This article is part of the supplement: Genetic Analysis Workshop 15: Gene Expression Analysis and Approaches to Detecting Multiple Functional Loci
Mapping a gene for rheumatoid arthritis on chromosome 18q21
Human Genetics Division, University of Southampton, Southampton General Hospital, Tremona Road, Southampton, Hampshire SO16 6YD. UK
BMC Proceedings 2007, 1(Suppl 1):S18 doi:Published: 18 December 2007
Although single chi-square analysis of the North American Rheumatoid Arthritis Consortium (NARAC) data identifies many single-nucleotide polymorphisms (SNPs) with p-values less than 0.05, none remain significant after Bonferroni correction. In contrast, CHROMSCAN evades heavy Bonferroni correction and auto-correlation between SNPs by using composite likelihood to model association across all markers in a region and permutation to assess significance. Analysis by CHROMSCAN identifies a 36-kb interval that includes the most significant SNP (msSNP) observed in a 10-Mb target suggested by linkage. Unexpectedly, stratification by gender and age of onset shows that association evidence comes almost entirely from females with age of onset less than 40. Combining evidence from a meta-analysis of linkage studies and three subsets of the NARAC data provides significant evidence for a determinant of rheumatoid arthritis in a 36-kb interval and illustrates the principle that estimates of location and its information are more powerful than estimates of p-values alone.