Work

Identifying Plausible Genetic Models Based on Association and Linkage Results: Application to Type 2 Diabetes

Year: 2012

Type: article

Abstract: When planning resequencing studies for complex diseases, previous association and linkage studies can constrain the range of plausible genetic models for a given locus. Here, we explore the combinations of causal risk allele frequency (RAFC ) and genotype relative risk (GRRC ) consistent with no or limited evidence for affected sibling pair (ASP) linkage and strong evidence for case-control association. We find that significant evidence for case-control association combined with no or moderate evidence for ASP linkage can define a lower bound for the plausible RAFC . Using data from large type 2 diabetes (T2D) linkage and genome-wide association study meta-analyses, we find that under reasonable model assumptions, 23 of 36 autosomal T2D risk loci are unlikely to be due to causal variants with combined RAFC < 0.005, and four of the 23 are unlikely to be due to causal variants with combined RAFC < 0.05.

Source: Genetic Epidemiology

DOI: 10.1002/gepi.21668

Authors: Weihua Guan, Michael Boehnke, Anna Pluzhnikov, Nancy J. Cox, Laura J. Scott

Institutions: University of Minnesota, University of Michigan, University of Chicago

Language: English

Topic: Genetic Associations and Epidemiology

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: bronze

Funders: National Institutes of Health, National Human Genome Research Institute, National Institute of Diabetes and Digestive and Kidney Diseases