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

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

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

Mark

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 (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.

(Less)

Please use this url to cite or link to this publication: https://lup.lub.lu.se/record/8825779

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

Medical Genetics

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}},
}

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