1. The International Psoriasis Genetics Study: Assessing Linkage to 14 Candidate Susceptibility Loci in a Cohort of 942 Affected Sib Pairs
- Author
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R Mistry, Stefan Jenisch, Jwn Barker, James T. Elder, Colin Veal, Alan Menter, Nicholas V.C. Chia, Mark J. Daly, A D Burden, Enno Christophers, Philip E. Stuart, Tilo Henseler, D Tillman, Cynthia Helms, Francesca Capon, Rajan P. Nair, John J. Voorhees, M Allen, Anne M. Bowcock, and Richard C. Trembath more...
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Male ,Genetic Linkage ,chemical and pharmacologic phenomena ,Biology ,Cohort Studies ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Report ,Psoriasis ,Databases, Genetic ,Genetics ,medicine ,Humans ,Genetics (clinical) ,030304 developmental biology ,Linkage (software) ,0303 health sciences ,Polymorphism, Genetic ,Chromosomes, Human, Pair 10 ,medicine.disease ,Sib pairs ,Pedigree ,Cohort ,Susceptibility locus ,Female ,Chromosomes, Human, Pair 16 ,Microsatellite Repeats - 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 approximately 5 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 the MHC in psoriasis and provide a rationale for more-detailed examination of candidate regions on chromosomes 16q and 10q. more...
- Published
- 2003
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