1. ¹Department of Medical and Molecular Genetics, King's College London School of Medicine at Guy's, King's College and St Thomas' Hospitals, London, UK
2. ²Istituto di Genetica delle Popolazioni-CNR, Alghero, Italy
3. ³Section of Rheumatology, Virginia Mason Medical Center, Seattle, WA, USA
4. ⁴Department of Medicine, Rosalind Russell Medical Research Center for Arthritis, University of California, San Francisco, CA, USA
5. ⁵Oklahoma Medical Research Foundation, Oklahoma City, OK, USA
6. ⁶Department of Medicine, Center for Immunology, University of Minnesota Medical School, Minneapolis, MN, USA
7. ⁷Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden
8. ⁸Division of Rheumatology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
9. ⁹Departments of Human Genetics and Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
10. ¹⁰Oklahoma Medical Research Foundation, University of Oklahoma, Oklahoma City, OK, USA
11. ¹¹US Department of Veterans Affairs Medical Center, Oklahoma City, OK, USA

Correspondence: Professor LA Criswell, Department of Medicine, Division of Rheumatology, University of California, 374 Parnassus Avenue, Box 0500, San Francisco, CA 94143-0500, USA. E-mail: Lindsey.Criswell@ucsf.edu

¹²Current address: NHGRI/NIH, Bethesda, MD, USA.

Received 8 June 2006; Revised 8 August 2006; Accepted 10 August 2006; Published online 14 September 2006.

Abstract

A genetic contribution to the development of systemic lupus erythematosus (SLE) is well established. Several genome-wide linkage scans have identified a number of putative susceptibility loci for SLE, some of which have been replicated in independent samples. This study aimed to identify the regions showing the most consistent evidence for linkage by applying the genome scan meta-analysis (GSMA) method. The study identified two genome-wide suggestive regions on 6p21.1–q15 and 20p11–q13.13 (P-value=0.0056 and P-value=0.0044, respectively) and a region with P-value<0.01 on 16p13–q12.2.

The region on chromosome 6 contains the human leukocyte antigen cluster, and the chromosome 16 and 20 regions have been replicated in several cohorts. The potential importance of the identified genomic regions are also highlighted. These results, in conjunction with data emerging from dense single nucleotide polymorphism typing of specific regions or future genome-wide association studies will help guide efforts to identify the actual predisposing genetic variation contributing to this complex genetic disease.