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


Graff, Mariaelisa; North, Kari E.; Richardson, Andrea S.; Young, Kristin L.; Mazul, Angela L.; Highland, Heather; Mohlke, Karen L.; Lange, Leslie A.; Lange, Ethan M.; & Harris, Kathleen M., et al. (2017). BMI loci and longitudinal BMI from adolescence to young adulthood in an ethnically diverse cohort. International Journal of Obesity. vol. 41 (5) pp. 759-768


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 approximately 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.


Reference Type

Journal Article

Journal Title

International Journal of Obesity


Graff, Mariaelisa
North, Kari E.
Richardson, Andrea S.
Young, Kristin L.
Mazul, Angela L.
Highland, Heather
Mohlke, Karen L.
Lange, Leslie A.
Lange, Ethan M.
Harris, Kathleen M.
Gordon-Larsen, Penny

Year Published


Volume Number


Issue Number





December 27, 2016





Reference ID