Department of Dermatology and Institute of Dermatology at No. 1 Hospital, Anhui Medical University, Hefei, China.
Key Laboratory of Dermatology, Ministry of Education, Hefei, China.
Genet Test Mol Biomarkers. 2024 Mar;28(3):123-130. doi: 10.1089/gtmb.2023.0027.
This study aims to identify causal variants associated with vitiligo in an expanded region of 10q22.1. We conducted a fine-scale deep analysis of the expanded 10q22.1 region using in a large genome-wide association studies dataset consisting of 1117 cases and 1701 controls through imputation. We selected five nominal coding single nucleotide polymorphisms (SNPs) located in and and genotyped them in an independent cohort of 2479 cases and 2451 controls in a Chinese Han population cohort using the Sequenom MassArray iPLEX1 system. A missense SNP in , rs2252996, showed strong evidence of association with vitiligo ( = 1.34 × 10, odds ratio [OR] = 0.82). Three synonymous SNPs (rs1084004 in ; rs12218559 and rs10999978 in ) provided suggestive evidence of association for vitiligo ( = 1.69 × 10, OR = 0.84; = 9.47 × 10, OR = 1.18; = 6.90 × 10, OR = 1.16, respectively). Stepwise conditional analyses identified two significant independent disease-associated signals from the four SNPs (both < 0.05; both D' = 0.03; and = 0.00). The study identifies four genetic coding variants in and on 10q22.1 that may contribute to vitiligo susceptibility with one missense variant affecting disease subphenotypes. The presence of multiple genetic variants underscores their significant role in the genetic pathogenesis of the disease.
本研究旨在鉴定与 10q22.1 扩展区域中白癜风相关的因果变异。我们通过对包含 1117 例病例和 1701 例对照的大型全基因组关联研究数据集进行精细深度分析，使用基于 imputation 的方法对扩展的 10q22.1 区域进行了分析。我们选择了位于 和 中的五个名义编码单核苷酸多态性（SNP），并在一个中国汉族人群的 2479 例病例和 2451 例对照的独立队列中使用 Sequenom MassArray iPLEX1 系统对其进行了基因分型。位于 中的错义 SNP rs2252996 与白癜风具有强烈的关联证据（ = 1.34 × 10，优势比 [OR] = 0.82）。三个同义 SNP（ 中的 rs1084004； 中的 rs12218559 和 rs10999978）为白癜风提供了提示性的关联证据（ = 1.69 × 10，OR = 0.84； = 9.47 × 10，OR = 1.18； = 6.90 × 10，OR = 1.16）。逐步条件分析从四个 SNP 中鉴定出两个与疾病相关的显著独立信号（均 < 0.05；均 D' = 0.03；均 = 0.00）。该研究鉴定出位于 10q22.1 上的四个遗传编码变异，它们可能通过影响疾病亚表型的一个错义变异而导致白癜风易感性。多个遗传变异的存在突出了它们在疾病遗传发病机制中的重要作用。
