Original Paper

Familial Psoriasis and HLA-B: Unambiguous Support for Linkage in 97 Published Families
Richard O. Leder^a, Jonathan N. Mansbridge^b, Joachim Hallmayer^f, Susan E. Hodge<sup>c-e

a</sup> Department of Molecular and Cellular Biology, Psoriasis Research Institute, Palo Alto, Calif.,
^b Advanced Tissue Sciences, La Jolla, Calif.,
^c Department of Psychiatry, Columbia University, College of Physicians and Surgeons,
^d Division of Biostatistics, School of Public Health, Columbia University, and
^e Division of Clinical-Genetic Epidemiology, New York State Psychiatric Institute, New York, N.Y., USA;
^f Department of Psychiatry, University of Western Australia, Perth, Australia

Address of Corresponding Author

Hum Hered 1998;48:198-211 (DOI: 10.1159/000022802)

  Key Words

• Psoriasis
• Genetic linkage
• HLA-B
• HLA association
• Linkage disequilibrium
• Identity by descent
• Two-locus models
• Heterogeneity

  Abstract

The existence of a psoriasis susceptibility locus, PSORS1 (HUGO/GDB-approved symbol), in or near the HLA region of chromosome 6 is strongly supported by a lod score analysis of HLA-B and psoriasis in 97 families from 16 published datasets. Families included in the dataset represent all the psoriasis families with usable HLA data that we could find in the published literature through May 1997. The recombination fraction between PSORS1 and HLA-B is estimated to be at or near 0.00, with a maximum two-point lod score of 23.7, assuming a dominant mode of inheritance with low (20%) penetrance at the PSORS1 locus. Although these families are geographically and ethnically diverse, there is no evidence for linkage heterogeneity at the HLA-linked locus in this analysis. We also conclude that the HLA-B17 allele, which is strongly associated with psoriasis, is unlikely itself to contribute directly to psoriasis susceptibility; rather, the HLA-B locus is probably tightly linked to the PSORS1 locus. Finally, we raise the possibility of a two-locus/heterogeneity model as one way to reconcile several findings in the literature.

  Author Contacts

Dr. Susan E. Hodge
NYSPI, Unit 14, 722 West 168th Street
New York, NY 10032 (USA)
Tel. +1 (212) 543 5606, Fax +1 (212) 568 3534
E-Mail seh2@columbia.edu

  Article Information

Received: Received: July 29, 1997
Revision received: March 3, 1998
Accepted: March 9, 1998
Number of Print Pages : 14
Number of Figures : 1, Number of Tables : 3, Number of References : 64