The International Psoriasis Genetics Study: assessing linkage to 14 candidate susceptibility loci in a cohort of 942 affected sib pairs - PubMed (original) (raw)

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

International Psoriasis Genetics Consortium. Am J Hum Genet. 2003 Aug.

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.

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Electronic-Database Information

    1. Daly Lab at the Whitehead Institute, http://www-genome.wi.mit.edu/personal/mjdaly/ (for characterization of patterns of mammalian genetic variation)
    1. Online Mendelian Inheritance in Man (OMIM), http://www.ncbi.nlm.nih.gov/Omim/ (for psoriasis susceptibility)

References

    1. Balendran N, Clough RL, Arguello JR, Barber R, Veal C, Jones AB, Rosbotham JL, Little AM, Madrigal A, Barker JN, Powis SH, Trembath RC (1999) Characterization of the major susceptibility region for psoriasis at chromosome 6p21.3. J Invest Dermatol 113:322–328 - PubMed
    1. Barker JN (1998) Pathogenesis of psoriasis. J Dermatol 25:778–781 - PubMed
    1. Becker KG, Simon RM, Bailey-Wilson JE, Freidlin B, Biddison WE, McFarland HF, Trent JM (1998) Clustering of non-major histocompatibility complex susceptibility candidate loci in human autoimmune diseases. Proc Natl Acad Sci USA 95:9979–9984 - PMC - PubMed
    1. Bhalerao J, Bowcock AM (1998) The genetics of psoriasis: a complex disorder of the skin and immune system. Hum Mol Genet 7:1537–1545 - PubMed
    1. Borgiani P, Vallo L, D'Apice MR, Giardina E, Pucci S, Capon F, Nistic S, Chimenti S, Pallone F, Novelli G (2002) Exclusion of CARD15/NOD2 as a candidate susceptibility gene to psoriasis in the Italian population. Eur J Dermatol 12:540–542 - PubMed

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