Integrative Biology

Established BMI-associated genetic variants and their prospective associations with BMI and other cardiometabolic traits: the GLACIER Study

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Abstract

Background:

Recent cross-sectional genome-wide scans have reported associations of 97 independent loci with body mass index (BMI). In 3541 middle-aged adult participants from the GLACIER Study, we tested whether these loci are associated with 10-year changes in BMI and other cardiometabolic traits (fasting and 2-h glucose, triglycerides, total cholesterol, and systolic and diastolic blood pressures).

Methods:

A BMI-specific genetic risk score (GRS) was calculated by summing the BMI-associated effect alleles at each locus. Trait-specific cardiometabolic GRSs comprised only the loci that show nominal association (P0.10) with the respective trait in the original cross-sectional study. In longitudinal genetic association analyses, the second visit trait measure (assessed ~10 years after baseline) was used as the dependent variable and the models were adjusted for the baseline measure of the outcome trait, age, age2, fasting time (for glucose and lipid traits), sex, follow-up time and population substructure.

Results:

The BMI-specific GRS was associated with increased BMI at follow-up (β=0.014 kg m−2 per allele per 10-year follow-up, s.e.=0.006, P=0.019) as were three loci (PARK2 rs13191362, P=0.005; C6orf106 rs205262, P=0.043; and C9orf93 rs4740619, P=0.01). Although not withstanding Bonferroni correction, a handful of single-nucleotide polymorphisms was nominally associated with changes in blood pressure, glucose and lipid levels.

Conclusions:

Collectively, established BMI-associated loci convey modest but statistically significant time-dependent associations with long-term changes in BMI, suggesting a role for effect modification by factors that change with time in this population.

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Acknowledgements

We thank the participants and staff from the GLACIER Study. The current study was supported by Novo Nordisk (to PWF), the Swedish Research Council (to PWF), the Swedish Heart Lung Foundation (to PWF), European Research Council (to PWF) and the Skåne Health Authority (to PWF). This study was also supported by a postdoctoral grant from the Basque Government (to AP). Shafqat Ahmad has received travel grants from the Swedish Heart-Lung Foundation and Royal Physiographic Society of Lund, Sweden, to present this work at the 75th Scientific Sessions of the American Diabetes Association, Boston, USA.

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Correspondence to P W Franks.

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Competing interests

PWF has received consulting honoraria from Ely Lilly Inc. and Sanofi Aventis, as well as research support from Novo Nordisk, Ely Lilly and Sanofi Aventis, but none of these affect the integrity or interpretation of the research data reported herein. The remaining authors declare no conflict of interest.

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