The Genetics of Psoriasis and Psoriatic Arthritis

Genetic epidemiological studies have demonstrated a significant genetic basis to both psoriasis and psoriatic arthritis (PsA). Although candidate gene association studies had identified genes for disease susceptibility, recent genome-wide association studies have demonstrated robust associations both within and outside the major histocompatibility region on chromosome 6p. The susceptibility genes identified include HLA-C, IL13, IL4, TNFAIP3, IL23A, IL23R, IL28RA, REL, IFIH1, ERAP, TRAF3IP2, NFKBIA, TYK2, ZNF313, NOS2, FBXL19 and NFKBIA in subjects of European ethnicity and HLA-C, IL12B, LCE3D, ERAP1, TNIP1, PTTG1, CSMD1, GJB2, SERPINB8 and ZNF816A in subjects of Chinese ethnicity. These associations provide us with a model for the pathogenesis of psoriasis involving skin barrier function, innate and adaptive immunity. Gene–gene and gene–environmental interaction effects have also been demonstrated. However, loci identified to date do not fully account for the high heritability of psoriasis and PsA, and therefore many genetic as well as environmental factors and interaction effects remain to be determined. This article reviews the current status of genetic studies in psoriasis and PsA.