{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T00:20:32Z","timestamp":1793319632901,"version":"4.5.0"},"reference-count":73,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T00:00:00Z","timestamp":1668643200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015846","name":"Welsh Government","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100015846","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000615","name":"Fight for Sight UK","doi-asserted-by":"publisher","award":["24WG201"],"award-info":[{"award-number":["24WG201"]}],"id":[{"id":"10.13039\/501100000615","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000866","name":"Cardiff University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000866","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","award":["SRF-2015-08-005"],"award-info":[{"award-number":["SRF-2015-08-005"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>Myopia most often develops during school age, with the highest incidence in countries with intensive education systems. Interactions between genetic variants and educational exposure are hypothesized to confer susceptibility to myopia, but few such interactions have been identified. Here, we aimed to identify genetic variants that interact with education level to confer susceptibility to myopia. Two groups of unrelated participants of European ancestry from UK Biobank were studied. A \u2018Stage-I\u2019 sample of 88,334 participants whose refractive error (<jats:italic>avMSE<\/jats:italic>) was measured by autorefraction and a \u2018Stage-II\u2019 sample of 252,838 participants who self-reported their age-of-onset of spectacle wear (<jats:italic>AOSW<\/jats:italic>) but who did not undergo autorefraction. Genetic variants were prioritized via a 2-step screening process in the Stage-I sample: Step 1 was a genome-wide association study for <jats:italic>avMSE<\/jats:italic>; Step 2 was a variance heterogeneity analysis for <jats:italic>avMSE<\/jats:italic>. Genotype-by-education interaction tests were performed in the Stage-II sample, with University education coded as a binary exposure. On average, participants were 58 years-old and left full-time education when they were 18 years-old; 35% reported University level education. The 2-step screening strategy in the Stage-I sample prioritized 25 genetic variants (GWAS <jats:italic>P<\/jats:italic> &lt; 1e-04; variance heterogeneity <jats:italic>P<\/jats:italic> &lt; 5e-05). In the Stage-II sample, 19 of the 25 (76%) genetic variants demonstrated evidence of variance heterogeneity, suggesting the majority were true positives. Five genetic variants located near <jats:italic>GJD2<\/jats:italic>, <jats:italic>RBFOX1<\/jats:italic>, <jats:italic>LAMA2<\/jats:italic>, <jats:italic>KCNQ5<\/jats:italic> and <jats:italic>LRRC4C<\/jats:italic> had evidence of a genotype-by-education interaction in the Stage-II sample (<jats:italic>P<\/jats:italic> &lt; 0.002) and consistent evidence of a genotype-by-education interaction in the Stage-I sample. For all 5 variants, University-level education was associated with an increased effect of the risk allele. In this cohort, additional years of education were associated with an enhanced effect of genetic variants that have roles including axon guidance and the development of neuronal synapses and neural circuits.<\/jats:p>","DOI":"10.1371\/journal.pgen.1010478","type":"journal-article","created":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T18:31:56Z","timestamp":1668709916000},"page":"e1010478","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":20,"title":["Education interacts with genetic variants near GJD2, RBFOX1, LAMA2, KCNQ5 and LRRC4C to confer susceptibility to myopia"],"prefix":"10.1371","volume":"18","author":[{"given":"Rosie","family":"Clark","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfred","family":"Pozarickij","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5752-2510","authenticated-orcid":true,"given":"Pirro G.","family":"Hysi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8375-6879","authenticated-orcid":true,"given":"Kyoko","family":"Ohno-Matsui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathy","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5164-340X","authenticated-orcid":true,"given":"Jeremy 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