Systemic lupus erythematosus genome scan: support for linkage at 1q23, 2q33, 16q12-13, and 17q21-23 and novel evidence at 3p24, 10q23-24, 13q32, and 18q22-23

Abstract

Objective: To identify chromosome regions likely to harbor genes that predispose to the development of systemic lupus erythematosus (SLE) by analyzing a full genome scan in nuclear families ascertained for siblings with SLE.

Methods: Approximately 400 multiallelic markers spaced an average of 10 cM apart were genotyped in a multiethnic panel of 238 individuals from 62 multiplex SLE families having 88 affected sibling pairs and 456 total sibling pairs. Findings were analyzed by 2 model-free statistical linkage procedures.

Results: Evidence supporting linkage to 4 previously reported (1q23, 2q33, 16q12-13, and 17q21-23) and 4 novel (3p24, 10q23-24, 13q32, and 18q22-23) chromosome regions was revealed. Stratification by family ethnicity indicated that linkage to 3 regions, 2q33, 10q23-24, and 18q22-23, was derived primarily from the Caucasian families, while linkage to 17q21-23 was seen primarily in the non-Caucasian families.

Conclusion: Linkage to the same chromosome regions in independent cohorts is a critical step in finding the genes that predispose to a complex disorder such as SLE. Four linked regions also seen in independent SLE cohorts lend credibility to the 4 novel regions identified by these analyses. Substantial linkage information was gleaned by genotyping and analyzing the unaffected siblings. These results provide additional evidence that the SLE clinical phenotype is genetically complex, multigenic, and heterogeneous.