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

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.

• Authors: 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
• Journal: Circulation. Cardiovascular genetics (Circ Cardiovasc Genet) Vol. 9 Issue 2 Pg. 162-71 (Apr 2016) ISSN: 1942-3268 [Electronic] United States
• PMID: 26865658 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2016 American Heart Association, Inc.

Chemical References

• Triglycerides

Topics

• Body Mass Index
• Female
• Gene Regulatory Networks
• Genetic Predisposition to Disease
• Genome-Wide Association Study
• Humans
• Hypertriglyceridemia (blood, complications, genetics)
• Life Style
• Male
• Middle Aged
• Obesity (blood, complications, genetics)
• Polymorphism, Single Nucleotide (genetics)
• Risk Factors
• Sex Characteristics
• Triglycerides (blood)