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We report evidence for association of rs61749465A&gt;G with BPD (<jats:italic>p<\/jats:italic> = 0.0009). rs61749465 is located in the N\u2010terminal of the BRCT1 domain of MCPH1. Bioinformatic analysis predicted the Asp61Gly substitution to be damaging to MCPH1 function. A second <jats:italic>MCPH1<\/jats:italic> BRCT1 domain variant (rs199422124C&gt;G; p.Thr27Arg), reported to cause autosomal recessive microcephaly, was not detected in the participants tested here. We sought to characterize the functional effects of these variants on <jats:italic>MCPH1<\/jats:italic> function. Cell count assays indicated that rs199422124 allele G had a greater impact on cell survival compared to the G allele of rs61749465. Gene expression analysis combined with gene network and pathway analysis indicated that rs61749465 allele G may impact protein translation and cell cycle control.<\/jats:p><jats:p>The evidence for association between rs61749465A&gt;G and psychosis in both BPD and SCZ warrants further replication. Likewise, the data from the functional analyses point to molecular mechanisms that may underlie the proposed <jats:italic>MCPH1<\/jats:italic> mediated risk of psychosis and pathogenesis in autosomal recessive microcephaly require additional experimental validation.<\/jats:p>","DOI":"10.1002\/ajmg.b.32722","type":"journal-article","created":{"date-parts":[[2019,3,12]],"date-time":"2019-03-12T04:44:59Z","timestamp":1552365899000},"page":"258-265","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Genetic association and functional characterization of <i>MCPH1<\/i> gene variation in bipolar disorder and schizophrenia"],"prefix":"10.1002","volume":"180","author":[{"given":"Mariam M.","family":"Al Eissa","sequence":"first","affiliation":[{"name":"Molecular Psychiatry Laboratory, Division of Psychiatry University College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sally I.","family":"Sharp","sequence":"additional","affiliation":[{"name":"Molecular Psychiatry Laboratory, Division of Psychiatry University College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niamh L.","family":"O'Brien","sequence":"additional","affiliation":[{"name":"Molecular Psychiatry Laboratory, Division of Psychiatry University College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessia","family":"Fiorentino","sequence":"additional","affiliation":[{"name":"Molecular Psychiatry Laboratory, Division of Psychiatry University College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas J.","family":"Bass","sequence":"additional","affiliation":[{"name":"Molecular Psychiatry Laboratory, Division of Psychiatry University College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Curtis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1567-2240","authenticated-orcid":false,"given":"Andrew","family":"McQuillin","sequence":"additional","affiliation":[{"name":"Department of Genetics, Evolution and Environment, UCL Genetics Institute, University College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,3,11]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"crossref","unstructured":"AdzhubeiI JordanDM SunyaevSR.2013. 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