Psoriasis is a chronic, immune-mediated disorder with a strong genetic basis, albeit polygenic in nature

Heritability of psoriasis

• Twin studies: Twin studies have shown greater concordance rates for psoriasis in monozygotic (MZ) twins than in dizygotic (DZ) twins, with heritability estimates between 66% and 90%
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  Heritability of psoriasis in a large twin sample

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  . This supports a genetic influence on psoriasis, but also highlights the fact that genes are not the only explanation for the disease.
• Familial aggregation: The recurrence risk ratio for both psoriatic arthritis (PsA) and psoriasis is high in first-degree relatives (FDRs) and siblings of patients with PsA, confirming a strong heritable component
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  Familial aggregation of psoriatic arthritis

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Genetic basis of psoriasis

• Major histocompatibility complex (MHC): Approximately half of the accountable genetic effect of psoriasis maps to the major histocompatibility complex
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  Psoriasis

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• Other loci: More than 70 other loci have been identified, many of which implicate nuclear factor-κB, interferon signalling, and the IL-23-IL-23 receptor axis
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  Psoriasis

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• Epistatic interactions: Recent studies have shown epistatic interactions involving HLA-C*06, ERAP1, and LCE3C_LCE3B-del, which makes psoriasis a unique model to investigate genetic and biological interactions of associated genes in a complex disease
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  Genetics of psoriasis: evidence for epistatic interaction between skin barrier abnormalities and immune deviation

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• Shared genetic factors: Shared genetic factors may contribute to the etiology of both psoriasis and other skin or immune-mediated disorders
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  An association study of 22 candidate genes in psoriasis families reveals shared genetic factors with other autoimmune and skin disorders

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Genome-wide studies

• Genome-wide association studies (GWAS): GWAS have identified more than 60 psoriasis-susceptibility loci, but genes are estimated to explain only one-third of the heritability in psoriasis, suggesting additional, yet unidentified, sources of heritability
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  Genome-wide DNA methylation profiling identifies differential methylation in uninvolved psoriatic epidermis

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• Pathway analysis: Genome-wide pathway analysis has identified genetic pathways associated with psoriasis risk, including retinol metabolism, transport of inorganic ions and amino acids, and post-translational protein modification
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  Genome-wide pathway analysis identifies genetic pathways associated with psoriasis

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In conclusion, psoriasis is a complex multifactorial disease with a strong heritable component. Its genetic basis is polygenic, involving multiple loci and pathways, and shared genetic factors may contribute to its etiology along with other skin or immune-mediated disorders.