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Linkage analysis of SLE susceptibility: confirmation of SLER1 at 5p15.3

Genes & Immunity volume 5, pages 209–214 (2004)Cite this article

Abstract

We detected a novel susceptibility gene, SLER1, for systemic lupus erythematosus (SLE) at 5p15.3.1 This finding was based on a selected subgroup of SLE families, where two or more family members have had alleged rheumatoid arthritis (SLE-RA). The main objective of this study was to replicate the linkage at 5p15.3 based on an independent data set of 88 SLE-RA families. Heterogeneity in the genetic model led us to use a nonparametric allele-sharing method. Since our a priori hypothesis of linkage at 5p15.3 was fixed, we genotyped six markers at the linked region. Our new results replicate the initial linkage at 5p15.3 (Zlr=2.58, P<0.005, LOD=1.45). Moreover, evidence of linkage was sustained when analysis was restricted to the subset of SLE families who had 3 or more individuals with alleged RA (Zlr=3.32, P=0.008, LOD=2.40) The results of our previous findings, together with these new results, confirm the SLER1 linkage at 5p15.3. Our results also demonstrate the utility of clinically defined subgroup analysis for detecting susceptibility loci for complex genetic diseases, such as SLE.

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Acknowledgements

We thank the participating patients and family members, as well as their referring physicians. We also acknowledge the helpful comments and suggestions from three referees. Some of the 88 pedigrees were obtained from the Lupus Multiplex Registry and Repository (AR12253). The study was supported by the NIH (AR048928, AR42460, AI24717, AR048940, AR049084, AR15577, and AI31584) the US Department of Veterans Affairs.

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Authors and Affiliations

  1. Arthritis and Immunology Research Program, Oklahoma City, OK, USA

    SK Nath, B Namjou, CP Garriott, S Frank, J Kilpatrick, JA Kelly & JB Harley

  2. Genetic Epidemiology Unit, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA

    SK Nath, JA Kelly & JB Harley

  3. Cardiology Clinic of Muskogee, Muskogee, OK, USA

    PA Joslin

  4. Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA

    JB Harley

  5. US Department of Veterans Affairs Medical Center, Oklahoma City, OK, USA

    JB Harley

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  1. SK Nath
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  2. B Namjou
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  7. JA Kelly
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Correspondence to SK Nath.

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Nath, S., Namjou, B., Garriott, C. et al. Linkage analysis of SLE susceptibility: confirmation of SLER1 at 5p15.3. Genes Immun 5, 209–214 (2004). https://doi.org/10.1038/sj.gene.6364060

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  • DOI: https://doi.org/10.1038/sj.gene.6364060

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