{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T06:00:16Z","timestamp":1778220016749,"version":"3.51.4"},"reference-count":63,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2024,6,26]],"date-time":"2024-06-26T00:00:00Z","timestamp":1719360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Esotropia and exotropia in the entity of comitant strabismus are multifactorial diseases with both genetic and environmental backgrounds. Idiopathic superior oblique muscle palsy, as the predominant entity of non-comitant (paralytic) strabismus, also has a genetic background, as evidenced by varying degrees of muscle hypoplasia. A genome-wide association study (GWAS) was conducted of 711 Japanese patients with esotropia (n= 253), exotropia (n = 356), and idiopathic superior oblique muscle palsy (n = 102). The genotypes of single nucleotide polymorphisms (SNPs) were determined by Infinium Asian Screening Array. Three control cohorts from the Japanese population were used: two cohorts from BioBank Japan (BBJ) and the Nagahama Cohort. BBJ (180K) was genotyped by a different array, Illumina Infinium OmniExpressExome or HumanOmniExpress, while BBJ (ASA) and the Nagahama Cohort were genotyped by the same Asian array. After quality control of SNPs and individuals, common SNPs between the case cohort and the control cohort were chosen in the condition of genotyping by different arrays, while all SNPs genotyped by the same array were used for SNP imputation. The SNPs imputed with R-square values \u2265 0.3 were used to compare the case cohort of each entity or the combined entity with the control cohort. In comparison with BBJ (180K), the esotropia group and the exotropia group showed CDCA7 and HLA-F, respectively, as candidate genes at a significant level of p &lt; 5 \u00d7 10\u22128, while the idiopathic superior oblique muscle palsy group showed DAB1 as a candidate gene which is involved in neuronal migration. DAB1 was also detected as a candidate in comparison with BBJ (ASA) and the Nagahama Cohort at a weak level of significance of p &lt; 1 \u00d7 10\u22126. In comparison with BBJ (180K), RARB (retinoic acid receptor-\u03b2) was detected as a candidate at a significant level of p &lt; 5 \u00d7 10\u22128 in the combined group of esotropia, exotropia, and idiopathic superior oblique muscle palsy. In conclusion, a series of GWASs with three different control cohorts would be an effective method with which to search for candidate genes for multifactorial diseases such as strabismus.<\/jats:p>","DOI":"10.3390\/ijms25136986","type":"journal-article","created":{"date-parts":[[2024,6,27]],"date-time":"2024-06-27T05:11:39Z","timestamp":1719465099000},"page":"6986","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Genome-Wide Association Study with Three Control Cohorts of Japanese Patients with Esotropia and Exotropia of Comitant Strabismus and Idiopathic Superior Oblique Muscle Palsy"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6570-0030","authenticated-orcid":false,"given":"Toshihiko","family":"Matsuo","sequence":"first","affiliation":[{"name":"Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama City 700-8558, Japan"},{"name":"Department of Ophthalmology, Okayama University Hospital, Okayama City 700-8558, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ichiro","family":"Hamasaki","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Okayama University Hospital, Okayama City 700-8558, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoichiro","family":"Kamatani","sequence":"additional","affiliation":[{"name":"Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo 108-8639, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takahisa","family":"Kawaguchi","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0890-0145","authenticated-orcid":false,"given":"Izumi","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fumihiko","family":"Matsuda","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akira","family":"Saito","sequence":"additional","affiliation":[{"name":"StaGen Co., Ltd., Tokyo 111-0051, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuyuki","family":"Nakazono","sequence":"additional","affiliation":[{"name":"StaGen Co., Ltd., Tokyo 111-0051, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shigeo","family":"Kamitsuji","sequence":"additional","affiliation":[{"name":"StaGen Co., Ltd., Tokyo 111-0051, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Zhang, J., Matsuo, T., Hamasaki, I., and Sato, K. 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