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

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

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 as...

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Bibliographic Details
Published in:International Journal of Obesity Vol. 32; no. 6; pp. 930 - 935
Main Authors: Wilk, J.B, Laramie, J.M, Latourelle, J.C, Williamson, S, Nagle, M.W, Tobin, J.E, Foster, C.L, Eckfeldt, J.H, Province, M.A, Borecki, I.B
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 01-06-2008
Nature Publishing
Nature Publishing Group
Subjects:
alleles
Biological and medical sciences
Body fat
Body Mass Index
Chromosome Mapping
Chromosomes
Chromosomes, Human, Pair 7 - genetics
Epidemiologic Methods
Epidemiology
exercise
Female
Gene Expression - genetics
Genes
Genetic aspects
Genetic Linkage
genetic markers
genetic polymorphism
genome
Genomes
Genotype
Health Promotion and Disease Prevention
Heart
Humans
Independent sample
Internal Medicine
Leptin
Leptin - metabolism
linkage (genetics)
Male
Medical sciences
Medicine
Medicine & Public Health
Metabolic Diseases
Middle Aged
NHLBI Family Health Study
Obesity
Obesity - genetics
original-article
phenotype
Physiological aspects
Polymorphism, Single Nucleotide - genetics
Public Health
Risk factors
single nucleotide polymorphism
Single nucleotide polymorphisms
smoking (habit)
United States
United States > US
single nucleotide polymorphism
association
leptin
Obesity
Genetic variability
Nutrition
Leptin
Nutrition disorder
Genotype
Metabolic diseases
Circulatory system
Adipokine
Single nucleotide polymorphism
Nutritional status
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Summary: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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SourceType-Scholarly Journals-1
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content type line 23
ISSN:0307-0565
1476-5497
DOI:10.1038/ijo.2008.23