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Replication of the association of common rs9939609 variant of FTO with increased BMI in an Australian adult twin population but no evidence for gene by environment (G × E) interaction

International Journal of Obesity volume 33, pages 75–79 (2009)Cite this article

Abstract

Objective:

To further investigate a common variant (rs9939609) in the fat mass- and obesity-associated gene (FTO), which recent genome-wide association studies have shown to be associated with body mass index (BMI) and obesity.

Design:

We examined the effect of this FTO variant on BMI in 3353 Australian adult male and female twins.

Results:

The minor A allele of rs9939609 was associated with an increased BMI (P=0.0007). Each additional copy of the A allele was associated with a mean BMI increase of ∼1.04 kg/m2 (∼3.71 kg). Using variance components decomposition, we estimate that this single-nucleotide polymorphism accounts for ∼3% of the genetic variance in BMI in our sample (∼2% of the total variance). By comparing intrapair variances of monozygotic twins of different genotypes we were able to perform a direct test of gene by environment (G × E) interaction in both sexes and gene by parity (G × P) interaction in women, but no evidence was found for either.

Conclusions:

In addition to supporting earlier findings that the rs9939609 variant in the FTO gene is associated with an increased BMI, our results indicate that the associated genetic effect does not interact with environment or parity.

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References

  1. Dunstan D, Zimmer P, Welborn T, Sicree R, Armstrong T, Atkins R et al. Diabesity and Associated Disorders in Australia - 2000: The Accelerating Epidemic, in The Australian Diabetes, Obesity and Lifestyle Study (AusDiab). 2001, International Diabetes Institute: Melbourne, Australia, http://www.diabetes.com.au/pdf/AusDiab_Report.pdf.

  2. Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, Lindgren CM et al. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 2007; 316: 889–894.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Andreasen CH, Stender-Petersen KL, Mogensen MS, Torekov SS, Wegner L, Andersen G et al. Low physical activity accentuates the effect of the FTO rs9939609 polymorphism on body fat accumulation. Diabetes 2008; 57: 95–101.

    Article  CAS  PubMed  Google Scholar 

  4. Scuteri A, Sanna S, Chen WM, Uda M, Albai G, Strait J et al. Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLoS Genet 2007; 3: e115.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Dina C, Meyre D, Gallina S, Durand E, Korner A, Jacobson P et al. Variation in FTO contributes to childhood obesity and severe adult obesity. Nat Genet 2007; 39: 724–726.

    Article  CAS  PubMed  Google Scholar 

  6. Wahlen K, Sjolin E, Hoffstedt J . The common rs9939609 gene variant of the fat mass and obesity associated gene (FTO) is related to fat cell lipolysis. J Lipid Res 2007; 12: 12.

    Google Scholar 

  7. Cornes BK, Medland SE, Ferreira MA, Morley KI, Duffy DL, Heijmans BT et al. Sex-limited genome-wide linkage scan for body mass index in an unselected sample of 933 Australian twin families. Twin Res Hum Genet 2005; 8: 616–632.

    Article  PubMed  Google Scholar 

  8. Bucholz KK, Cadoret R, Cloninger CR, Dinwiddie SH, Hesselbrock VM, Nurnberger Jr JI et al. A new, semi-structured psychiatric interview for use in genetic linkage studies: a report on the reliability of the SSAGA. J Stud Alcohol 1994; 55: 149–158.

    Article  CAS  PubMed  Google Scholar 

  9. Heath AC, Bucholz KK, Madden PA, Dinwiddie SH, Slutske WS, Bierut LJ et al. Genetic and environmental contributions to alcohol dependence risk in a national twin sample: consistency of findings in women and men. Psychol Med 1997; 27: 1381–1396.

    Article  CAS  PubMed  Google Scholar 

  10. Abecasis GR, Cherny SS, Cookson WO, Cardon LR . Merlin—rapid analysis of dense genetic maps using sparse gene flow trees. Nat Genet 2002; 30: 97–101.

    Article  CAS  PubMed  Google Scholar 

  11. Wigginton JE, Abecasis GR . PEDSTATS: descriptive statistics, graphics and quality assessment for gene mapping data. Bioinformatics 2005; 21: 3445–3447.

    Article  CAS  PubMed  Google Scholar 

  12. Fisher RA . The Resemblance between Twins, a Statistical Examination of Lauterbach's Measurements. Genetics 1925; 10: 569–579.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Levene H . Robust tests for the equality of variances. In Olkin I (ed). Contributions to Probability and Statistics: Essays in Honor of Harold Hotelling 1960. Stanford University Press: Palo Alto, CA, pp 278–292.

