Extended exome sequencing identifies BACH2 as a novel major risk locus for Addison's disease
Extended exome sequencing identifies BACH2 as a novel major risk locus for Addison's disease
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DOI：
10.1111/joim.12569
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发表时间：
2016-12-01
影响因子：
11.1
通讯作者：
Pielberg, G. R.
中科院分区：
文献类型：
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作者：
Eriksson, D.;Bianchi, M.;Pielberg, G. R.
背景自身免疫性疾病是世界范围内发病和死亡的主要原因之一。在阿狄森氏病中，肾上腺是破坏性自身免疫的目标。尽管是最常见的原因原发性肾上腺衰竭，鲜为人知的是其aetiology.MethodsTo了解Addison病的遗传背景，我们利用了广泛的特点，瑞典Addison登记处的患者。我们开发了一种扩展的外显子组捕获阵列，包括一组选定的1853个基因及其潜在的调控元件，用于测序479名阿狄森病患者和1394名对照。（rs62408233-A，OR = 2.01（1.71-2.37），P = 1.66 × 10（-15），病例/对照MAF 0.46/0.29）作为与Addison病发展相关的新基因。我们还证实了以前已知的协会与HLA complex. ConclusionWhile BACH 2以前曾报道与器官特异性自身免疫性疾病共同继承与阿狄森氏病，我们已经确定BACH 2作为一个主要的风险位点在阿狄森氏病，独立的伴随自身免疫性疾病。我们的研究结果可能使未来的研究对预防性疾病的治疗。
BackgroundAutoimmune disease is one of the leading causes of morbidity and mortality worldwide. In Addison's disease, the adrenal glands are targeted by destructive autoimmunity. Despite being the most common cause of primary adrenal failure, little is known about its aetiology.MethodsTo understand the genetic background of Addison's disease, we utilized the extensively characterized patients of the Swedish Addison Registry. We developed an extended exome capture array comprising a selected set of 1853 genes and their potential regulatory elements, for the purpose of sequencing 479 patients with Addison's disease and 1394 controls.ResultsWe identified BACH2 (rs62408233-A, OR = 2.01 (1.71-2.37), P = 1.66 x 10(-15), MAF 0.46/0.29 in cases/controls) as a novel gene associated with Addison's disease development. We also confirmed the previously known associations with the HLA complex.ConclusionWhilst BACH2 has been previously reported to associate with organ-specific autoimmune diseases co-inherited with Addison's disease, we have identified BACH2 as a major risk locus in Addison's disease, independent of concomitant autoimmune diseases. Our results may enable future research towards preventive disease treatment.