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Analysis of FTO gene variants with obesity and glucose homeostasis measures in the multiethnic Insulin Resistance Atherosclerosis Study cohort

International Journal of Obesity volume 35, pages 1173–1182 (2011)Cite this article

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Abstract

Objective:

Previous studies have replicated the association of variants within FTO (fat mass- and obesity-associated) intron 1 with obesity and adiposity quantitative traits in populations of European ancestry. Non-European populations, however, have not been so intensively studied. The goal of this investigation was to examine the association of FTO single-nucleotide polymorphisms (SNPs), prominent in the literature in a multiethnic sample of non-Hispanic White American (n=458), Hispanic American (n=373) and African American (n=288) subjects from the Insulin Resistance Atherosclerosis Study (IRAS). This cohort provides the unique ability to evaluate how variation within FTO influences measures of adiposity and glucose homeostasis in three different ethnicities, which were ascertained and examined using a common protocol.

Design:

A total of 26 FTO SNPs were genotyped, including those consistently associated in the literature (rs9939609, rs8050136, rs1121980, rs1421085, rs17817449 and rs3751812), and tested for association with adiposity and glucose homeostasis traits.

Results:

For the adiposity phenotypes, these and other SNPs were associated with body mass index (BMI) in both non-Hispanic Whites (P-values ranging from 0.015 to 0.048) and Hispanic Americans (P-values ranging from 7.1 × 10−6 to 0.027). In Hispanic Americans, four other SNPs (rs8047395, rs10852521, rs8057044 and rs8044769) still showed evidence of association after multiple comparisons adjustment (P-values ranging from 5.0 × 10−5 to 5.2 × 10−4). The historically associated BMI SNPs were not associated in the African Americans, but rs1108102 was associated with BMI (P-value of 5.4 × 10−4) after accounting for multiple comparisons. For glucose homeostasis traits, associations were seen with acute insulin response in non-Hispanic Whites and African Americans. However, all associations with glucose homeostasis measures were no longer significant after adjusting for multiple comparisons.

Conclusion:

These results replicate the association of FTO intron 1 variants with BMI in non-Hispanic Whites and Hispanic Americans but show little evidence of association in African Americans, suggesting that the effect of FTO variants on adiposity phenotypes shows genetic heterogeneity dependent on ethnicity.

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Acknowledgements

This research was supported in part by NIH grants HL060894, HL060931, HL060944, HL061019 and HL061210. We acknowledge the support of the Wake Forest University Health Sciences Center for Public Health Genomics.

Author information

Authors and Affiliations

  1. Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC, USA

    M R Wing, B H Roh, N D Palmer & D W Bowden

  2. Center for Diabetes Research, Wake Forest University School of Medicine, Winston-Salem, NC, USA

    M R Wing, B H Roh, N D Palmer & D W Bowden

  3. Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC, USA

    M R Wing, B H Roh, N D Palmer & D W Bowden

  4. Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA

    J M Ziegler, C D Langefeld & L E Wagenknecht

  5. Department of Nutrition, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    E J Mayer-Davis

  6. Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Denver, CO, USA

    M J Rewers

  7. Division of Clinical Epidemiology, University of Texas Health Sciences Center at San Antonio, San Antonio, TX, USA

    S M Haffner

  8. Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA

    D W Bowden

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Correspondence to D W Bowden.

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Wing, M., Ziegler, J., Langefeld, C. et al. Analysis of FTO gene variants with obesity and glucose homeostasis measures in the multiethnic Insulin Resistance Atherosclerosis Study cohort. Int J Obes 35, 1173–1182 (2011). https://doi.org/10.1038/ijo.2010.244

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