Integrating Genetic Association, Genetics of Gene Expression, and Single Nucleotide Polymorphism Set Analysis to Identify Susceptibility Loci for Type 2 Diabetes Mellitus
Year: 2012
Type: article
Abstract: Large-scale genome-wide association studies (GWAS) have identified over 40 genomic regions significantly associated with type 2 diabetes mellitus. However, GWAS results are not always straightforward to interpret, and linking these loci to meaningful disease etiology is often difficult without extensive follow-up studies. The authors expanded on previously reported type 2 diabetes mellitus GWAS from the nested case-control studies of 2 prospective US cohorts by incorporating expression single nucleotide polymorphism (SNP) information and applying SNP set enrichment analysis to identify sets of SNPs associated with genes that could provide further biologic insight to traditional genome-wide analysis. Using data collected between 1989 and 1994 in these previous studies to form a nested case-control study, the authors found that 3 of the most significantly associated SNPs to type 2 diabetes mellitus in their study are expression SNPs to the lymphocyte antigen 75 gene (LY75), the ubiquitin-specific peptidase 36 gene (USP36), and the phosphatidylinositol transfer protein, cytoplasmic 1 gene (PITPNC1). SNP set enrichment analysis of the GWAS results identified enrichment for expression SNPs to the macrophage-enriched module and the Gene Ontology (GO) biologic process fat cell differentiation human, which includes the transcription factor 7-like 2 gene (TCF7L2), as well as other type 2 diabetes mellitus-associated genes. Integrating genome-wide association, gene expression, and gene set analysis may provide valuable biologic support for potential type 2 diabetes mellitus susceptibility loci and may be useful in identifying new targets or pathways of interest for the treatment and prevention of type 2 diabetes mellitus.
Source: American Journal of Epidemiology
DOI: 10.1093/aje/kws123
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: bronze
Awards: GWAS of Venous Thrombosis, G1271251741, G1338396984, G1798569254, G1848479244, G1955273565, G214012886, G2313542652, G2548880556, Study of Addiction: Genetics and Environment, International Consortium to Identify Genes and Interactions Controlling Oral Clef, Genes and Environment Initiatives in Type 2 Diabetes, G2851966638, GENETIC SUSCEPTIBILITY TO CANCER IN MULTIETHNIC COHORTS, Genome-wide association studies of prematurity and its complications, GWA for Gene-Environment Interaction Effects Influencing CHD, G3799582765, Dental Caries: Whole Genome Association and Gene x Environment Studies, Genes and Environment Initiative in Glaucoma, GWA Mapping: Maternal Metabolism-Birth Weight Interactions, G4562300860, Genome Wide Association Coordinating Center, GWAS of longitudinal blood pressure profiles from young adulthood to middle-age, G5654214539, JH/CIDR Genotyping for Genome-Wide Association Studies, Genetic Risk to Stroke in Smokers and Nonsmokers in Two Ethnic Groups, FAMILY STUDY OF COCAINE DEPENDENCE, G693077865, G7697152668, G8267674335, G858805679, Collaborative Study on the Genetics of Alcoholism (COGA)., Genome-Wide Association Studies
OpenAlex ID: W2122003173