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Inverse relationship between a genetic risk score of 31 BMI loci and weight change before and after reaching middle age
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2016 (English)In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 40, no 2, 252-259 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND/OBJECTIVE: Genome-wide-association studies have identified numerous body mass index (BMI)-associated variants, but it is unclear how these relate to weight gain in adults at different ages.

METHODS: We examined the association of a genetic risk score (GRS), consisting of 31 BMI-associated variants, with an annual weight change (AWC) and a substantial weight gain (SWG) of 10% by comparing self-reported weight at 20 years (y) with baseline weight (mean: 58 y; s.d.: 8 y) in 21407 participants from the Malmö Diet and Cancer Study (MDCS), and comparing baseline weight to weight at follow-up (mean: 73 y; s.d.: 6 y) among 2673 participants. Association between GRS and AWG and SWG was replicated in 4327 GLACIER (Gene x Lifestyle interactions And Complex traits Involved in Elevated disease Risk) participants (mean: 45 y; s.d.: 7 y) with 10 y follow-up. Cohort-specific results were pooled by fixed-effect meta-analyses.

RESULTS: In MDCS, the GRS was associated with increased AWC (β: 0.003; s.e: 0.01; P: 7 × 10(-8)) and increased odds for SWG (odds ratio (OR) 1.01 (95% confidence interval (CI): 1.00, 1.02); P: 0.013) per risk-allele from age 20y, but unexpectedly with decreased AWC (β: -0.006; s.e: 0.002; P: 0.009) and decreased odds for SWG OR 0.96 (95% CI: 0.93, 0.98); P: 0.001) between baseline and follow-up. Effect estimates from age 20 y to baseline differed significantly from those from baseline to follow-up (P: 0.0002 for AWC and P: 0.0001 for SWG). Similar to MDCS, the GRS was associated with decreased odds for SWG OR 0.98 (95% CI: 0.96, 1.00); P: 0.029) from baseline to follow-up in GLACIER. In meta-analyses (n=7000), the GRS was associated with decreased AWC (β: -0.005; s.e.m. 0.002; P: 0.002) and decreased odds for SWG OR 0.97 (95% CI: 0.96, 0.99); P: 0.001) per risk-allele.

CONCLUSIONS: Our results provide convincing evidence for a paradoxical inversed relationship between a high number of BMI-associated risk-alleles and less weight gain during and after middle-age, in contrast to the expected increased weight gain seen in younger age.

Place, publisher, year, edition, pages
2016. Vol. 40, no 2, 252-259 p.
National Category
Endocrinology and Diabetes Medical Genetics
URN: urn:nbn:se:umu:diva-116976DOI: 10.1038/ijo.2015.180ISI: 000369691500010PubMedID: 26374450OAI: diva2:903674

Special Issue: All roads lead to the brain

Available from: 2016-02-16 Created: 2016-02-16 Last updated: 2016-06-15Bibliographically approved

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Stocks, TanjaFranks, Paul W
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Urology and AndrologyDepartment of Biobank ResearchMedicine
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