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全外显子组强直性脊柱炎研究表明其与炎症性肠病存在额外的共同遗传背景。

Exome-wide study of ankylosing spondylitis demonstrates additional shared genetic background with inflammatory bowel disease.

作者信息

Robinson Philip C, Leo Paul J, Pointon Jennifer J, Harris Jessica, Cremin Katie, Bradbury Linda A, Stebbings Simon, Harrison Andrew A, Duncan Emma L, Evans David M, Wordsworth Paul B, Brown Matthew A

机构信息

School of Medicine, Faculty of Medicine and Biomedical Sciences, University of Queensland, Brisbane, QLD, Australia.

University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital, Brisbane, QLD, Australia.

出版信息

NPJ Genom Med. 2016 May 4;1:16008. doi: 10.1038/npjgenmed.2016.8. eCollection 2016.

Abstract

Ankylosing spondylitis (AS) is a common chronic immune-mediated arthropathy affecting primarily the spine and pelvis. The condition is strongly associated with as well as other human leukocyte antigen variants and at least 47 individual non-MHC-associated variants. However, substantial additional heritability remains as yet unexplained. To identify further genetic variants associated with the disease, we undertook an association study of AS in 5,040 patients and 21,133 healthy controls using the Illumina Exomechip microarray. A novel association achieving genome-wide significance was noted at . Suggestive associations were demonstrated with common variants in , and and with a low-frequency variant in Two of the variants have been previously associated with inflammatory bowel disease (IBD; and ). These findings further increase the evidence for the marked similarity of genetic risk factors for IBD and AS, consistent with the two diseases having similar aetiopathogenesis.

摘要

强直性脊柱炎(AS)是一种常见的慢性免疫介导的关节病,主要影响脊柱和骨盆。该疾病与 以及其他人类白细胞抗原变体以及至少47种个体非MHC相关变体密切相关。然而,大量额外的遗传力仍未得到解释。为了确定与该疾病相关的进一步遗传变异,我们使用Illumina外显子芯片微阵列对5040例患者和21133例健康对照进行了AS的关联研究。在 发现了一个达到全基因组显著性的新关联。在 、 和 中的常见变体以及 在 中的一个低频变体显示出提示性关联。其中两个变体先前已与炎症性肠病(IBD; 和 )相关。这些发现进一步增加了IBD和AS遗传危险因素显著相似性的证据,这与两种疾病具有相似的病因发病机制一致。

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