Three novel structural variations at the major histocompatibility complex and IL12B predispose to psoriasis

Area of Science:

• Genomics
• Human Genetics
• Dermatology

Background:

• Structural variations (SVs), DNA alterations of ≥ 50 base pairs, are implicated in complex human diseases.
• A comprehensive genome-wide investigation for SVs predisposing to psoriasis was previously lacking.

Purpose of the Study:

• To investigate the association between structural variations (SVs) and psoriasis.
• To identify novel genetic variants contributing to psoriasis susceptibility.

Main Methods:

• Genome-wide screening of SVs using imputation across five independent Han Chinese cohorts (45,386 participants).
• Fine-mapping, genetic interaction, and RNA expression analyses were employed to elucidate SV mechanisms.
• Analysis included single-nucleotide polymorphisms (SNPs) and small insertions/deletions.

Main Results:

• Identification of 4535 SVs, including two novel deletions at 6q21.33 and one novel Alu element insertion at 5q33.3 associated with psoriasis.
• Confirmation of a previously reported deletion at 1q21.2.
• Discovery of a novel independent SNP (rs9378188) at 6q21.33, independently associated with psoriasis.
• Evidence suggests deletions at 6q21.33 may influence HLA-C expression, potentially linking them to psoriasis pathogenesis.

Conclusions:

• Construction of the most comprehensive SV map for psoriasis to date.
• Enrichment of the understanding of psoriasis's genetic architecture and pathogenesis.
• Emphasis on the significant impact of SVs in complex human diseases.