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.

Theeuwes M, Leder RO: Hereditary insights in psoriasis. Eur J Dermatol 1993;3:335–341.
Elder JT, Nair RP, Guo S-W, Henseler T, Christophers E, Voorhees JJ: The genetics of psoriasis. Arch Dermatol 1994;130:216–224.
Trembath RC, Clough RL, Rosbotham JL, Jones AB, Camp RDR, Frodsham A, Browne J, Barber R, Terwilliger J, Lathrop GM, Barker JNWN: Identification of a major susceptibility locus on chromosome 6p and evidence for further disease loci revealed by a two stage genome-wide search in psoriasis. Hum Mol Genet 1997;6:813–820.
Russell TJ, Schultes LM, Kuban DJ: Histocompatibility (HL-A) antigens associated with psoriasis. N Engl J Med 1972;287:738–739.
White SH, Newcomer VD, Mickey MR, Terasaki PI: Disturbance of HL-A antigen frequency in psoriasis. N Engl J Med 1972;287:740–743.
Tiwari JL, Terasaki PI: HLA and Disease Associations. New York, Springer, 1985.
Tomfohrde J, Silverman A, Barnes R, Fernandez-Vina MA, Young M, Lory D, Morris L, et al: Gene for familial psoriasis susceptibility mapped to the distal end of human chromosome 17q. Science 1994;264:1141–1145.
Kirkpatrick H, Barnes R, Young M, Kuykendahl L, Menter A, Bowcock A: Progress in the search for the psoriasis susceptibility gene at 17qter. Am J Hum Genet 1995;57:A188.
Nair RP, Guo S, Jenisch S, Henseler T, Lange EM, Terhune M, Westphal E, Christophers E, Voorhees JJ, Elder JT: Scanning chromosome 17 for psoriasis susceptibility: Lack of evidence for a distal 17q locus. Hum Hered 1995;45:219–223.
Matthews D, Fry L, Powles A, Weissenbach J, Williamson R: Confirmation of genetic heterogeneity in familial psoriasis. J Med Genet 1995;32:546–548.
Matthews D, Fry L, Powles A, Weber J, McCarthy M, Fisher E, Davies K, Williamson R: Evidence that a locus for familial psoriasis maps to chromosome 4q. Nature Genet 1996;14:231–233.
Nair RP, Henseler T, Jenisch S, Stuart P, Bichakjian CK, Lenk W, Westphal E, Guo SW, Christophers E, Voorhees JJ, Elder JT: Evidence for two psoriasis susceptibility loci (HLA and 17q) and two novel candidate regions (16q and 20p) by genome-wide scan. Hum Mol Genet 1997;6:1349–1356.
Chang JCC, Smith LR, Froning KJ, Schwabe BJ, Laxer JA, Caralli LL, Kurland HH, et al: CD8+ T cells in psoriatic lesions preferentially use T-cell receptor Vβ3 and/or Vβ13.1 genes. Proc Natl Acad Sci USA 1994;91:9282–9286.
Civatte J, Laxarovici C, Ganas P, Leon S, Hors J, Contu L, Dausset J: Le système HL-A dans le psoriasis. Étude de 31 families. Ann Dermatol Venereol 1997;104:525–532.
Suarez-Almazor ME, Russell AS: The genetics of psoriasis: Haplotype sharing in siblings with the disease. Arch Dermatol 1990;126:1040–1042.
Leder RO, Farber EM, Mansbridge J, Hallmayer J: Genetic mapping of the psoriasis susceptibility locus: Retrospective analysis of 84 kindreds shows linkage to polymorphic class 1 HLA loci. J Invest Dermatol 1994;102:530.
Hawkins BR, Tiwari JL, Lowe N, Wolfish P, Pollock CA, Cho YW, Terasaki PI: HLA and psoriasis; in Terasaki PI (ed): Histocompatibility Testing 1980: Report on the 8th International Histocompatibility Workshop. Los Angeles, UCLA Tissue Typing Laboratory, 1980, pp 711–714.
Lin JD, Auerbach AD, Auerbach R, Allen RG, Mann WR, Olsen DA, Gottlieb AB, Carter DM: Genetic linkage studies in psoriasis. J Invest Dermatol 1991;96:535s.
