Publication

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

Journal Paper/Review - Apr 28, 2016

Units
PubMed
Doi

Citation
Ahmad S, Poveda A, Shungin D, Barroso I, Hallmans G, Renström F, Franks P. Established BMI-associated genetic variants and their prospective associations with BMI and other cardiometabolic traits: the GLACIER Study. Int J Obes (Lond) 2016; 40:1346-52.
Type
Journal Paper/Review (English)
Journal
Int J Obes (Lond) 2016; 40
Publication Date
Apr 28, 2016
Issn Electronic
1476-5497
Pages
1346-52
Brief description/objective

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 (P⩽0.10) 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, age(2), 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.