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Implication of European-derived adiposity loci in African Americans

International Journal of Obesity volume 36, pages 465–473 (2012)Cite this article

Abstract

Objective:

Recent genome-wide association studies (GWAS) have identified multiple novel loci associated with adiposity in European-derived study populations. Limited study of these loci has been reported in African Americans. Here we examined the effects of these previously identified adiposity loci in African Americans.

Methods:

A total of 46 representative single-nucleotide polymorphisms (SNPs) in 19 loci that were previously reported in GWAS in Europeans (including FTO and MC4R) were genotyped in 4992 subjects from six African-American cohorts. These SNPs were tested for association with body mass index (BMI) after adjustment for age, gender, disease status and population structure in each cohort. Meta-analysis was conducted to combine the results.

Results:

Meta-analysis of 4992 subjects revealed seven SNPs near four loci, including NEGR1, TMEM18, SH2B1 /ATP2A1 and MC4R, showing significant association at 0.005<P<0.05, and had effect sizes between 0.04 and 0.06 s.d. units (or 0.30 to 0.44 kg m−2) of BMI for each copy of the BMI-increasing allele. The most significantly associated SNPs (rs9424977, rs3101336 and rs2568958) are located in the NEGR1 gene (P=0.005, 0.020 and 0.019, respectively).

Conclusion:

We replicated the association of variants at four loci in six African-American cohorts that demonstrated a consistent direction of association with previous studies of adiposity in Europeans. These loci are all highly expressed in the brain, consistent with an important role for central nervous system processes in weight regulation. However, further comprehensive examination of these regions may be necessary to fine map and elucidate for possible genetic differences between these two populations.

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Acknowledgements

We thank the study subjects for their participation. Genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University, contract number HHSC268200782096C. This work was supported by NIH Grants R01 DK087914 (MCYN), R01 DK066358 (DWB), R01 DK053591 (DWB), R01 HL56266 (BIF), R01 DK070941 (BIF), R01 HL060944 (LW), R01 HL061210 (MB), K99 DK081350 (NDP) and by the Wake Forest University School of Medicine Grant M01 RR07122 and Venture Fund (MCYN).

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Authors and Affiliations

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

    J M Hester, M R Wing, J Li, N D Palmer, J Xu, P J Hicks, B H Roh, D W Bowden & M C Y Ng

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

    J M Hester, M R Wing, J Li, N D Palmer, J Xu, P J Hicks, B H Roh, D W Bowden & M C Y Ng

  3. Program in Molecular Genetics and Genomics, Wake Forest University School of Medicine, Winston-Salem, NC, USA

    J M Hester & M R Wing

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

    N D Palmer, P J Hicks, B H Roh & D W Bowden

  5. Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Aurora, C, O, USA

    J M Norris

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

    L E Wagenknecht

  7. Department of Biostatistical Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA

    C D Langefeld

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

    B I Freedman & D W Bowden

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  1. J M Hester
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  2. M R Wing
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  3. J Li
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Correspondence to M C Y Ng.

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Hester, J., Wing, M., Li, J. et al. Implication of European-derived adiposity loci in African Americans. Int J Obes 36, 465–473 (2012). https://doi.org/10.1038/ijo.2011.131

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