1. ¹Department of Epidemiology, University of Texas, MD Anderson Cancer Center, Houston, TX, USA
2. ²Robert S Boas Center for Genomics and Human Genetics, Feinstein Institute for Medical Research, Manhasset, NY, USA
3. ³Department of Laboratory Medicine, University of Washington School of Medicine, Seattle, USA
4. ⁴Genetics and Genomics Branch, NIAMS, NIH, Bethesda, MD, USA
5. ⁵Department of Medicine, Rosalind Russell Medical Research Center for Arthritis, University of California at San Francisco, San Francisco, CA , USA
6. ⁶Rowe Program in Genetics, University of California at Davis, Davis, CA, USA

Correspondence: Dr C Amos, Department of Epidemiology, University of Texas, MD Anderson Cancer Center, 1155 Pressler, Unit 1340, Houston, TX 77030, USA. E-mail: camos@mdanderson.org; PK Gregersen, Feinstein Institute for Medical Research, North Shore LIJ Health System, 350 Community Drive, Manhasset, NY 11030, USA. E-mail: peterg@nshs.edu

Received 8 December 2005; Revised 31 January 2006; Accepted 31 January 2006; Published online 4 May 2006.

Abstract

We have completed a genome wide linkage scan using >5700 informative single-nucleotide polymorphism (SNP) markers (Illumina IV SNP linkage panel) in 642 Caucasian families containing affected sibling pairs with rheumatoid arthritis (RA), ascertained by the North American Rheumatoid Arthritis Consortium. The results show striking new evidence of linkage at chromosomes 2q33 and 11p12 with logarithm of odds (LOD) scores of 3.52 and 3.09, respectively. In addition to a strong and broad linkage interval surrounding the major histocompatibility complex (LOD>16), regions with LOD>2.5 were observed on chromosomes 5 and 10. Additional linkage evidence (LOD scores between 1.46 and 2.35) was also observed on chromosomes 4, 7, 12, 16 and 18. This new evidence for multiple regions of genetic linkage is partly explained by the significantly increased information content of the Illumina IV SNP linkage panel (75.6%) compared with a standard microsatellite linkage panel utilized previously (mean 52.6%). Stratified analyses according to whether or not the sibling pair members showed elevated anticyclic citrullinated peptide titers indicates significant variation in evidence for linkage among strata on chromosomes 4, 5, 6 and 7. Overall, these new linkage data should reinvigorate efforts to utilize positional information to identify susceptibility genes for RA.