Xianfa Tang, Hui Cheng, Lu Cheng, Bo Liang, Mengyun Chen, Xiaodong Zheng, Fengli Xiao
{"title":"中国汉族人群中与白癜风相关的 10q22.1 编码变异的鉴定","authors":"Xianfa Tang, Hui Cheng, Lu Cheng, Bo Liang, Mengyun Chen, Xiaodong Zheng, Fengli Xiao","doi":"10.1089/gtmb.2023.0027","DOIUrl":null,"url":null,"abstract":"<p><p><b><i>Objective:</i></b> This study aims to identify causal variants associated with vitiligo in an expanded region of 10q22.1. <b><i>Materials and Methods:</i></b> 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 <i>SLC29A3</i> and <i>CDH23</i> 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. <b><i>Results:</i></b> A missense SNP in <i>SLC29A3</i>, rs2252996, showed strong evidence of association with vitiligo (<i>p</i> = 1.34 × 10<sup>-8</sup>, odds ratio [OR] = 0.82). Three synonymous SNPs (rs1084004 in <i>SLC29A3</i>; rs12218559 and rs10999978 in <i>CDH23</i>) provided suggestive evidence of association for vitiligo (<i>p</i> = 1.69 × 10<sup>-6</sup>, OR = 0.84; <i>p</i> = 9.47 × 10<sup>-5</sup>, OR = 1.18; <i>p</i> = 6.90 × 10<sup>-4</sup>, OR = 1.16, respectively). Stepwise conditional analyses identified two significant independent disease-associated signals from the four SNPs (both <i>p</i> < 0.05; both D' = 0.03; and <i>r<sup>2</sup></i> = 0.00). <b><i>Conclusion:</i></b> The study identifies four genetic coding variants in <i>SLC29A3</i> and <i>CDH23</i> 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.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":"28 3","pages":"123-130"},"PeriodicalIF":1.1000,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Identification of Coding Variants in 10q22.1 Associated with Vitiligo in the Chinese Han Population.\",\"authors\":\"Xianfa Tang, Hui Cheng, Lu Cheng, Bo Liang, Mengyun Chen, Xiaodong Zheng, Fengli Xiao\",\"doi\":\"10.1089/gtmb.2023.0027\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><b><i>Objective:</i></b> This study aims to identify causal variants associated with vitiligo in an expanded region of 10q22.1. <b><i>Materials and Methods:</i></b> 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 <i>SLC29A3</i> and <i>CDH23</i> 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. <b><i>Results:</i></b> A missense SNP in <i>SLC29A3</i>, rs2252996, showed strong evidence of association with vitiligo (<i>p</i> = 1.34 × 10<sup>-8</sup>, odds ratio [OR] = 0.82). Three synonymous SNPs (rs1084004 in <i>SLC29A3</i>; rs12218559 and rs10999978 in <i>CDH23</i>) provided suggestive evidence of association for vitiligo (<i>p</i> = 1.69 × 10<sup>-6</sup>, OR = 0.84; <i>p</i> = 9.47 × 10<sup>-5</sup>, OR = 1.18; <i>p</i> = 6.90 × 10<sup>-4</sup>, OR = 1.16, respectively). Stepwise conditional analyses identified two significant independent disease-associated signals from the four SNPs (both <i>p</i> < 0.05; both D' = 0.03; and <i>r<sup>2</sup></i> = 0.00). <b><i>Conclusion:</i></b> The study identifies four genetic coding variants in <i>SLC29A3</i> and <i>CDH23</i> 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.</p>\",\"PeriodicalId\":12603,\"journal\":{\"name\":\"Genetic testing and molecular biomarkers\",\"volume\":\"28 3\",\"pages\":\"123-130\"},\"PeriodicalIF\":1.1000,\"publicationDate\":\"2024-03-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Genetic testing and molecular biomarkers\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1089/gtmb.2023.0027\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Genetic testing and molecular biomarkers","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1089/gtmb.2023.0027","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
Identification of Coding Variants in 10q22.1 Associated with Vitiligo in the Chinese Han Population.
Objective: This study aims to identify causal variants associated with vitiligo in an expanded region of 10q22.1. Materials and Methods: 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 SLC29A3 and CDH23 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. Results: A missense SNP in SLC29A3, rs2252996, showed strong evidence of association with vitiligo (p = 1.34 × 10-8, odds ratio [OR] = 0.82). Three synonymous SNPs (rs1084004 in SLC29A3; rs12218559 and rs10999978 in CDH23) provided suggestive evidence of association for vitiligo (p = 1.69 × 10-6, OR = 0.84; p = 9.47 × 10-5, OR = 1.18; p = 6.90 × 10-4, OR = 1.16, respectively). Stepwise conditional analyses identified two significant independent disease-associated signals from the four SNPs (both p < 0.05; both D' = 0.03; and r2 = 0.00). Conclusion: The study identifies four genetic coding variants in SLC29A3 and CDH23 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.
期刊介绍:
Genetic Testing and Molecular Biomarkers is the leading peer-reviewed journal covering all aspects of human genetic testing including molecular biomarkers. The Journal provides a forum for the development of new technology; the application of testing to decision making in an increasingly varied set of clinical situations; ethical, legal, social, and economic aspects of genetic testing; and issues concerning effective genetic counseling. This is the definitive resource for researchers, clinicians, and scientists who develop, perform, and interpret genetic tests and their results.
Genetic Testing and Molecular Biomarkers coverage includes:
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Risk assessment-
Carrier detection in individuals, couples, and populations-
Novel methods and new instrumentation for genetic testing-
Results of molecular, biochemical, and cytogenetic testing-
Genetic counseling