Genome-wide association study identifies polymorphisms in LEPR as determinants of plasma soluble leptin receptor levels
Open Access
- 17 February 2010
- journal article
- research article
- Published by Oxford University Press (OUP) in Human Molecular Genetics
- Vol. 19 (9), 1846-1855
- https://doi.org/10.1093/hmg/ddq056
Abstract
Plasma soluble leptin receptor (sOB-R) levels were inversely associated with diabetes risk factors, including adiposity and insulin resistance, and highly correlated with the expression levels of leptin receptor, which is ubiquitously expressed in most tissues. We conducted a genome-wide association study of sOB-R in 1504 women of European ancestry from the Nurses' Health Study. The initial scan yielded 26 single nucleotide polymorphisms (SNPs) significantly associated with sOB-R levels (P < 5 × 10−8); all mapping to the leptin receptor gene (LEPR). Analysis of imputed genotypes on autosomal chromosomes revealed an additional 106 SNPs in and adjacent to this gene that reached genome-wide significance level. Of these 132 SNPs (including two non-synonymous SNPs, rs1137100 and rs1137101), rs2767485, rs1751492 and rs4655555 remained associated with sOB-R levels at the 0.05 level (P = 9.1 × 10−9, 0.0105 and 0.0267, respectively) after adjustment for other univariately associated SNPs in a forward selection procedure. Significant associations with these SNPs were replicated in an independent sample of young males (n = 875) residing in Cyprus (P < 1 × 10−4). These data provide novel evidence revealing the role of polymorphisms in LEPR in modulating plasma levels of sOB-R and may further our understanding of the complex relationships among leptin, leptin receptor and diabetes-related traits.This publication has 43 references indexed in Scilit:
- Leptin and Soluble Leptin Receptor Levels in Plasma and Risk of Type 2 Diabetes in U.S. WomenDiabetes, 2009
- Integrated genotype calling and association analysis of SNPs, common copy number polymorphisms and rare CNVsNature Genetics, 2008
- A genome-wide association study of global gene expressionNature Genetics, 2007
- PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage AnalysesAmerican Journal of Human Genetics, 2007
- Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthmaNature, 2007
- High-resolution genomic profiling of chromosomal aberrations using Infinium whole-genome genotypingGenome Research, 2006
- Principal components analysis corrects for stratification in genome-wide association studiesNature Genetics, 2006
- A single nucleotide polymorphism (SNP) in the leptin receptor is associated with BMI, fat mass and leptin levels in postmenopausal Caucasian womenHuman Genetics, 2001
- Leptin—Much More Than a Satiety SignalAnnual Review of Nutrition, 2000
- Leptin Induces Insulin-like Signaling That Antagonizes cAMP Elevation by Glucagon in HepatocytesOnline Journal of Public Health Informatics, 2000