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Age\u2010related hearing impairment (ARHI) is considered an unpreventable disorder. We aimed to detect specific genetic variants that are potentially related to ARHI via genome\u2010wide association study (GWAS). <jats:italic>Methods<\/jats:italic>. A sample of 131 dizygotic twins was genotyped for single\u2010nucleotide polymorphism\u2010 (SNP\u2010) based GWAS. Gene\u2010based test was performed using VEGAS2. Pathway enrichment analysis was conducted by PASCAL. <jats:italic>Results<\/jats:italic>. The twins are with a median age of 49 years, of which 128 were females and 134 were males. rs6633657 was the only SNP that reached the genome\u2010wide significance level for better ear hearing level (BEHL) at 2.0\u2009kHz (<jats:italic>P<\/jats:italic> = 1.19 \u00d7 10<jats:sup>\u22128<\/jats:sup>). Totally, 9, 10, 42, 7, 17, and 5 SNPs were suggestive evidence level for (<jats:italic>P<\/jats:italic> &lt; 1 \u00d7 10<jats:sup>\u22125<\/jats:sup>) BEHLs at 0.5, 1.0, 2.0, 4.0, and 8.0\u2009kHz and pure tone average (PTA), respectively. Several promising genetic regions in chromosomes (near the C20orf196, AQPEP, UBQLN3, OR51B5, OR51I2, OR52D1, GLTP, GIT2, and PARK2) nominally associated with ARHI were identified. Gene\u2010based analysis revealed 165, 173, 77, 178, 170, and 145 genes nominally associated with BEHLs at 0.5, 1.0, 2.0, 4.0, and 8.0\u2009kHz and PTA, respectively (<jats:italic>P<\/jats:italic> &lt; 0.05). For BEHLs at 0.5, 1.0, and 2.0\u2009kHz, the main enriched pathways were phosphatidylinositol signaling system, regulation of ornithine decarboxylase, eukaryotic translation initiation factor (EIF) pathway, amine compound solute carrier (SLC) transporters, synthesis of phosphoinositides (PIPS) at the plasma membrane, and phosphatidylinositols (PI) metabolism. <jats:italic>Conclusions<\/jats:italic>. The genetic variations reported herein are significantly involved in functional genes and regulatory domains that mediate ARHI pathogenesis. These findings provide clues for the further unraveling of the molecular physiology of hearing functions and identifying novel diagnostic biomarkers and therapeutic targets of ARHI.<\/jats:p>","DOI":"10.1155\/2021\/3629624","type":"journal-article","created":{"date-parts":[[2021,7,19]],"date-time":"2021-07-19T19:05:09Z","timestamp":1626721509000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["A Genome\u2010Wide Association Study of Age\u2010Related Hearing Impairment in Middle\u2010 and Old\u2010Aged Chinese Twins"],"prefix":"10.1155","volume":"2021","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3074-7004","authenticated-orcid":false,"given":"Haiping","family":"Duan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0424-2619","authenticated-orcid":false,"given":"Wanxue","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7747-7649","authenticated-orcid":false,"given":"Weijing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5245-2899","authenticated-orcid":false,"given":"Hainan","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3338-7187","authenticated-orcid":false,"given":"Bingling","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3891-3695","authenticated-orcid":false,"given":"Yan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2265-5414","authenticated-orcid":false,"given":"Chunsheng","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5289-2552","authenticated-orcid":false,"given":"Yili","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4746-0074","authenticated-orcid":false,"given":"Zengchang","family":"Pang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9308-9371","authenticated-orcid":false,"given":"Dongfeng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,7,19]]},"reference":[{"key":"e_1_2_9_1_2","first-page":"661","article-title":"Epidemiologic study on hearing impairment and ear diseases in old people","volume":"41","author":"Liu C.","year":"2006","journal-title":"Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi"},{"key":"e_1_2_9_2_2","first-page":"1147","article-title":"Prevalence and influence factors of hearing impairment among rural senior people in Qingdao municipality","volume":"29","author":"Liu Taoran","year":"2013","journal-title":"Chin Journal of Public Health"},{"key":"e_1_2_9_3_2","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2015.00276"},{"key":"e_1_2_9_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.heares.2013.01.021"},{"key":"e_1_2_9_5_2","doi-asserted-by":"publisher","DOI":"10.1017\/thg.2015.35"},{"key":"e_1_2_9_6_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1532-5415.2001.4911245.x"},{"key":"e_1_2_9_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/62.4.447"},{"key":"e_1_2_9_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/62.11.1294"},{"key":"e_1_2_9_9_2","doi-asserted-by":"publisher","DOI":"10.1044\/1059-0889(2009\/08-0035)"},{"key":"e_1_2_9_10_2","doi-asserted-by":"publisher","DOI":"10.1097\/EDE.0b013e318245996e"},{"key":"e_1_2_9_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glu245"},{"key":"e_1_2_9_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2009.234"},{"key":"e_1_2_9_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn402"},{"key":"e_1_2_9_14_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006371"},{"key":"e_1_2_9_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/ahg.12181"},{"key":"e_1_2_9_16_2","doi-asserted-by":"publisher","DOI":"10.1097\/AUD.0000000000000610"},{"key":"e_1_2_9_17_2","doi-asserted-by":"publisher","DOI":"10.1017\/thg.2017.42"},{"key":"e_1_2_9_18_2","doi-asserted-by":"publisher","DOI":"10.1017\/thg.2016.98"},{"key":"e_1_2_9_19_2","first-page":"260","article-title":"Twin zygosity. 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