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Established BMI-associated genetic variants and their prospective associations with BMI and other cardiometabolic traits: the GLACIER Study
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Established BMI-associated genetic variants and their prospective associations with BMI and other cardiometabolic traits: the GLACIER Study
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Journal Article
Established BMI-associated genetic variants and their prospective associations with BMI and other cardiometabolic traits: the GLACIER Study
2016
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 45/43
/ 45/77
/ 692/163
/ 692/499
/ Alleles
/ Fasting
/ Female
/ Genetic Predisposition to Disease - epidemiology
/ Genetic Predisposition to Disease - genetics
/ Genome-Wide Association Study
/ Genomes
/ Genotype
/ Glaciers
/ Glucose
/ Health Promotion and Disease Prevention
/ Humans
/ Lipids
/ Loci
/ Male
/ Medical Genetics and Genomics (including Gene Therapy)
/ Medicine
/ Medicinsk genetik och genomik (Här ingår: Genterapi)
/ Medicinska och farmaceutiska grundvetenskaper
/ Obesity
/ Polymorphism, Single Nucleotide - genetics
/ Science
