全基因组关联研究确定了导致恶性贫血的五个风险位点。
Genome-wide association study identifies five risk loci for pernicious anemia.
机构信息
Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.
Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
出版信息
Nat Commun. 2021 Jun 18;12(1):3761. doi: 10.1038/s41467-021-24051-6.
Pernicious anemia is a rare condition characterized by vitamin B12 deficiency anemia due to lack of intrinsic factor, often caused by autoimmune gastritis. Patients with pernicious anemia have a higher incidence of other autoimmune disorders, such as type 1 diabetes, vitiligo, and autoimmune thyroid issues. Therefore, the disease has a clear autoimmune basis, although the genetic susceptibility factors have thus far remained poorly studied. We conduct a genome-wide association study meta-analysis in 2166 cases and 659,516 European controls from population-based biobanks and identify genome-wide significant signals in or near the PTPN22 (rs6679677, p = 1.91 × 10, OR = 1.63), PNPT1 (rs12616502, p = 3.14 × 10, OR = 1.70), HLA-DQB1 (rs28414666, p = 1.40 × 10, OR = 1.38), IL2RA (rs2476491, p = 1.90 × 10, OR = 1.22) and AIRE (rs74203920, p = 2.33 × 10, OR = 1.83) genes, thus providing robust associations between pernicious anemia and genetic risk factors.
恶性贫血是一种罕见的疾病，其特征是由于内因子缺乏导致维生素 B12 缺乏性贫血，通常由自身免疫性胃炎引起。恶性贫血患者其他自身免疫性疾病的发病率较高，如 1 型糖尿病、白癜风和自身免疫性甲状腺问题。因此，尽管遗传易感性因素迄今仍研究甚少，但该疾病具有明确的自身免疫基础。我们在基于人群的生物库中的 2166 例病例和 659516 名欧洲对照中进行了全基因组关联研究荟萃分析，在 PTPN22（rs6679677，p=1.91×10-8，OR=1.63）、PNPT1（rs12616502，p=3.14×10-8，OR=1.70）、HLA-DQB1（rs28414666，p=1.40×10-8，OR=1.38）、IL2RA（rs2476491，p=1.90×10-8，OR=1.22）和 AIRE（rs74203920，p=2.33×10-8，OR=1.83）基因中发现了全基因组显著信号，从而为恶性贫血与遗传风险因素之间提供了有力的关联。
Zotero 插件