title: BMI loci and longitudinal BMI from adolescence to young adulthood in an ethnically diverse cohort.
abstract: The association of obesity susceptibility variants with change in body mass index (BMI) across the life course is not well understood.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: M
authors.initials: M
authors.lastname: Graff
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.|Carolina Center for Genome Sciences, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: K E
authors.initials: KE
authors.lastname: North
authors.affiliation: RAND Corporation, Santa Monica, CA, USA.
authors.forename: A S
authors.initials: AS
authors.lastname: Richardson
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.|Carolina Population Center, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Young
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: A L
authors.initials: AL
authors.lastname: Mazul
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: H M
authors.initials: HM
authors.lastname: Highland
authors.affiliation: Carolina Center for Genome Sciences, University of North Carolina, Chapel Hill, NC, USA.|Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Mohlke
authors.affiliation: Carolina Center for Genome Sciences, University of North Carolina, Chapel Hill, NC, USA.|Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Lange
authors.affiliation: Carolina Center for Genome Sciences, University of North Carolina, Chapel Hill, NC, USA.|Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: E M
authors.initials: EM
authors.lastname: Lange
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.|Carolina Center for Genome Sciences, University of North Carolina, Chapel Hill, NC, USA.|Department of Sociology, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: K
authors.initials: K
authors.lastname: Mullan Harris
authors.affiliation: Carolina Population Center, University of North Carolina, Chapel Hill, NC, USA.|Department of Nutrition, Gillings School of Global Public Health, School of Medicine, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: P
authors.identifier: 0000-0001-5322-4188
authors.initials: P
authors.lastname: Gordon-Larsen
mesh_terms: D000293:Adolescent; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO / Q000235:genetics; D015992:Body Mass Index; D015331:Cohort Studies; D004268:DNA-Binding Proteins / Q000235:genetics; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D056426:Genetic Loci / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D033681:Mitochondrial Membrane Transport Proteins / Q000235:genetics; D063588:National Longitudinal Study of Adolescent Health; D009765:Obesity / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D044105:Receptor, Melanocortin, Type 4 / Q000235:genetics; D050656:Transcription Factor AP-2 / Q000235:genetics; D014481:United States / Q000453:epidemiology; D015430:Weight Gain / Q000235:genetics / Q000502:physiology; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; C470072:MC4R protein, human; C502207:MTCH2 protein, human; D008565:Membrane Proteins; D033681:Mitochondrial Membrane Transport Proteins; D044105:Receptor, Melanocortin, Type 4; C443860:SEC16B protein, human; C493677:TFAP2B protein, human; C530715:TMEM18 protein, human; D050656:Transcription Factor AP-2; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human