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

Abstract

Background Structural variations (SVs; defined as DNA variants ≥ 50 base pairs) have been associated with various complex human diseases. However, research to screen the whole genome for SVs predisposing to psoriasis is lacking. Objectives To investigate the association of SVs and psoriasis. Methods Using imputation, we performed a genome-wide screen of SVs on five independent cohorts with 45 386 participants from the Han Chinese population.

Genome‐wide scan for structural variation underlying psoriasis

“…Zhen et al . identify two novel deletions close to HLA‐C 4 . Conditional analysis suggests that each contributes independently of HLA‐C*06:02 to psoriasis risk, and both are associated with increased expression of HLA‐C , highlighting a possible disease mechanism.…”

“…The picture is unclear for the well‐known LCE3B/C deletion. This SV is believed to have a mechanistic role in psoriasis, 5,6 a conclusion supported by only two of the three cohorts in which conditional analysis with local SNPs could be performed 4 …”

“…In this issue of the BJD , Zhen et al . report a thorough evaluation of the contribution of SVs to psoriasis susceptibility, using five Han Chinese case–control studies 4 . First, they performed extensive validation analysis to show that, with appropriate SV reference data, SVs can be imputed into targeted sequencing data or microarray genotype data with reasonable confidence.…”

“…2,3 In this issue of the BJD, Zhen et al report a thorough evaluation of the contribution of SVs to psoriasis susceptibility, using five Han Chinese case-control studies. 4 First, they performed extensive validation analysis to show that, with appropriate SV reference data, SVs can be imputed into targeted sequencing data or microarray genotype data with reasonable confidence. Next, their genome-wide meta-analysis highlighted significant SV associations with psoriasis at known susceptibility loci harbouring the HLA-C, IL12B and LCE3B/C genes.…”

“…Zhen et al have not found convincing evidence that the Alu element insertion identified at IL12B is causal, its association signal being ameliorated when conditioning on known susceptibility SNPs in the region. 4 The picture is unclear for the well-known LCE3B/C deletion. This SV is believed to have a mechanistic role in psoriasis, 5,6 a conclusion supported by only two of the three cohorts in which conditional analysis with local SNPs could be performed.…”