Interaction between obesity-susceptibility loci in chromosome regions 2p25-p24 and 13q13-q21.
One of the chief complexities of genetic influences on human obesity appears to be gene-gene interactions. Here, we employed model-free approaches to look for gene-gene interaction effects in human obesity using genome scan data from 260 European American families. We found consistent evidence for statistical interaction between 2p25-p24 (18-38 cM) and 13q13-q21 (26-47 cM). For discrete traits, the positive correlations were significant at P<0.0001 (P</=0.0023 after correction for multiple tests) in both IBD-based and NPL-based analyses for BMI>/=40 kg/m(2). Other analytic approaches gave consistent, supportive results. For quantitative traits, interaction effects were significant for BMI (P=0.0012), percent fat (P=0.0265) and waist circumference (P=0.0023) in a Haseman-Elston regression model, and for BMI (P=0.0043) in variance component analysis. Our findings suggest that obesity-susceptibility loci in chromosome regions 2p25-p24 and 13q13-21 may interact to influence extreme human obesity. The identification of gene-gene interactions may prove crucial to understanding the contributions of genes, which, by themselves, have relatively small effects on obesity susceptibility and resistance.
Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
Chuanhui
C
Dong
Wei-Dong
WD
Li
Ding
D
Li
R Arlen
RA
Price
D015992:Body Mass Index; D002874:Chromosome Mapping; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D004198:Disease Susceptibility; D004843:Epistasis, Genetic; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D008126:Lod Score; D009765:Obesity / Q000235:genetics*; D040641:Quantitative Trait Loci / Q000235:genetics*; D019655:Quantitative Trait, Heritable; D035781:Siblings; D044465:White People
D005819:Genetic Markers