Original Article

International Journal of Obesity (2008) 32, 930–935; doi:10.1038/ijo.2008.23; published online 4 March 2008

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

J B Wilk1,2, J M Laramie1,3, J C Latourelle1, S Williamson1, M W Nagle1, J E Tobin1,4, C L Foster5, J H Eckfeldt5, M A Province6, I B Borecki6 and R H Myers1,2

  1. 1Department of Neurology, Boston University School of Medicine, Boston, MA, USA
  2. 2Department of Medicine, Section of Preventive Medicine and Epidemiology, Boston University School of Medicine, Boston, MA, USA
  3. 3Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA
  4. 4Department of Anatomy, Physiology, and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
  5. 5Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA
  6. 6Center for Human Genome Sciences, Washington University School of Medicine, St Louis, MO, USA

Correspondence: Dr JB Wilk, Department of Neurology, Boston University School of Medicine, 715 Albany Street, E-338 Boston, MA 02118, USA. E-mail: jwilk@bu.edu

Received 21 October 2007; Revised 31 January 2008; Accepted 5 February 2008; Published online 4 March 2008.

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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.

Keywords:

leptin, single nucleotide polymorphism, association

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