Contract grant sponsor: National Institutes of Health; Contract grant numbers: HG000376; DK062370.
Identifying Plausible Genetic Models Based on Association and Linkage Results: Application to Type 2 Diabetes
Article first published online: 3 AUG 2012
© 2012 Wiley Periodicals, Inc.
Volume 36, Issue 8, pages 820–828, December 2012
How to Cite
Guan, W., Boehnke, M., Pluzhnikov, A., Cox, N. J. and Scott, L. J. (2012), Identifying Plausible Genetic Models Based on Association and Linkage Results: Application to Type 2 Diabetes. Genet. Epidemiol., 36: 820–828. doi: 10.1002/gepi.21668
- Issue published online: 14 NOV 2012
- Article first published online: 3 AUG 2012
- Manuscript Accepted: 20 JUN 2012
- Manuscript Revised: 19 JUN 2012
- Manuscript Received: 24 JAN 2012
- National Institutes of Health. Grant Numbers: HG000376, DK062370
- gene mapping;
- genetic structure;
- complex diseases
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.