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Adiposity and Genetic Factors in Relation to Triglycerides and Triglyceride-Rich Lipoproteins in the Women's Genome Health Study
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA; Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Clinical Research Centre, Lund University, Skåne University Hospital, Malmö, Sweden.
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2018 (English)In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 64, no 1, p. 231-241Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Previous results from Scandinavian cohorts have shown that obesity accentuates the effects of common genetic susceptibility variants on increased triglycerides (TG). Whether such interactions are present in the US population and further selective for particular TG-rich lipoprotein subfractions is unknown.

METHODS: We examined these questions using body mass index (BMI) and waist circumference (WC) among women of European ancestry from the Women's Genome Health Study (WGHS) (n = 21840 for BMI; n = 19313 for WC). A weighted genetic risk score (TG-wGRS) based on 40 published TG-associated single-nucleotide polymorphisms was calculated using published effect estimates.

RESULTS: Comparing overweight (BMI ≥ 25 kg/m2) and normal weight (BMI < 25 kg/m2) WGHS women, each unit increase of TG-wGRS was associated with TG increases of 1.013% and 1.011%, respectively, and this differential association was significant (Pinteraction = 0.014). Metaanalyses combining results for WGHS BMI with the 4 Scandinavian cohorts (INTER99, HEALTH2006, GLACIER, MDC) (total n = 40026) yielded a more significant interaction (Pinteraction = 0.001). Similarly, we observed differential association of the TG-wGRS with TG (Pinteraction = 0.006) in strata of WC (<80 cm vs ≥80 cm). Metaanalysis with 2 additional cohorts reporting WC (INTER99 and HEALTH2006) (total n = 27834) was significant with consistent effects (Pinteraction = 0.006). We also observed highly significant interactions of the TG-wGRS across the strata of BMI with very large, medium, and small TG-rich lipoprotein subfractions measured by nuclear magnetic resonance spectroscopy (all Pinteractions < 0.0001). The differential effects were strongest for very large TG-rich lipoprotein.

CONCLUSIONS: Our results support the original findings and suggest that obese individuals may be more susceptible to aggregated genetic risk associated with common TG-raising alleles, with effects accentuated in the large TG-rich lipoprotein subfraction.

Place, publisher, year, edition, pages
2018. Vol. 64, no 1, p. 231-241
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Medical Genetics
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URN: urn:nbn:se:umu:diva-144095DOI: 10.1373/clinchem.2017.280545ISI: 000419121500031PubMedID: 29097515OAI: oai:DiVA.org:umu-144095DiVA, id: diva2:1178522
Available from: 2018-01-30 Created: 2018-01-30 Last updated: 2018-06-09Bibliographically approved

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Franks, Paul W.

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