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Rare MED12L variants is associated with susceptibility to guttate psoriasis in the Han Chinese Population.

INTRODUCTION: According to the common disease/rare variant (CDRV) hypothesis, it is important to study the role of rare variants in complex diseases. The association of rare variants with psoriasis has been demonstrated, but the association between rare variants and specific clinical subtypes of psoriasis has not been investigated.

METHODS: Gene-based and gene-level meta-analyses were performed on data extracted from our previous study data sets(2,483 patients with guttate psoriasis and 8,292 patients with non-guttate psoriasis) for genotyping. Then, haplotype analysis was performed for rare loss-of-function variants located in MED12L, and protein function prediction was performed for MED12L. Gene-based analysis at each stage had a moderate significance threshold (P < 0.05). A chi-square test was then conducted on the three potential genes, and the merged gene-based analysis was used to confirm the results. We also conducted association analysis and meta-analysis for functional variants located on the identified gene.

RESULTS: Through these gene-level analyses, we determined that MED12L is a guttate psoriasis susceptibility gene (P=9.99x10-5), and the single-nucleotide polymorphism (SNP) with the strongest association was rs199780529 (P_combine=1x10-3, P_meta=2x10-3).

CONCLUSIONS: In our study, a guttate psoriasis-specific subtype-associated susceptibility gene was confirmed in a Chinese Han population. These findings contribute to a better genetic understanding of different subtypes of psoriasis.

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