BMI loci and longitudinal BMI from adolescence to young adulthood in an ethnically diverse cohort

• Published in: International Journal of Obesity Vol. 41; no. 5; pp. 759 - 768
• Main Authors: Graff, M, North, K E, Richardson, A S, Young, K L, Mazul, A L, Highland, H M, Mohlke, K L, Lange, L A, Lange, E M, Mullan Harris, K, Gordon-Larsen, P
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-05-2017; Nature Publishing Group
• Subjects: 631/208; 631/208/457/649; 631/443; 692/699/2743/393; 692/700/139/2818; 692/700/478/174; Adolescent; Adolescents; African Americans; Age differences; Alpha-Ketoglutarate-Dependent Dioxygenase FTO - genetics; Analysis; AP-2 protein; Body Mass Index; Body size; Child development; Cohort Studies; Data collection; Demographic aspects; DNA-Binding Proteins - genetics; Epidemiology; Ethnic Groups - genetics; Female; Genetic aspects; Genetic Loci - genetics; Genetic Predisposition to Disease - genetics; Genetic Variation; Genome-Wide Association Study; Genomes; Health aspects; Health Promotion and Disease Prevention; Humans; Internal Medicine; Loci; Longitudinal studies; Male; Medicine; Medicine & Public Health; Membrane Proteins - genetics; Meta-analysis; Metabolic Diseases; Mitochondrial Membrane Transport Proteins - genetics; National Longitudinal Study of Adolescent Health; Nucleotides; Obesity; Obesity - epidemiology; Obesity - genetics; original-article; Physiological aspects; Polymorphism, Single Nucleotide; Public Health; Receptor, Melanocortin, Type 4 - genetics; Risk factors; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Systematic review; Transcription Factor AP-2 - genetics; United States - epidemiology; Weight Gain - genetics; Weight Gain - physiology; Young Adult; United States
• ISSN: 0307-0565; 1476-5497
• DOI: 10.1038/ijo.2016.233

Objective:
The association of obesity susceptibility variants with change in body mass index (BMI) across the life course is not well understood.
Subjects:
In ancestry-stratified models of 5962 European American (EA), 2080 African American (AA) and 1582 Hispanic American (HA) individuals from the National Longitudinal Study of Adolescent to Adult Health (Add Health), we examined associations between 34 obesity single-nucleotide polymorphisms (SNPs) with per year change in BMI, measured by the slope from a growth-curve analysis of two or more BMI measurements between adolescence and young adulthood. For SNPs nominally associated with BMI change (
P
<0.05), we interrogated age differences within data collection Wave and time differences between age categories that overlapped between Waves.
Results:
We found SNPs in/near
FTO, MC4R, MTCH2, TFAP2B, SEC16B and TMEM18
were significantly associated (
P
<0.0015≈0.05/34) with BMI change in EA and the ancestry-combined meta-analysis. rs9939609 in
FTO
met genome-wide significance at
P
<5e−08 in the EA and ancestry-combined analysis, respectively [Beta(se)=0.025(0.004);Beta(se)=0.021(0.003)]. No SNPs were significant after Bonferroni correction in AA or HA, although five SNPs in AA and four SNPs in HA were nominally significant (
P
<0.05). In EA and the ancestry-combined meta-analysis, rs3817334 near
MTCH2
showed larger effects in younger respondents, whereas rs987237 near
TFAP2B
, showed larger effects in older respondents across all Waves. Differences in effect estimates across time for
MTCH2
and
TFAP2B
are suggestive of either era or cohort effects.
Conclusion:
The observed association between variants in/near
FTO, MC4R, MTCH2, TFAP2B, SEC16B and TMEM18
with change in BMI from adolescence to young adulthood suggest that the genetic effect of BMI loci varies over time in a complex manner, highlighting the importance of investigating loci influencing obesity risk across the life course.