Meta-Analysis of 23 Type 2 Diabetes Linkage Studies from the International Type 2 Diabetes Linkage Analysis Consortium
Year: 2007
Type: review
Study design: Systematic Review
Abstract: BACKGROUND: The International Type 2 Diabetes Linkage Analysis Consortium was formed to localize type 2 diabetes predisposing variants based on 23 autosomal linkage scans. METHODS: We carried out meta-analysis using the genome scan meta-analysis (GSMA) method which divides the genome into bins of approximately 30 cM, ranks the best linkage results in each bin for each sample, and then sums the ranks across samples. We repeated the meta-analysis using 2 cM bins, and/or replacing bin ranks with measures of linkage evidence: bin maximum LOD score or bin minimum p value for bins with p value <0.05 (truncated p value). We also carried out computer simulations to assess the empirical type I error rates of these meta-analysis methods. RESULTS: Our analyses provided modest evidence for type 2 diabetes-predisposing variants on chromosomes 4, 10, and 14 (using LOD scores or truncated p values), or chromosome 10 and 16 (using ranks). Our simulation results suggested that uneven marker density across studies results in substantial variation in empirical type I error rates for all meta-analysis methods, but that 2 cM bins and scores that make more explicit use of linkage evidence, especially the truncated p values, reduce this problem. CONCLUSION: We identified regions modestly linked with type 2 diabetes by summarizing results from 23 autosomal genome scans.
Source: Human Heredity
DOI: 10.1159/000114164
Institutions: University of Michigan, University of Chicago
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: bronze
Funders: GlaxoSmithKline, Wake Forest University, Helsingin Yliopisto, Helsingin ja Uudenmaan Sairaanhoitopiiri, University of Arkansas for Medical Sciences, Wellcome Trust, Southwest Foundation for Biomedical Research, Diabetes UK, University of Oxford, Lunds Universitet, Hebrew University of Jerusalem, Centre National de la Recherche Scientifique, National Institutes of Health, University of North Carolina at Chapel Hill, University of California, San Francisco, School of Medicine, University of Texas Health Science Center at San Antonio, National Heart, Lung, and Blood Institute, National Institute of Mental Health, National Human Genome Research Institute, Fogarty International Center, National Institute of Diabetes and Digestive and Kidney Diseases, School of Medicine, University of California, San Francisco
Awards: Design and Analysis of Human Gene Mapping Studies, G1540919103, MINORITY INTERNATIONAL RESEARCH TRAINING GRANT, G2048638135, Quantitative Trait Locus Mapping in Human Pedigrees, G220423607, G2511018108, G2895937723, G2988741787, G2998069792, G312666599, G3468304963, CONSORTIUM LINKAGE STUDIES OF TYPE 2 DIABETES, GENETIC EPIDEMIOLOGY OF NIDDM IN MEXICAN AMERICANS, NIDDM Susceptibility Genes in Mexican Americans, G474297630, G4940423171, Genetics of Diabetes in the Amish, G5540814443, G645055089, G6688019574, Understanding the genetic basis of common human diseases: core funding for the Wellcome Trust Centre for Human Genetics., Fine mapping and Positional Cloning of Diabetes Genes, G7531682695, G7852197243, G7997469300, G8950521765, G895200619, G9000054199, G9000104663, G9000108144, Identifying Genes for Type 2 Diabetes: FUSION
OpenAlex ID: W2055433848