Analysis of 30 Genes (355 SNPS) Related to Energy Homeostasis for Association with Adiposity in European-American and Yup’ik Eskimo Populations

Objective: Human adiposity is highly heritable, but few of the genes that predispose to obesity in most humans are known. We tested candidate genes in pathways related to food intake and energy expenditure for association with measures of adiposity. Methods: We studied 355 genetic variants in 30 can...

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Bibliographic Details
Published in:Human heredity 2009-01, Vol.67 (3), p.193-205
Main Authors: Chung, Wendy K., Patki, Amit, Matsuoka, Naoki, Boyer, Bert B., Liu, Nianjun, Musani, Solomon K., Goropashnaya, Anna V., Tan, Perciliz L., Katsanis, Nicholas, Johnson, Stephen B., Gregersen, Peter K., Allison, David B., Leibel, Rudolph L., Tiwari, Hemant K.
Format: Article
Language:English
Subjects:
Adiposity - genetics
Adult
Alaska
Body Composition - genetics
Body Mass Index
Comparative studies
Epistasis, Genetic
European Continental Ancestry Group - genetics
Female
Genetics
Ghrelin - genetics
Haplotypes
Humans
Inuits - genetics
Male
Middle Aged
Molecular biology
Native peoples
New York City
Obesity
Original Paper
Phenotype
Polymorphism, Single Nucleotide
Sequence Analysis, DNA
Skinfold Thickness
Waist Circumference - genetics
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Summary:Objective: Human adiposity is highly heritable, but few of the genes that predispose to obesity in most humans are known. We tested candidate genes in pathways related to food intake and energy expenditure for association with measures of adiposity. Methods: We studied 355 genetic variants in 30 candidate genes in 7 molecular pathways related to obesity in two groups of adult subjects: 1,982 unrelated European Americans living in the New York metropolitan area drawn from the extremes of their body mass index (BMI) distribution and 593 related Yup’ik Eskimos living in rural Alaska characterized for BMI, body composition, waist circumference, and skin fold thicknesses. Data were analyzed by using a mixed model in conjunction with a false discovery rate (FDR) procedure to correct for multiple testing. Results: After correcting for multiple testing, two single nucleotide polymorphisms (SNPs) in Ghrelin (GHRL) (rs35682 and rs35683) were associated with BMI in the New York European Americans. This association was not replicated in the Yup’ik participants. There was no evidence for gene × gene interactions among genes within the same molecular pathway after adjusting for multiple testing via FDR control procedure. Conclusion: Genetic variation in GHRL may have a modest impact on BMI in European Americans.
ISSN:0001-5652
1423-0062
DOI:10.1159/000181158