Tavernier Lisse J M, Vanpoucke Thomas, Schrauwen Isabelle, Van Camp Guy, Fransen Erik
Center of Medical Genetics, University of Antwerp & Antwerp University Hospital, 2650 Antwerp, Belgium.
Center for Statistical Genetics, Department of Neurology, Gertrude H. Sergievsky Center, Columbia University Medical Center, New York, NY 10032, USA.
J Clin Med. 2022 Nov 26;11(23):6978. doi: 10.3390/jcm11236978.
Otosclerosis is one of the most common causes of hearing loss in young adults. It has a prevalence of 0.3-0.4% in the European population. Clinical symptoms usually occur between the second and fifth decade of life. Different studies have been performed to unravel the genetic architecture of the disease. Recently, a genome-wide association study (GWAS) identified 15 novel risk loci and replicated the regions of three previously reported candidate genes. In this study, seven candidate genes from the GWAS were resequenced using single molecule molecular inversion probes (smMIPs). smMIPs were used to capture the exonic regions and the 3' and 5' untranslated regions (UTR). Discovered variants were tested for association with the disease using single variant and gene-based association analysis. The single variant results showed that 13 significant variants were associated with otosclerosis. Associated variants were found in five of the seven genes studied here, including , , , and . Conversely, burden testing did not show a major role of rare variants in the disease. In conclusion, this study was able to replicate five out of seven candidate genes reported in the previous GWAS. This association is likely mainly driven by common variants.
耳硬化症是年轻成年人听力丧失的最常见原因之一。在欧洲人群中的患病率为0.3 - 0.4%。临床症状通常出现在人生的第二个和第五个十年之间。已经进行了不同的研究来揭示该疾病的遗传结构。最近，一项全基因组关联研究（GWAS）确定了15个新的风险位点，并重复了三个先前报道的候选基因所在区域。在本研究中，使用单分子分子倒置探针（smMIPs）对来自GWAS的七个候选基因进行了重测序。smMIPs用于捕获外显子区域以及3'和5'非翻译区（UTR）。使用单变体和基于基因的关联分析测试发现的变体与该疾病的关联。单变体结果表明，13个显著变体与耳硬化症相关。在此研究的七个基因中的五个中发现了相关变体，包括 、 、 、 和 。相反，负荷测试未显示罕见变体在该疾病中的主要作用。总之，本研究能够重复先前GWAS中报道的七个候选基因中的五个。这种关联可能主要由常见变体驱动。
