all loci. Both BMI and the WGRSTG were strongly associated with triglyceride concentrations in GLACIER, with each additional BMI unit (kg/m(2)) associated with 2.8% (P=8.4×10(-84)) higher triglyceride concentration and each additional WGRSTG unit with 2% (P=7.6×10(-48)) higher triglyceride concentration. Each unit of the WGRSTG was associated with 1.5% higher triglyceride concentrations in normal weight and 2.4% higher concentrations in overweight/obese participants (Pinteraction=0.056). Meta-analyses of results from the Swedish cohorts yielded a statistically significant WGRSTG×BMI interaction effect (Pinteraction=6.0×10(-4)), which was strengthened by including data from the Danish cohorts (Pinteraction=6.5×10(-7)). In the meta-analysis of the Swedish cohorts, nominal evidence of a 3-way interaction (WGRSTG×BMI×sex) was observed (Pinteraction=0.03), where the WGRSTG×BMI interaction was only statistically significant in females. Using protein-protein interaction network analyses, we identified molecular interactions and pathways elucidating the metabolic relationships between BMI and triglyceride-associated loci.

CONCLUSIONS: Our findings provide evidence that body fatness accentuates the effects of genetic susceptibility variants in hypertriglyceridemia, effects that are most evident in females.

Original languageEnglish
JournalCirculation. Cardiovascular genetics
Volume9
Issue number2
Pages (from-to)162-71
Number of pages10
ISSN1942-325X
DOIs
Publication statusPublished - Apr 2016
Externally publishedYes

Keywords

  • Body Mass Index
  • Female
  • Gene Regulatory Networks
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Hypertriglyceridemia
  • Life Style
  • Male
  • Middle Aged
  • Obesity
  • Polymorphism, Single Nucleotide
  • Risk Factors
  • Sex Characteristics
  • Triglycerides
  • Journal Article
  • Research Support, Non-U.S. Gov't

Fingerprint

Dive into the research topics of 'Do Genetic Factors Modify the Relationship Between Obesity and Hypertriglyceridemia? Findings From the GLACIER and the MDC Studies'. Together they form a unique fingerprint.

Cite this