    Google Scholar 

  14. Abecasis GR, Cardon LR, Cookson WO . A general test of association for quantitative traits in nuclear families. Am J Hum Genet 2000; 66: 279–292.

    Article  CAS  PubMed  Google Scholar 

  15. Fulker DW, Cherny SS, Sham PC, Hewitt JK . Combined linkage and association sib-pair analysis for quantitative traits. Am J Hum Genet 1999; 64: 259–267.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Posthuma D, de Geus EJ, Boomsma DI, Neale MC . Combined linkage and association tests in mx. Behav Genet 2004; 34: 179–196.

    Article  CAS  PubMed  Google Scholar 

  17. Terwilliger JD . Inflated false-positive rates in Hardy–Weinberg and linkage-equilibrium tests are due to sampling on the basis of rare familial phenotypes in finite populations. Am J Hum Genet 2000; 67: 258–259.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Hosking L, Lumsden S, Lewis K, Yeo A, McCarthy L, Bansal A et al. Detection of genotyping errors by Hardy–Weinberg equilibrium testing. Eur J Hum Genet 2004; 12: 395–399.

    Article  CAS  PubMed  Google Scholar 

  19. Gutersohn A, Naber C, Muller N, Erbel R, Siffert W . G protein beta3 subunit 825 TT genotype and post-pregnancy weight retention. Lancet 2000; 355: 1240–1241.

    Article  CAS  PubMed  Google Scholar 

  20. Barber TM, Bennett AJ, Groves CJ, Sovio U, Ruokonen A, Martikainen H et al. Association of variants in the fat mass and obesity associated (FTO) gene with polycystic ovary syndrome. Diabetologia 2008; 51: 1153–1158.

    Article  CAS  PubMed  Google Scholar 

  21. Wellcome Trust Case Control Consortium. Genome-wide association study of 14 000 cases of seven common diseases and 3000 shared controls. Nature 2007; 447: 661–678.

    Article  Google Scholar 

  22. Plomin R, DeFries JC, Loehlin JC . Genotype–environment interaction and correlation in the analysis of human behavior. Psychol Bull 1977; 84: 309–322.

    Article  CAS  PubMed  Google Scholar 

  23. Li H, Wu Y, Loos RJ, Hu FB, Liu Y, Wang J et al. Variants in FTO gene are not associated with obesity in a Chinese Han population. Diabetes 2008; 57: 264–268.

    Article  CAS  PubMed  Google Scholar 

  24. Ohashi J, Naka I, Kimura R, Natsuhara K, Yamauchi T, Furusawa T et al. FTO polymorphisms in oceanic populations. J Hum Genet 2007; 52: 1031–1035.

    Article  PubMed  Google Scholar 

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Acknowledgements

We thank the help and support provided by many individuals at the Queensland Institute of Medical Research including the interviewers and clerical and administrative support staff supervised by Dixie Statham; Scott Gordon, Harry Beeby and David Smyth for computer support and phenotype data management; the laboratory staff for genotype sample management and genotyping, Sri Shekar for a superb introduction to QTDT; and, most of all, the twins and their relatives for their willing participation in the study. This study was supported in part by grants from NIH grants AA07535, AA07728, AA10249 and DA00272, postdoctoral training grants DA07261, MH17104 and MH14677, as well as grants from the Australian National Health and Medical Council, the Australian Associated Brewers and US Alcohol Beverage Medical Research Foundation. BKC is supported by an NHMRC Public Health Scholarship (361302). SEM is supported by an NHMRC Sidney Sax Fellowship (443036).

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Authors and Affiliations

  1. Genetic Epidemiology Unit, Queensland Institute of Medical Research, Brisbane, Queensland, Australia

    B K Cornes, P A Lind, S E Medland, G W Montgomery, D R Nyholt & N G Martin

  2. Central Clinical Division, School of Medicine, University of Queensland, Brisbane, Queensland, Australia

    B K Cornes

  3. Virginia Institute of Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA

    S E Medland

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  1. B K Cornes
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Correspondence to B K Cornes.

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Cornes, B., Lind, P., Medland, S. et al. Replication of the association of common rs9939609 variant of FTO with increased BMI in an Australian adult twin population but no evidence for gene by environment (G × E) interaction. Int J Obes 33, 75–79 (2009). https://doi.org/10.1038/ijo.2008.223

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