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NYD-SP18 is associated with obesity in the NHLBI Family Heart Study

International Journal of Obesity volume 32, pages 930–935 (2008)Cite this article

Abstract

Objective:

The NHLBI Family Heart Study (FHS) genome-wide linkage scan identified a region of chromosome 7q with a logarithm of odds score of 4.9 for body mass index (BMI).

Design:

We report the results of fine mapping the linkage peak using 1020 single nucleotide polymorphisms (SNPs) to test for association to obesity in families exhibiting linkage to chromosome 7. Association observed in linked families (284 obese cases/381 controls) was examined in an independent set of unrelated FHS participants (172 obese cases/308 controls) to validate the observed association. Two dichotomous obesity phenotypes were studied based on clinical BMI cutoffs and the sex-specific distribution of both BMI and leptin levels.

Results:

Using a P-value of 0.01 as criteria for association in the linked families, a P-value of 0.05 as criteria for association in the unrelated sample, and requiring consistency in the direction of the effect of the minor allele between the two samples, we identified two coding SNPs in the NYD-SP18 gene with minor alleles increasing the risk of obesity. Adjustment for exercise, smoking and FTO genotype did not influence the result in linked families, but improved the result in the unrelated sample. Carrying a minor allele of the nonsynonymous SNP rs6971091 conferred an odds ratio of at least 2 for obesity defined by both BMI and leptin levels.

Conclusion:

The effect of the NYD-SP18 SNP on obesity was larger than the effect of FTO in FHS families. Publicly available results from genome-wide association studies support the association between NYD-SP18 and BMI. The NYD-SP18 gene is described as testes development related, but little is known about the gene's function or the mechanism by which it may influence risk for obesity.

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Acknowledgements

This study was supported by National Heart, Lung, and Blood Institute grants NHLBI RO-1 HL68891-06. This article is presented on behalf of the investigators of the NHLBI Family Heart Study.

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Authors and Affiliations

  1. Department of Neurology, Boston University School of Medicine, Boston, MA, USA

    J B Wilk, J M Laramie, J C Latourelle, S Williamson, M W Nagle, J E Tobin & R H Myers

  2. Department of Medicine, Section of Preventive Medicine and Epidemiology, Boston University School of Medicine, Boston, MA, USA

    J B Wilk & R H Myers

  3. Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA

    J M Laramie

  4. Department of Anatomy, Physiology, and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA

    J E Tobin

  5. Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA

    C L Foster & J H Eckfeldt

  6. Center for Human Genome Sciences, Washington University School of Medicine, St Louis, MO, USA

    M A Province & I B Borecki

Authors
  1. J B Wilk
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  2. J M Laramie
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  3. J C Latourelle
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  4. S Williamson
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  5. M W Nagle
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  6. J E Tobin
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  7. C L Foster
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  8. J H Eckfeldt
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  9. M A Province
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  10. I B Borecki
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  11. R H Myers
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Correspondence to J B Wilk.

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Wilk, J., Laramie, J., Latourelle, J. et al. NYD-SP18 is associated with obesity in the NHLBI Family Heart Study. Int J Obes 32, 930–935 (2008). https://doi.org/10.1038/ijo.2008.23

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  • DOI: https://doi.org/10.1038/ijo.2008.23

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