Effects of smoking on the genetic risk of obesity: the population architecture using genomics and epidemiology study

BMC Med Genet. 2013 Jan 11;14:6. doi: 10.1186/1471-2350-14-6.

Abstract

Background: Although smoking behavior is known to affect body mass index (BMI), the potential for smoking to influence genetic associations with BMI is largely unexplored.

Methods: As part of the 'Population Architecture using Genomics and Epidemiology (PAGE)' Consortium, we investigated interaction between genetic risk factors associated with BMI and smoking for 10 single nucleotide polymorphisms (SNPs) previously identified in genome-wide association studies. We included 6 studies with a total of 56,466 subjects (16,750 African Americans (AA) and 39,716 European Americans (EA)). We assessed effect modification by testing an interaction term for each SNP and smoking (current vs. former/never) in the linear regression and by stratified analyses.

Results: We did not observe strong evidence for interactions and only observed two interactions with p-values <0.1: for rs6548238/TMEM18, the risk allele (C) was associated with BMI only among AA females who were former/never smokers (β = 0.018, p = 0.002), vs. current smokers (β = 0.001, p = 0.95, p(interaction) = 0.10). For rs9939609/FTO, the A allele was more strongly associated with BMI among current smoker EA females (β = 0.017, p = 3.5 x 10(-5)), vs. former/never smokers (β = 0.006, p = 0.05, p(interaction) = 0.08).

Conclusions: These analyses provide limited evidence that smoking status may modify genetic effects of previously identified genetic risk factors for BMI. Larger studies are needed to follow up our results.

Clinical trial registration: NCT00000611.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • African Americans / genetics
  • Aged
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • Body Mass Index*
  • European Continental Ancestry Group / genetics
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Membrane Proteins / genetics
  • Middle Aged
  • Obesity / epidemiology
  • Obesity / genetics*
  • Polymorphism, Single Nucleotide*
  • Proteins / genetics
  • Risk Factors
  • Smoking / adverse effects*
  • Smoking / genetics
  • Young Adult

Substances

  • Membrane Proteins
  • Proteins
  • TMEM18 protein, human
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • FTO protein, human

Associated data

  • ClinicalTrials.gov/NCT00000611

Grant support