The International Psoriasis Genetics study: Assessing linkage to 14 candidate susceptibility loci in a cohort of 942 affected sib pairs

M Allen, J W N Barker, A M Bowcock, A D Burden, N Chia, F Capon, E Christophers, M J Daly, J T Elder, C Helms, T Henseler, S Jenisch, A Menter, R Mistry, R P Nair, P E Stuart, D Tillman, R C Trembath, C Veal, J J Voorhees

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Abstract

In an effort to confirm previously reported linkages to psoriasis, we analyzed 942 affected sibling pairs ( ASPs) from 710 pedigrees for 53 polymorphic microsatellites spanning 14 psoriasis candidate regions at an intermarker spacing of similar to5 cM. Maximum LOD score (MLS) analysis of ASPs yielded allele sharing of 60% for markers within the major histocompatibility complex (MHC) (P = 2 x 10(-14)), which yielded a gene-specific lambda(s) of 1.6. Across the remainder of the genome, the strongest evidence of allele sharing was obtained on chromosomes 16q (D16S3032; MLS = 1.3; P = .007) and 10q22 - q23 (D10S2327; MLS = 1.1; P = .012). None of the remaining loci exceeded MLS = 0.9, the value expected to occur by chance once in this study. In agreement with previous studies, strong linkage disequilibrium was also observed between psoriasis and the MHC ( pedigree disequilibrium test P = 3.9 x 10(-8) for D6S1014). Two psoriasis-associated MHC haplotypes were identified with the haplotype-based transmission/ disequilibrium test. Analysis of only those families carrying either of these haplotypes significantly increased the chromosome 16q LOD score from 1.3 to 2.4 (P = .045). These results underscore the importance of theMHCin psoriasis and provide a rationale for more- detailed examination of candidate regions on chromosomes 16q and 10q
Original languageEnglish
Pages (from-to)430 - 437
Number of pages8
JournalAmerican Journal of Human Genetics
Volume73
Issue number2
Publication statusPublished - 1 Aug 2003

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