title: Interaction of smoking and obesity susceptibility loci on adolescent BMI: The National Longitudinal Study of Adolescent to Adult Health.
abstract: BACKGROUND
  Adolescence is a sensitive period for weight gain and risky health behaviors, such as smoking. Genome-wide association studies (GWAS) have identified loci contributing to adult body mass index (BMI). Evidence suggests that many of these loci have a larger influence on adolescent BMI. However, few studies have examined interactions between smoking and obesity susceptibility loci on BMI. This study investigates the interaction of current smoking and established BMI SNPs on adolescent BMI. Using data from the National Longitudinal Study of Adolescent to Adult Health, a nationally-representative, prospective cohort of the US school-based population in grades 7 to 12 (12-20 years of age) in 1994-95 who have been followed into adulthood (Wave II 1996; ages 12-21, Wave III; ages 18-27), we assessed (in 2014) interactions of 40 BMI-related SNPs and smoking status with percent of the CDC/NCHS 2000 median BMI (%MBMI) in European Americans (n = 5075), African Americans (n = 1744) and Hispanic Americans (n = 1294).
  
  
  RESULTS
  Two SNPs showed nominal significance for interaction (p < 0.05) between smoking and genotype with %MBMI in European Americans (EA) (rs2112347 (POC5): β = 1.98 (0.06, 3.90), p = 0.04 and near rs571312 (MC4R): β 2.15 (-0.03, 4.33) p = 0.05); and one SNP showed a significant interaction effect after stringent correction for multiple testing in Hispanic Americans (HA) (rs1514175 (TNNI3K): β 8.46 (4.32, 12.60), p = 5.9E-05). Stratifying by sex, these interactions suggest a stronger effect in female smokers.
  
  
  CONCLUSIONS
  Our study highlights potentially important sex differences in obesity risk by smoking status in adolescents, with those who may be most likely to initiate smoking (i.e., adolescent females), being at greatest risk for exacerbating genetic obesity susceptibility.
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA. kristin.young@unc.edu.|Carolina Population Center, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA. kristin.young@unc.edu.|, 137 East Franklin Street, Suite 306, Chapel Hill, NC, 27514, USA. kristin.young@unc.edu.
authors.forename: Kristin 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. migraff@email.unc.edu.|Carolina Population Center, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA. migraff@email.unc.edu.
authors.forename: Misa
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. karinorth@unc.edu.|Carolina Center for Genome Sciences, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA. karinorth@unc.edu.
authors.forename: Kari E
authors.initials: KE
authors.lastname: North
authors.affiliation: Carolina Population Center, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA. anno.richardson@gmail.com.|Department of Nutrition, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA. anno.richardson@gmail.com.
authors.forename: Andrea S
authors.initials: AS
authors.lastname: Richardson
authors.affiliation: Carolina Center for Genome Sciences, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA. karen_mohlke@med.unc.edu.|Department of Genetics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA. karen_mohlke@med.unc.edu.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Mohlke
authors.affiliation: Carolina Center for Genome Sciences, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA. leslie_lange@med.unc.edu.|Department of Genetics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA. leslie_lange@med.unc.edu.
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Lange
authors.affiliation: Carolina Center for Genome Sciences, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA. ethan_lange@med.unc.edu.|Department of Genetics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA. ethan_lange@med.unc.edu.
authors.forename: Ethan M
authors.initials: EM
authors.lastname: Lange
authors.affiliation: Carolina Population Center, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA. kathie_harris@unc.edu.|Department of Sociology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA. kathie_harris@unc.edu.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Harris
authors.affiliation: Carolina Population Center, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA. pglarsen@unc.edu.|Department of Nutrition, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA. pglarsen@unc.edu.
authors.forename: Penny
authors.initials: P
authors.lastname: Gordon-Larsen
mesh_terms: D000293:Adolescent; D000067697:Adolescent Health; D015992:Body Mass Index; D005006:Ethnicity / Q000235:genetics; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009765:Obesity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012907:Smoking / Q000235:genetics*; D055815:Young Adult