Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Pediatric Original Article
  • Published:

The association of variants in the FTO gene with longitudinal body mass index profiles in non-Hispanic white children and adolescents

International Journal of Obesity volume 36, pages 61–68 (2012)Cite this article

Abstract

OBJECTIVE:

To investigate possible age-related changes in associations between polymorphisms in the fat mass and obesity-associated (FTO) gene and higher body mass index (BMI).

DESIGN AND SUBJECTS:

Multilevel mixed regression models were used to examine associations between four FTO variants and longitudinal BMI profiles in non-Hispanic white and African American children and adolescents 8–17 years of age from two different longitudinal cohort studies, the Bogalusa Heart Study (BHS) and Project HeartBeat! (PHB). In the BHS, there were 1551 examinations of 478 African Americans and 3210 examinations of 1081 non-Hispanic whites; in PHB, there were 971 examinations of 131 African Americans and 4458 examinations of 505 non-Hispanic whites.

RESULTS:

In African Americans, no significant FTO associations with BMI were found. In non-Hispanic whites, linkage disequilibrium among all four variants made haplotype analysis superfluous, so we focused on the single-nucleotide polymorphism, rs9939609. In longitudinal multilevel models, the A/A genotype of rs9939609 was associated with higher BMI in non-Hispanic whites in both cohorts at all ages. A significant age-by-genotype interaction found only in the BHS cohort predicted that in those with the A/A genotype, BMI would be ∼0.7 kg m−2 higher at age 8 and ∼1.6 kg m−2 higher at age 17 than in those with A/T or T/T genotypes. The design of PHB limited follow-up of any single individual to 4 years, and may have reduced the ability to detect any age-by-genotype interaction in this cohort.

CONCLUSIONS:

The A/A genotype of rs9939609 in the FTO gene is associated with higher longitudinal BMI profiles in non-Hispanic whites from two different cohorts. The association may change with age, with the A/A genotype being associated with a larger BMI difference in late adolescence than in childhood, though this was observed only in the BHS cohort and requires verification.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. 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  Google Scholar 

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

    Article  CAS  Google Scholar 

  3. Cecil JE, Tavendale R, Watt P, Hetherington MM, Palmer CNA . An obesity-associated FTO gene variant and increased energy intake in children. N Engl J Med 2008; 359: 2558–2566.

    Article  CAS  Google Scholar 

  4. Timpson NJ, Emmett PM, Frayling TM, Rogers I, Hattersley AT, McCarthy MI et al. The fat mass- and obesity-associated locus and dietary intake in children. Am J Clin Nutr 2008; 88: 971–978.

    Article  CAS  Google Scholar 

  5. Zhao J, Bradfield JP, Li M, Wang K, Zhang H, Kim CE et al. The role of obesity-associated loci identified in genome-wide association studies in the determination of pediatric BMI. Obesity (Silver Spring) 2009; 17: 2254–2257.

    Article  Google Scholar 

  6. Cha SW, Choi SM, Kim KS, Park BL, Kim JR, Kim JY et al. Replication of the genetic effects of FTO polymorphisms on BMI in a Korean population. Obesity (Silver Spring) 2008; 16: 2187–2189.

    Article  CAS  Google Scholar 

  7. Chang Y-C, Liu P-H, Lee W-J, Chang T-J, Jiang Y-D, Li H-Y et al. Common variation in the fat mass and obesity-associated (FTO) gene confers risk of obesity and modulates BMI in the Chinese population. Diabetes 2008; 57: 2245–2252.

    Article  CAS  Google Scholar 

  8. Hotta K, Nakata Y, Matsuo T, Kamohara S, Kotani K, Komatsu R et al. Variations in the FTO gene are associated with severe obesity in the Japanese. J Hum Genet 2008; 53: 546–553.

    Article  CAS  Google Scholar 

  9. Marvelle AF, Lange LA, Qin L, Adair LS, Mohlke KL . Association of FTO with obesity-related traits in the Cebu Longitudinal Health and Nutrition Survey (CLHNS) cohort. Diabetes 2008; 57: 1987–1991.

    Article  CAS  Google Scholar 

  10. Ng MCY, Park KS, Oh B, Tam CHT, Cho YM, Shin HD et al. Implication of genetic variants near TCF7L2, SLC30A8, HHEX, CDKAL1, CDKN2A/B, IGF2BP2, and FTO in type 2 diabetes and obesity in 6719 Asians. Diabetes 2008; 57: 2226–2233.

