Do Genetic Factors Modify the Relationship Between Obesity and Hypertriglyceridemia? : Findings From the GLACIER and the MDC Studies
(2016) In Circulation: Cardiovascular Genetics 9(2). p.162-171- 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... (More)
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.
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- author
- Ali, Ashfaq LU ; V Varga, Tibor LU ; Stojkovic, Ivana LU ; Schulz, Christina-Alexandra LU ; Hallmans, Göran ; Barroso, Inês ; Poveda, Alaitz LU ; Renström, Frida LU ; Orho-Melander, Marju LU and Franks, Paul LU
- organization
- publishing date
- 2016-02-10
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- bioinformatics, genetic epidemiology, genetics, obesity, triglycerides
- in
- Circulation: Cardiovascular Genetics
- volume
- 9
- issue
- 2
- pages
- 10 pages
- publisher
- American Heart Association
- external identifiers
-
- pmid:26865658
- scopus:84966318831
- pmid:26865658
- wos:000374795800010
- ISSN
- 1942-325X
- DOI
- 10.1161/CIRCGENETICS.115.001218
- language
- English
- LU publication?
- yes
- id
- 733994f1-1a03-4edc-8e8b-71d029a7cb29 (old id 8825779)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/26865658?dopt=Abstract
- date added to LUP
- 2016-04-04 07:06:08
- date last changed
- 2022-04-07 22:08:52
@article{733994f1-1a03-4edc-8e8b-71d029a7cb29, abstract = {{<p>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.</p><p>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.</p><p>CONCLUSIONS: Our findings provide evidence that body fatness accentuates the effects of genetic susceptibility variants in hypertriglyceridemia, effects that are most evident in females.</p>}}, author = {{Ali, Ashfaq and V Varga, Tibor and Stojkovic, Ivana and Schulz, Christina-Alexandra and Hallmans, Göran and Barroso, Inês and Poveda, Alaitz and Renström, Frida and Orho-Melander, Marju and Franks, Paul}}, issn = {{1942-325X}}, keywords = {{bioinformatics; genetic epidemiology; genetics; obesity; triglycerides}}, language = {{eng}}, month = {{02}}, number = {{2}}, pages = {{162--171}}, publisher = {{American Heart Association}}, series = {{Circulation: Cardiovascular Genetics}}, title = {{Do Genetic Factors Modify the Relationship Between Obesity and Hypertriglyceridemia? : Findings From the GLACIER and the MDC Studies}}, url = {{http://dx.doi.org/10.1161/CIRCGENETICS.115.001218}}, doi = {{10.1161/CIRCGENETICS.115.001218}}, volume = {{9}}, year = {{2016}}, }