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 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 x gene interactions among genes within the same molecular pathway after adjusting for multiple testing via FDR control procedure.


CONCLUSIONS
Genetic variation in GHRL may have a modest impact on BMI in European Americans.
Chung
Wendy K
WK
Columbia University Medical Center, New York, NY 10032, USA. wkc15@columbia.edu
Patki
Amit
A
Matsuoka
Naoki
N
Boyer
Bert B
BB
Liu
Nianjun
N
Musani
Solomon K
SK
Goropashnaya
Anna V
AV
Tan
Perciliz L
PL
Katsanis
Nicholas
N
Johnson
Stephen B
SB
Gregersen
Peter K
PK
Allison
David B
DB
Leibel
Rudolph L
RL
Tiwari
Hemant K
HK
D050154:Adiposity / Q000235:genetics*; D000328:Adult; D000413:Alaska; D001823:Body Composition / Q000235:genetics; D015992:Body Mass Index; D004843:Epistasis, Genetic; D005260:Female; D054439:Ghrelin / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D004930:Inuit / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009519:New York City; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D012885:Skinfold Thickness; D055105:Waist Circumference / Q000235:genetics; D044465:White People / Q000235:genetics*
C515349:GHRL protein, human; D054439:Ghrelin