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Photo: KG Pressfoto

Marju Orho-Melander

Professor

Photo: KG Pressfoto

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

Author

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

Summary, in English

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.

Department/s

  • Genetic and Molecular Epidemiology
  • Diabetes - Cardiovascular Disease
  • EXODIAB: Excellence of Diabetes Research in Sweden
  • EpiHealth: Epidemiology for Health

Publishing year

2016-02-10

Language

English

Pages

162-171

Publication/Series

Circulation: Cardiovascular Genetics

Volume

9

Issue

2

Document type

Journal article

Publisher

American Heart Association

Topic

  • Medical Genetics

Keywords

  • bioinformatics
  • genetic epidemiology
  • genetics
  • obesity
  • triglycerides

Status

Published

Research group

  • Genetic and Molecular Epidemiology
  • Diabetes - Cardiovascular Disease

ISBN/ISSN/Other

  • ISSN: 1942-325X