Genotype by smoking interaction for leptin levels in the San Antonio Family Heart Study.
Recent studies reported a marked inverse effect of smoking on serum levels of leptin (an adipocyte derived protein), offering a possible explanation for variation in body weight between smokers and non-smokers. The goal of this study was to examine the genetic architecture of the response to smoking in leptin levels using data from the San Antonio Family Heart Study. We employed a variance decomposition analysis using maximum likelihood methods to model genotype by smoking interactions for leptin levels, examined the impact of the exclusion of smokers in a subsequent linkage analysis, and incorporated the QTL identified in the linkage analysis in a model of genotype by smoking interaction. We found significant evidence (P = 0.001) for a genotype by smoking status interaction for serum leptin levels. In the subsequent linkage analysis with smokers excluded, we obtained a maximum LOD score of 3.1 (P = 0.00008) near D8S1102. Using this QTL in a model of genotype by smoking status interaction, we identified significant evidence for an interaction at this specific locus (P = 0.04). Given these results, we hypothesize that a quantitative trait locus in this vicinity of chromosome 8 may have a differential effect on the expression of leptin in smokers versus non-smokers.
Martin
Lisa J
LJ
Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, Texas 78245-0549, USA. lmartin@darwin.sfbr.org
Cole
Shelley A
SA
Hixson
James E
JE
Mahaney
Michael C
MC
Czerwinski
Stefan A
SA
Almasy
Laura
L
Blangero
John
J
Comuzzie
Anthony G
AG
D000328:Adult; D002898:Chromosomes, Human, Pair 8; D004777:Environment; D005260:Female; D005787:Gene Frequency; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D020738:Leptin / Q000097:blood*; D016013:Likelihood Functions; D008126:Lod Score; D008297:Male; D017058:Mexican Americans; D008875:Middle Aged; D010641:Phenotype; D016133:Polymerase Chain Reaction; D019655:Quantitative Trait, Heritable; D011863:Radioimmunoassay; D012907:Smoking / Q000097:blood*; D013781:Texas
D020738:Leptin