Abstract：
BACKGROUND: According to the common disease/rare variant 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 χ2 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 = 9.99 × 10-5), and the single-nucleotide polymorphism with the strongest association was rs199780529 (p_combine = 1 × 10-3, p_meta = 2 × 10-3).
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.
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 χ2 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 = 9.99 × 10-5), and the single-nucleotide polymorphism with the strongest association was rs199780529 (p_combine = 1 × 10-3, p_meta = 2 × 10-3).
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.
摘要：
背景：根据常见病/罕见变异（CDRV）假说，研究罕见变异在复杂疾病中的作用很重要。已经证明了罕见变异与牛皮癣的关联，但罕见变异型与银屑病特定临床亚型之间的关联尚未得到研究.
方法：基于基因和基因水平的荟萃分析是从我们以前的研究数据集（2,483例滴状银屑病患者和8,292例非滴状银屑病患者）中提取的数据进行基因分型。然后，对位于MED12L中的罕见功能丧失变体进行单倍型分析，并对MED12L进行蛋白质功能预测。每个阶段的基于基因的分析具有中等显著性阈值(P<0.05)。然后对三个潜在基因进行卡方检验,并使用合并的基于基因的分析来确认结果。我们还对位于鉴定基因上的功能变异进行了关联分析和荟萃分析。
结果：通过这些基因水平分析，我们确定MED12L是点滴状银屑病易感基因（P=9.99x10-5），关联最强的单核苷酸多态性（SNP）是rs199780529（P_combine=1x10-3，P_meta=2x10-3）。
结论：在我们的研究中，在中国汉族人群中证实了点滴状银屑病特异性亚型相关易感基因.这些发现有助于更好地理解银屑病的不同亚型。
方法：基于基因和基因水平的荟萃分析是从我们以前的研究数据集（2,483例滴状银屑病患者和8,292例非滴状银屑病患者）中提取的数据进行基因分型。然后，对位于MED12L中的罕见功能丧失变体进行单倍型分析，并对MED12L进行蛋白质功能预测。每个阶段的基于基因的分析具有中等显著性阈值(P<0.05)。然后对三个潜在基因进行卡方检验,并使用合并的基于基因的分析来确认结果。我们还对位于鉴定基因上的功能变异进行了关联分析和荟萃分析。
结果：通过这些基因水平分析，我们确定MED12L是点滴状银屑病易感基因（P=9.99x10-5），关联最强的单核苷酸多态性（SNP）是rs199780529（P_combine=1x10-3，P_meta=2x10-3）。
结论：在我们的研究中，在中国汉族人群中证实了点滴状银屑病特异性亚型相关易感基因.这些发现有助于更好地理解银屑病的不同亚型。
