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Current understanding of human genetics and genetic analysis of psoriasis
Author(s) -
OKA Akira,
MABUCHI Tomotaka,
OZAWA Akira,
INOKO Hidetoshi
Publication year - 2012
Publication title -
the journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.9
H-Index - 65
eISSN - 1346-8138
pISSN - 0385-2407
DOI - 10.1111/j.1346-8138.2012.01504.x
Subject(s) - psoriasis , genome wide association study , genetics , single nucleotide polymorphism , genetic association , biology , locus (genetics) , missing heritability problem , genetic architecture , heritability , disease , human leukocyte antigen , genetic predisposition , multifactorial inheritance , gene , quantitative trait locus , medicine , immunology , genotype , pathology , antigen
During the past 5 years, genome‐wide association studies (GWAS), primarily based on single nucleotide polymorphism markers, have identified many loci as potential psoriasis susceptibility regions. These studies appeared to provide strong evidence because the susceptibility genes are involved in the interleukin‐23/T‐helper 17 axis of psoriasis immunopathogenesis and/or skin barrier functions. However, the “identified” genes only explained a small proportion of psoriasis heritability, although it is known to be comparatively higher than that of other common diseases. GWAS are based on the hypothesis that disease‐causing variants are high frequency variants within populations. However, this hypothesis is problematic because deleterious variants such as those predisposing to specific diseases will generally not be maintained by selection pressure throughout human evolution. This issue also affects psoriasis studies. Here, we review the current paradigm shift in human genetic analyses and its implications for detection of psoriasis‐causing variants based on linkage analysis and GWAS, except the well‐known psoriasis susceptibility locus HLA‐C .