Original Paper

Analysis of 30 Genes (355 SNPS) Related to Energy Homeostasis for Association with Adiposity in European-American and Yup'ik Eskimo Populations
Wendy K. Chung^{a, b}, Amit Patki^c, Naoki Matsuoka^{a, b}, Bert B. Boyer^d, Nianjun Liu^c, Solomon K. Musani^c, Anna V. Goropashnaya^d, Perciliz L. Tan^e, Nicholas Katsanis^e, Stephen B. Johnson^a, Peter K. Gregersen^f, David B. Allison^c, Rudolph L. Leibel^{a, b}, Hemant K. Tiwari<sup>c

a</sup>Columbia University Medical Center, New York, NY,
^bNaomi Berrie Diabetes Center, New York, NY,
^cUniversity of Alabama at Birmingham, Birmingham, Ala.,
^dUniversity of Alaska Fairbanks, Fairbanks, Alaska,
^eJohns Hopkins University, Baltimore, Md., and
^fFeinstein Institute for Medical Research, Manhasset, NY, USA

Address of Corresponding Author

Hum Hered 2009;67:193-205 (DOI: 10.1159/000181158)

  Key Words

• Obesity
• Body composition
• Body mass index
• Candidate gene
• Ghrelin

  Abstract

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.

Copyright © 2008 S. Karger AG, Basel

  Author Contacts

Wendy K. Chung
Columbia University Medical Center
1150 St. Nicholas Avenue, Room 620
New York, NY 10032 (USA)
Tel. +1 212 851 5313, Fax +1 212 851 5306, E-Mail wkc15@columbia.edu

  Article Information

Received: February 19, 2008
Accepted after revision: July 10, 2008
Published online: December 15, 2008
Number of Print Pages : 13
Number of Figures : 4, Number of Tables : 8, Number of References : 43