Exploring causality via identification of SNPs or haplotypes responsible for a linkage signal
Version of Record online: 16 MAY 2007
© 2007 Wiley-Liss, Inc.
Volume 31, Issue 7, pages 727–740, November 2007
How to Cite
Biernacka, J. M. and Cordell, H. J. (2007), Exploring causality via identification of SNPs or haplotypes responsible for a linkage signal. Genet. Epidemiol., 31: 727–740. doi: 10.1002/gepi.20236
- Issue online: 16 OCT 2007
- Version of Record online: 16 MAY 2007
- Manuscript Accepted: 4 APR 2007
- Manuscript Revised: 22 MAR 2007
- Manuscript Received: 2 FEB 2007
- Wellcome Trust. Grant Number: 074524
- fine mapping;
- conditional tests
In a small chromosomal region, a number of polymorphisms may be both linked to and associated with a disease. Distinguishing the potential causal sites from those indirectly associated due to linkage disequilibrium (LD) with a causal site is an important problem. This problem may be approached by determining which of the associations can explain the observed linkage signal. Recently, several methods have been proposed to aid in the identification of disease associated polymorphisms that may explain an observed linkage signal, using genotype data from affected sib pairs (ASPs) [Li et al.  Am. J. Hum. Genet. 76:934–949; Sun et al.  Am. J. Hum. Genet. 70:399–411]. These methods can be used to test the null hypothesis that a candidate single nucleotide polymorphism (SNP) is the sole causal variant in the region, or is in complete LD with the sole causal variant in the region. We extend variations of these methods to test for complete LD between a disease locus and haplotypes composed of two or more tightly linked candidate SNPs. We study properties of the proposed methods by simulation and apply them to type 1 diabetes data for ASPs and their parents at candidate SNP and microsatellite marker loci in the Insulin (INS) gene region. Genet. Epidemiol. 2007. © 2007 Wiley-Liss, Inc.