{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T12:34:12Z","timestamp":1753878852246,"version":"3.41.2"},"reference-count":57,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,5,16]],"date-time":"2024-05-16T00:00:00Z","timestamp":1715817600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes Brain and Behavior"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Reading disorders (RD) are human\u2010specific neuropsychological conditions associated with decoding printed words and\/or reading comprehension. So far only a handful of candidate genes segregated in families and 42 loci from genome\u2010wide association study (GWAS) have been identified that jointly provided little clues of pathophysiology. Leveraging human\u2010specific genomic information, we critically assessed the RD candidates for the first time and found substantial human\u2010specific features within. The GWAS candidates (i.e., population signals) were distinct from the familial counterparts and were more likely pleiotropic in neuropsychiatric traits and to harbor human\u2010specific regulatory elements (HSREs). Candidate genes associated with human cortical morphology indeed showed human\u2010specific expression in adult brain cortices, particularly in neuroglia likely regulated by HSREs. Expression levels of candidate genes across human brain developmental stages showed a clear pattern of uplifted expression in early brain development crucial to RD development. Following the new insights and loci pleiotropic in cognitive traits, we identified four novel genes from the GWAS sub\u2010significant associations (i.e., <jats:italic>FOXO3<\/jats:italic>, <jats:italic>MAPT<\/jats:italic>, <jats:italic>KMT2E<\/jats:italic> and <jats:italic>HTT<\/jats:italic>) and the Semaphorin gene family with functional priors (i.e., <jats:italic>SEMA3A<\/jats:italic>, <jats:italic>SEMA3E<\/jats:italic> and <jats:italic>SEMA5B<\/jats:italic>). These novel genes were related to neuronal plasticity and disorders, mostly conserved the pattern of uplifted expression in early brain development and had evident expression in cortical neuroglial cells. Our findings jointly illuminated the association of RD with neuroglia regulation\u2014an emerging hotspot in studying neurodevelopmental disorders, and highlighted the need of improving RD phenotyping to avoid jeopardizing future genetic studies of RD.<\/jats:p>","DOI":"10.1111\/gbb.12899","type":"journal-article","created":{"date-parts":[[2024,5,16]],"date-time":"2024-05-16T11:50:38Z","timestamp":1715860238000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Human\u2010specific insights into candidate genes and boosted discoveries of novel loci illuminate roles of neuroglia in reading disorders"],"prefix":"10.1111","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5774-5941","authenticated-orcid":false,"given":"Wen\u2010Hua","family":"Wei","sequence":"first","affiliation":[{"name":"Centre for Biostatistics, Division of Population Health, Health Services Research and Primary Care The University of Manchester  Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaowei","family":"Ma","sequence":"additional","affiliation":[{"name":"Hebei Key Laboratory of Children's Cognition and Digital Education and School of Foreign Languages Langfang Normal University  Langfang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Fu","sequence":"additional","affiliation":[{"name":"School of Data Science Fudan University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8354-7698","authenticated-orcid":false,"given":"Ranran","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Maternal and Child Health and MOE (Ministry of Education) Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Guo","sequence":"additional","affiliation":[{"name":"Centre for Biostatistics, Division of Population Health, Health Services Research and Primary Care The University of Manchester  Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,5,16]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genet-120213-092236"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-020-00305-9"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/03054985.2020.1765756"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/03054985.2020.1747418"},{"issue":"282","key":"e_1_2_7_6_1","article-title":"The interface between genetics and psychology: lessons from developmental dyslexia","volume":"2015","author":"Bishop DV","year":"1806","journal-title":"Proc Biol Sci"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-clinpsy-032814-112842"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.14149"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyg.2020.00327"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpp.13324"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-022-01192-y"},{"key":"e_1_2_7_12_1","first-page":"12","article-title":"Early language exposure affects neural mechanisms of semantic representations","volume":"12","author":"Wang X","year":"2023","journal-title":"elife"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-psych-122216-011701"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-020-00898-x"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-022-02250-z"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-021-02289-w"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-022-00568-4"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-022-00554-w"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06338-4"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s10038-020-0821-z"},{"key":"e_1_2_7_21_1","first-page":"3","article-title":"Leveraging primate\u2010specific genomic information for genetic studies of complex diseases. 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