Nair RP, Henseler T, Lunetta K, Guo SW, Terhune M, Westphal E, Christophers E, et al: Exclusion of tight linkage between familial psoriasis and HLA genes under a single gene, autosomal dominant model. J Invest Dermatol 1993;100:539.
Christophers E, Kreuger GG: Psoriasis; in Fitzpatrick TB, et al (eds): Dermatology in General Medicine. New York, McGraw-Hill, 1991, pp 461–491.
Marcusson JA, Moller E, Thyresson N: Penetration of HLA-linked psoriasis-predisposing gene(s): A family investigation. Acta Derm Venereol 1976;56:453–463.
Lathrop GM, Lalouel JM, Julier C, Ott J: Strategies for multilocus linkage analysis in humans. Proc Natl Acad Sci USA 1984;81:3443–3446.
Terwilliger JD, Ott J: Handbook of Human Genetic Linkage. Baltimore, Johns Hopkins, 1994.
Greenberg DA: Inferring mode of inheritance by comparison of lod scores. Am J Med Genet 1989;34:480–486.
USDHHS: Vital and Health Statistics, Current Estimates from the National Health Interview Survey, 1990, series 10: Data from the National Health Survey, No 181. Washington, US Government Printing Office, 1991, Publ No PHS92–1509.
Durner M, Greenberg DA, Hodge SE: Phenocopies vs. genetic heterogeneity: Can we use phenocopy frequencies in linkage analysis to compensate for heterogeneity? Hum Hered 1996;46:265–273.
Ott J: Analysis of Human Genetic Linkage. Baltimore, Johns Hopkins, 1991.
Lokki M, Julin M: HLA-A,B,C gene and haplotype frequencies in the Finnish population. Tissue Antigens 1982;20:239–250.
Imanishi T, Akaza T, Kimura A, Tokunaga K, Gojobori T: Allele and haplotype frequencies for HLA and complement loci in various ethnic groups; in Tsuji K, Aizawa M, Sasazuki T (eds): HLA 1991: Proceedings of the 11th International Histocompatibility Workshop and Conference. New York, Oxford University Press, 1992, vol 1, pp 1065–1220.
Bodmer JG, Marsh SGE, Albert ED, Bodmer WF, Dupont B, Erlich H, Mach B, et al: Nomenclature for factors of the HLA system, 1991; in Tsuji K, Aizawa M, Sasazuki T (eds): HLA 1991: Proceedings of the 11th International Histocompatibility Workshop and Conference. New York, Oxford University Press, 1992, vol 1, pp 17–31.
Ott J: A simple scheme for the analysis of HLA linkages in pedigrees. Ann Hum Genet 1978;42:255–257.
Chieregato GC, Bezze G, Valenti GC, Pasini C, Fagiolo U: Studie degli antigeni HLA in nuclei familiari psoriasici. G Ital Dermatol Venereol 1982;117:63–66.
Hodge SE, Anderson CE, Neiswanger K, Sparkes RS, Rimoin DL: The search for heterogeneity in insulin-dependent diabetes mellitus (IDDM): Linkage studies, two-locus models, and genetic heterogeneity. Am J Hum Genet 1983;35:1139–1155.
Morton NE: The detection and estimation of linkage between the genes for elliptocytosis and the Rh blood type. Am J Hum Genet 1956;8:80–96.
Edwards AWF: Likelihood. Baltimore, Johns Hopkins, 1992.
Smith CAB: Testing for heterogeneity of recombination fraction values in human genetics. Am Hum Genet 1963;27:175–182.
Ott J: Counting methods (EM algorithm) in human pedigree analysis: Linkage and segregation analysis. Ann Hum Genet 1977;40:443–454.
Risch N, Baron M: X-linkage and heterogeneity in bipolar-related major affective illness: Reanalysis of linkage data. Ann Hum Genet 1982;46:153–166.
Clerget-Darpoux F: Bias of the estimated recombination fraction and lod score due to an association between a disease gene and a marker gene. Ann Hum Genet 1982;46:363–372.
Karvonen J, Tiilikainen A, Lassus A: HLA antigens in psoriasis. A family study. Ann Clin Res 1976;8:298–304.
Woodrow JC, Dave VK, Usher N, Anderson J: The HL-A system and psoriasis. Br J Dermatol 1975;92:427–436.