    Article  CAS  Google Scholar 

  11. Tan JT, Dorajoo R, Seielstad M, Sim XL, Ong RT, Chia KS et al. FTO variants are associated with obesity in the Chinese and Malay populations in Singapore. Diabetes 2008; 57: 2851–2857.

    Article  CAS  Google Scholar 

  12. 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  Google Scholar 

  13. Horikawa Y, Miyake K, Yasuda K, Enya M, Hirota Y, Yamagata K et al. Replication of genome-wide association studies of type 2 diabetes susceptibility in Japan. J Clin Endocrinol Metab 2008; 93: 3136–3141.

    Article  CAS  Google Scholar 

  14. Li H, Wu Y, Loos RJF, Hu FB, Liu Y, Wang J et al. Variants in the Fat Mass- and Obesity-associated (FTO) gene are not associated with obesity in a Chinese Han population. Diabetes 2008; 57: 264–268.

    Article  CAS  Google Scholar 

  15. Grant SFA, Li M, Bradfield JP, Kim CE, Annaiah K, Santa E et al. Association analysis of the FTO gene with obesity in children of Caucasian and African ancestry reveals a common tagging SNP. PLoS ONE 2008; 3: e1746.

    Article  Google Scholar 

  16. Hennig BJ, Fulford AJ, Sirugo G, Rayco-Solon P, Hattersley AT, Frayling TM et al. FTO gene variation and measures of body mass in an African population. BMC Med Genet 2009; 10: 21.

    Article  Google Scholar 

  17. Scuteri A, Sanna S, Chen W-M, 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  Google Scholar 

  18. Adeyemo A, Chen G, Zhou J, Shriner D, Doumatey A, Huang H et al. FTO genetic variation and association with obesity in West Africans and African Americans. Diabetes 2010; 59: 1549–1554.

    Article  CAS  Google Scholar 

  19. Hakanen M, Raitakari OT, Lehtimäki T, Peltonen N, Pahkala K, Sillanmäki L et al. FTO genotype is associated with body mass index after the age of seven years but not with energy intake or leisure-time physical activity. J Clin Endocrinol Metab 2009; 94: 1281–1287.

    Article  CAS  Google Scholar 

  20. López-Bermejo A, Petry CJ, Diaz M, Sebastiani G, de Zegher F, Dunger DB et al. The association between the FTO gene and fat mass in humans develops by the postnatal age of two weeks. J Clin Endocrinol Metab 2008; 93: 1501–1505.

    Article  Google Scholar 

  21. Wardle J, Llewellyn C, Sanderson S, Plomin R . The FTO gene and measured food intake in children. Int J Obes 2009; 33: 42–45.

    Article  CAS  Google Scholar 

  22. Haworth CMA, Carnell S, Meaburn EL, Davis OSP, Plomin R, Wardle J . Increasing heritability of BMI and stronger associations with the FTO gene over childhood. Obesity (Silver Spring) 2008; 16: 2663–2668.

    Article  Google Scholar 

  23. Jacobsson JA, Danielsson P, Svensson V, Klovins J, Gyllenstein U, Marcus C et al. Major gender differences in association of FTO gene variant among severely obese children with obesity and obesity related phenotypes. Biochem Biophys Res Comm 2008; 368: 476–482.

    Article  CAS  Google Scholar 

  24. Berenson GS, McMahan CA, Voors AW, Webber LS, Srinivasan SR, Frank GC et al. Cardiovascular Risk Factors in Children. The Early Natural History of Atherosclerosis and Essential Hypertension. Oxford University Press: New York, 1980.

    Google Scholar 

  25. Labarthe DR, Nichaman MZ, Harrist RB, Grunbaum JA, Dai S, for the Project HeartBeat! Investigators. Development of cardiovascular risk factors from ages 8 to 18 in Project HeartBeat! Study design and patterns of change in plasma total cholesterol concentration. Circulation 1997; 95: 2636–2642.

    Article  CAS  Google Scholar 

  26. Hallman DM, Srinivasan SR, Elkasabany A, Boerwinkle E, Berenson GS . The Ser 447 -Stop polymorphism of lipoprotein lipase is associated with variation in longitudinal serum high-density lipoprotein-cholesterol profiles: The Bogalusa Heart Study. Metabolism 2001; 50: 894–904.

