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

Ahmad, S. LU ; Poveda, A. LU ; Shungin, D. LU ; Barroso, I.; Hallmans, G.; Renström, F. LU and Franks, P. W. LU (2016) In International Journal of Obesity
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 (P⩽0.10) with the respective trait in the original cross-sectional study. In longitudinal genetic association analyses, the second... (More)

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, 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.International Journal of Obesity advance online publication, 7 June 2016; doi:10.1038/ijo.2016.72.

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International Journal of Obesity
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Nature Publishing Group
external identifiers
  • Scopus:84976329754
ISSN
0307-0565
DOI
10.1038/ijo.2016.72
language
English
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yes
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753df6f8-03b2-4387-911e-fda0ebb64299
date added to LUP
2016-07-20 10:34:35
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2016-10-27 13:02:25
@misc{753df6f8-03b2-4387-911e-fda0ebb64299,
  abstract     = {<p>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<sup>2</sup>, 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<sup>-2</sup> 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.International Journal of Obesity advance online publication, 7 June 2016; doi:10.1038/ijo.2016.72.</p>},
  author       = {Ahmad, S. and Poveda, A. and Shungin, D. and Barroso, I. and Hallmans, G. and Renström, F. and Franks, P. W.},
  issn         = {0307-0565},
  language     = {eng},
  month        = {06},
  publisher    = {ARRAY(0x84f7040)},
  series       = {International Journal of Obesity},
  title        = {Established BMI-associated genetic variants and their prospective associations with BMI and other cardiometabolic traits : the GLACIER Study},
  url          = {http://dx.doi.org/10.1038/ijo.2016.72},
  year         = {2016},
}