Stratification by Smoking Status Reveals an Association of Genotype with Body Mass Index in Never Smokers

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We found that a single nucleotide polymorphism in the CHRNA5-A3-B4 gene cluster, which is known to influence smoking heaviness, is associated with lower body mass index (BMI) in current smokers, but higher BMI in never smokers. This difference in effects suggests that the variant influences BMI both via pathways other than smoking, and via the weight-reducing effects of smoking, in opposite directions. The overall effect on BMI would therefore be undetectable in an unstratified genome-wide association study, indicating that novel associations may be obscured by hidden population sub-structure.

Vyšlo v časopise: Stratification by Smoking Status Reveals an Association of Genotype with Body Mass Index in Never Smokers. PLoS Genet 10(12): e32767. doi:10.1371/journal.pgen.1004799
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004799

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1. SpeliotesEK, WillerCJ, BerndtSI, MondaKL, ThorleifssonG, et al. (2010) Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nat Genet 42: 937–948.

2. BhojaniFA, TsaiSP, WendtJK, KollerKL (2014) Simulating the impact of changing trends in smoking and obesity on productivity of an industrial population: an observational study. BMJ Open 4: e004788.

3. WareJJ, van den BreeMB, MunafoMR (2011) Association of the CHRNA5-A3-B4 gene cluster with heaviness of smoking: a meta-analysis. Nicotine Tob Res 13: 1167–1175.

4. FreathyRM, KazeemGR, MorrisRW, JohnsonPC, PaternosterL, et al. (2011) Genetic variation at CHRNA5-CHRNA3-CHRNB4 interacts with smoking status to influence body mass index. Int J Epidemiol 40: 1617–1628.

5. KeskitaloK, BromsU, HeliovaaraM, RipattiS, SurakkaI, et al. (2009) Association of serum cotinine level with a cluster of three nicotinic acetylcholine receptor genes (CHRNA3/CHRNA5/CHRNB4) on chromosome 15. Hum Mol Genet 18: 4007–4012.

6. MunafoMR, TimofeevaMN, MorrisRW, Prieto-MerinoD, SattarN, et al. (2012) Association between genetic variants on chromosome 15q25 locus and objective measures of tobacco exposure. J Natl Cancer Inst 104: 740–748.

7. Davey SmithG (2011) Use of genetic markers and gene-diet interactions for interrogating population-level causal influences of diet on health. Genes Nutr 6: 27–43.

8. Davey SmithG, EbrahimS (2003) 'Mendelian randomization': can genetic epidemiology contribute to understanding environmental determinants of disease? Int J Epidemiol 32: 1–22.

9. Tobacco-and-Genetics-Consortium (2010) Genome-wide meta-analyses identify multiple loci associated with smoking behavior. Nat Genet 42: 441–447.

10. FraylingTM, TimpsonNJ, WeedonMN, ZegginiE, FreathyRM, et al. (2007) A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 316: 889–894.

11. MunafoMR, JohnstoneEC, WaltherD, UhlGR, MurphyMF, et al. (2011) CHRNA3 rs1051730 genotype and short-term smoking cessation. Nicotine Tob Res 13: 982–988.

12. GlymourMM, Tchetgen TchetgenEJ, RobinsJM (2012) Credible Mendelian randomization studies: approaches for evaluating the instrumental variable assumptions. Am J Epidemiol 175: 332–339.

13. AmosCI, WuX, BroderickP, GorlovIP, GuJ, et al. (2008) Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1. Nat Genet 40: 616–622.

14. WareJJ, van den BreeM, MunafoMR (2012) From men to mice: CHRNA5/CHRNA3, smoking behavior and disease. Nicotine Tob Res 14: 1291–1299.

15. BierutLJ, StitzelJA, WangJC, HinrichsAL, GruczaRA, et al. (2008) Variants in nicotinic receptors and risk for nicotine dependence. Am J Psychiatry 165: 1163–1171.

16. FowlerCD, LuQ, JohnsonPM, MarksMJ, KennyPJ (2011) Habenular alpha5 nicotinic receptor subunit signalling controls nicotine intake. Nature 471: 597–601.

17. GruczaRA, WangJC, StitzelJA, HinrichsAL, SacconeSF, et al. (2008) A risk allele for nicotine dependence in CHRNA5 is a protective allele for cocaine dependence. Biol Psychiatry 64: 922–929.

18. HallforsJ, LoukolaA, PitkaniemiJ, BromsU, MannistoS, et al. (2013) Scrutiny of the CHRNA5-CHRNA3-CHRNB4 smoking behavior locus reveals a novel association with alcohol use in a Finnish population based study. Int J Mol Epidemiol Genet 4: 109–119.

19. MineurYS, AbizaidA, RaoY, SalasR, DiLeoneRJ, et al. (2011) Nicotine decreases food intake through activation of POMC neurons. Science 332: 1330–1332.

20. TimpsonNJ, NordestgaardBG, HarbordRM, ZachoJ, FraylingTM, et al. (2011) C-reactive protein levels and body mass index: elucidating direction of causation through reciprocal Mendelian randomization. Int J Obes (Lond) 35: 300–308.

21. MurcrayCE, LewingerJP, GaudermanWJ (2009) Gene-environment interaction in genome-wide association studies. Am J Epidemiol 169: 219–226.

22. HancockDB, ArtigasMS, GharibSA, HenryA, ManichaikulA, et al. (2012) Genome-wide joint meta-analysis of SNP and SNP-by-smoking interaction identifies novel loci for pulmonary function. PLoS Genet 8: e1003098.