Gunn I, Leheny W, Lakshmipathi T, Lament MA, Faed M: HLA antigens in a Scottish psoriatic population. Tissue Antigens 1979;14:157–164.
Laurentaci G, Lomuto M, Favoino B: Immunogenetic analysis of association between HLA antigens and psoriasis vulgaris: Population and family studies. Dermatologica 1982;165:591–600.
Hodge SE, Abreu PC, Greenberg DA: Magnitude of type I error when single-locus linkage analysis is maximized over models: A simulation study. Am J Hum Genet 1997;60:217–227.
Spence MA, Sparkes RS, Heckenlively J, Pearlman J, Zedalis D, Sparkes M, Crist M, Tideman S: Probable genetic linkage between autosomal dominant retinitis pigmentosa (RP) and amylase (Amy-2): Evidence that an RP locus is on chromosome No. 1. Am J Hum Genet 1977;29:397–404.
Spence MA, Sparkes RS, Heckenlively J, Pearlman J, Zedalis D, Sparkes M, Crist M, Tideman S: Erratum. Am J Hum Genet 1977;29:592.
Ott J: Strategies for characterizing highly polymorphic markers in human gene mapping. Am J Hum Genet 1992;51:283–290.
Greenberg DA, Hodge SE, Vieland VJ, Spence MA: Affected-only linkage methods are not a panacea. Am J Hum Genet 1996;58:892–895.
Clerget-Darpoux F, Bonaïti-Pellié C, Hochez J: Effects of misspecifying genetic parameters in lod score analysis. Biometrics 1986;42:393–399.
Elston RC: Man bites dog? The validity of maximizing lod scores to determine mode of inheritance. Am J Med Genet 1989;34:487–488.
MacLean CJ, Bishop DT, Sherman SL, Diehl SR: Distribution of lod scores under uncertain mode of inheritance. Am J Hum Genet 1993;52:354–361.
Hodge SE, Elston RC: Lods, wrods, and mods: The interpretation of lod scores calculated under different models. Genet Epidemiol 1994;11:329–342.
Greenberg DA, Berger B: Using lod-score differences to determine mode of inheritance: A simple robust method even in the presence of heterogeneity and reduced penetrance. Am J Hum Genet 1994;55:834–840.
Greenberg DA: Linkage analysis of ‘necessary’ disease loci versus ‘susceptibility’ loci. Am J Hum Genet 1993;52:135–143.
Hodge SE: Linkage analysis versus association analysis: Distinguishing between two models that explain disease-marker associations. Am J Hum Genet 1993;53:367–384.
Pietrzyk JJ, Turowski G, Kapinska-Mrowka M, Rozanski B: Family studies in psoriasis. Part I. Arch Dermatol Res 1982;273:287–294.
Pietrzyk JJ, Turowski G, Kapinska-Mrowka M: Family studies in psoriasis. II. Inheritance of HLA genotypes. Arch Dermatol Res 1982;273:295–300.
Espinoza LR, Bombardier C, Gaylord SW, Lauter S, Vasey FB, Osterland CK: Histocompatibility studies in psoriasis vulgaris: Family studies. J Rheumatol 1980;7:445–452.
Cao K, Song F, Li H, Xu S, Liu Z, Su X, Wang F: Association between HLA antigens and families with psoriasis vulgaris. Chin Med J 1993;106:132–135.
Sun Y, An J, Li S, Li H, Chen W, Lin L, Xu L, et al: HLA antigen distribution and haplotype segregation in Chinese patients with psoriasis. Chin Med J 1987;200:236–241.
Turowski G, Pietrzyk J, Turowska B, Kapinska-Mrowka M: Immunogenetic aspects of psoriasis in the light of population and family studies. Acta Med Pol 1980;21:269–276.
Marcusson JA, Moiler E, Rosenthal L, Lindwall N, Thyresson N: Psoriasis and arthritic lesions in relation to the inheritance of HLA genotypes: A family study. Acta Derm Venereol 1978;58:511–519.
Marcusson JA, Strom H, Lindvall N: Psoriasis, peripheral arthritis, sacroiliitis and juvenile chronic arthritis: A family study in relation to segregation of HLA antigens. J Rheumatol 1983;10:619–623.
Krulig L, Farber EM, Grumet FC, Payne RO: Histocompatibility (HL-A) antigens in psoriasis. Arch Dermatol 1975;111:857–860.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.