Molecular dissection of psoriasis: integrating genetics and biology.
Psoriasis is a common and debilitating disease of the skin, nails, and joints, with an acknowledged but complex genetic basis. Early genome-wide linkage studies of psoriasis focused on segregation of microsatellite markers in families; however, the only locus consistently identified resided in the major histocompatibility complex. Subsequently, several groups mapped this locus to the vicinity of HLA-C, and two groups have reported HLA-Cw6 itself to be the major susceptibility allele. More recently, the development of millions of single-nucleotide polymorphisms, coupled with the development of high-throughput genotyping platforms and a comprehensive map of human haplotypes, has made possible a genome-wide association approach using cases and controls rather than families. Taking advantage of these developments, we participated in a collaborative genome-wide association study of psoriasis involving thousands of cases and controls. Initial analysis of these data revealed and/or confirmed association between psoriasis and seven genetic loci-HLA-C, IL12B, IL23R, IL23A, IL4/IL13, TNFAIP3, and TNIP1-and ongoing studies are revealing additional loci. Here, we review the epidemiology, immunopathology, and genetics of psoriasis, and present a disease model integrating its genetics and immunology.
Elder
James T
JT
Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan, USA. jelder@umich.edu
Bruce
Allen T
AT
Gudjonsson
Johann E
JE
Johnston
Andrew
A
Stuart
Philip E
PE
Tejasvi
Trilokraj
T
Voorhees
John J
JJ
Abecasis
Gonçalo R
GR
Nair
Rajan P
RP
D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D011565:Psoriasis / Q000453:epidemiology / Q000235:genetics / Q000276:immunology
D005819:Genetic Markers