A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance
Top Cited Papers
- 13 May 2012
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Genetics
- Vol. 44 (6), 659-669
- https://doi.org/10.1038/ng.2274
Abstract
Claudia Langenberg, James Meigs and colleagues apply a joint meta-analysis approach that accounts for differences in body mass index to identify variants associated with glycemic traits. They report six new loci associated with fasting insulin levels and provide insights into the genetic basis of insulin resistance. Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and β-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci associated with fasting insulin at P < 5 × 10−8 in combined discovery and follow-up analyses of 52 studies comprising up to 96,496 non-diabetic individuals. Risk variants were associated with higher triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci in insulin resistance pathways. The discovery of these loci will aid further characterization of the role of insulin resistance in T2D pathophysiology.Keywords
This publication has 83 references indexed in Scilit:
- Insulin resistance influences the association of adiponectin levels with diabetes incidence in two population-based cohorts: the Cooperative Health Research in the Region of Augsburg (KORA) S4/F4 study and the Framingham Offspring StudyDiabetologia, 2011
- Meta-analysis of gene-environment interaction: joint estimation of SNP and SNP × environment regression coefficientsGenetic Epidemiology, 2010
- MaCH: using sequence and genotype data to estimate haplotypes and unobserved genotypesGenetic Epidemiology, 2010
- Impact of repeated measures and sample selection on genome‐wide association studies of fasting glucoseGenetic Epidemiology, 2010
- Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controlsNature, 2010
- A Weighted False Discovery Rate Control Procedure Reveals Alleles at FOXA2 that Influence Fasting Glucose LevelsAmerican Journal of Human Genetics, 2010
- Heritability of insulin sensitivity and lipid profile depend on BMI: evidence for gene–obesity interactionDiabetologia, 2009
- A new multipoint method for genome-wide association studies by imputation of genotypesNature Genetics, 2007
- Joint analysis is more efficient than replication-based analysis for two-stage genome-wide association studiesNature Genetics, 2006
- Quantifying heterogeneity in a meta-analysisStatistics in Medicine, 2002