Genetics of psoriasis in Iceland: evidence for linkage of subphenotypes to distinct Loci.
Psoriasis is a chronic inflammatory skin disease with overlapping subphenotypes. It has a strong complex genetic component, but has been problematic to identifying significant loci. We evaluated 1000 patients with chronic plaque psoriasis and documented several subphenotypes. Here we report results of genome-wide linkage scans for psoriasis genes in 238 Icelandic families with 874 patients. MHC linkage was confirmed with LOD score of 10.9. When the entire cohort was analyzed, two other loci with LOD scores of 2.5 and 1.5 were observed on 16q and 4q, respectively. Stratification into subphenotypes revealed additional loci with LOD scores exceeding or approaching significance. A LOD score of 5.7 appeared on 16q in PsA patients with analysis conditioned on parental inheritance. A LOD score of 3.6 on 4q was detected when disease occurred at or older than 17 y, our median cohort age. This locus was defined by a marker near one reportedly displaying significant linkage in a Chinese psoriasis population and near suggestive linkage in a Caucasian population. A LOD of 3.0 was observed on 10q when disease onset occurred in the scalp. Furthermore, clinical stratification either revealed or increased LOD scores when compared to unstratified analysis and some coincided with previous reports.
Karason
Ari
A
deCODE Genetics, Reykjavik, Iceland. ari@decode.is
Gudjonsson
Johann E
JE
Jónsson
Hjörtur H
HH
Hauksson
Valdimar B
VB
Runarsdottir
E Hjaltey
EH
Stefansson
Kari
K
Valdimarsson
Helgi
H
Gulcher
Jeffrey R
JR
D017668:Age of Onset; D015535:Arthritis, Psoriatic / Q000235:genetics; D002874:Chromosome Mapping; D002885:Chromosomes, Human, Pair 16; D002894:Chromosomes, Human, Pair 4; D015331:Cohort Studies; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D007055:Iceland; D008126:Lod Score; D008285:Major Histocompatibility Complex / Q000235:genetics; D009262:Nails / Q000473:pathology; D010641:Phenotype; D011565:Psoriasis / Q000453:epidemiology / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D012536:Scalp Dermatoses / Q000453:epidemiology; D012867:Skin / Q000293:injuries; D014947:Wounds and Injuries / Q000150:complications