    Article  CAS  Google Scholar 

  27. Hallman DM, Srinivasan SR, Chen W, Boerwinkle E, Berenson GS . The beta(2)-adrenergic receptor Arg16-Gly polymorphism and interactions involving beta(2)- and beta(3)-adrenergic receptor polymorphisms are associated with variations in longitudinal serum lipid profiles: The Bogalusa Heart Study. Metabolism 2004; 53: 1184–1191.

    Article  CAS  Google Scholar 

  28. Cronk CE, Roche AF, Kent R, Berkey C, Reed RB, Valadian I et al. Longitudinal trends and continuity in weight/stature2 from 3 months to 18 years. Hum Biol 1982; 54: 729–749.

    CAS  PubMed  Google Scholar 

  29. Hlaing WM, Prineas RJ, Zhu Y, Leaverton PE . Body mass index growth in a sample of US children: repeated measures data analysis of the Minneapolis Children's Blood Pressure Study. Am J Human Biol 2001; 13: 821–831.

    Article  CAS  Google Scholar 

  30. Guo SS, Huang C, Maynard LM, Demerath E, Towne B, Chumlea WC et al. Body mass index during childhood, adolescence and young adulthood in relation to adult overweight and adiposity: the Fels Longitudinal Study. Int J Obes 2000; 24: 1628–1635.

    Article  CAS  Google Scholar 

  31. Jess T, Zimermann E, Kring SII, Berentzen T, Holst C, Toubro S et al. Impact on weight dynamics and general growth of the common FTO rs9939609: a Longitudinal Danish Cohort Study. Int J Obes 2008; 32: 1388–1394.

    Article  CAS  Google Scholar 

  32. Hardy R, Wills AK, Wong A, Elks CE, Wareham NJ, Loos RJF et al. Life course variations in the associations between FTO and MC4R gene variants and body size. Hum Mol Genet 2010; 19: 545–552.

    Article  CAS  Google Scholar 

  33. Qi L, Kang K, Zhang C, van Dam RM, Kraft P, Hunter D et al. Fat mass- and obesity-associated (FTO) gene variant is associated with obesity. Longitudinal analyses in two cohort studies and functional test. Diabetes 2008; 57: 3145–3151.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Heart, Lung and Blood Institute grants HL070568 and HL089472 and the National Institute of Diabetes and Digestive and Kidney Diseases grant DK073618 (to DMH) and by the National Institute of Child Health and Human Development grants HD061437 and HD062783, the National Institute on Aging grant AG016592, and the American Heart Association grant 0855082E (to GSB). We wish to express our gratitude to the subjects and staff members of the PHB and the BHS.

Author information

Author notes

  1. R B Harrist: Deceased.

Authors and Affiliations

  1. Human Genetics Center, University of Texas School of Public Health, Houston, TX, USA

    D M Hallman, V C Friedel & E Boerwinkle

  2. Department of Pediatrics, University of Texas Medical School, Houston, TX, USA

    M A H Eissa

  3. Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA

    E Boerwinkle

  4. Department of Epidemiology and Biostatistics, School of Rural Public Health, Texas A&M University, College Station, TX, USA

    J C Huber Jr

  5. Division of Biostatistics, University of Texas School of Public Health, Austin, TX, USA

    R B Harrist

  6. Department of Epidemiology, Center for Cardiovascular Health, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA

    S R Srinivasan, W Chen & G S Berenson

  7. Division for Heart Disease and Stroke Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA

    S Dai & D R Labarthe

Authors
  1. D M Hallman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. V C Friedel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M A H Eissa
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. E Boerwinkle
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J C Huber Jr
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. R B Harrist
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. S R Srinivasan
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. W Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. S Dai
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. D R Labarthe
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. G S Berenson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to D M Hallman.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies the paper on International Journal of Obesity website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hallman, D., Friedel, V., Eissa, M. et al. The association of variants in the FTO gene with longitudinal body mass index profiles in non-Hispanic white children and adolescents. Int J Obes 36, 61–68 (2012). https://doi.org/10.1038/ijo.2011.190

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ijo.2011.190

Keywords

This article is cited by

Search

Advanced search

Quick links