{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T20:00:28Z","timestamp":1792440028460,"version":"4.5.0"},"reference-count":36,"publisher":"Royal College of Psychiatrists","issue":"1","license":[{"start":{"date-parts":[[2022,12,12]],"date-time":"2022-12-12T00:00:00Z","timestamp":1670803200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","award":["R01-MH114593"],"award-info":[{"award-number":["R01-MH114593"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["Br J Psychiatry"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:sec id=\"S0007125022001799_sec_a1\"><jats:title>Background<\/jats:title><jats:p>Psychotic disorders and schizotypal traits aggregate in the relatives of probands with schizophrenia. It is currently unclear how variability in symptom dimensions in schizophrenia probands and their relatives is associated with polygenic liability to psychiatric disorders.<\/jats:p><\/jats:sec><jats:sec id=\"S0007125022001799_sec_a2\"><jats:title>Aims<\/jats:title><jats:p>To investigate whether polygenic risk scores (PRSs) can predict symptom dimensions in members of multiplex families with schizophrenia.<\/jats:p><\/jats:sec><jats:sec id=\"S0007125022001799_sec_a3\" sec-type=\"methods\"><jats:title>Method<\/jats:title><jats:p>The largest genome-wide data-sets for schizophrenia, bipolar disorder and major depressive disorder were used to construct PRSs in 861 participants from the Irish Study of High-Density Multiplex Schizophrenia Families. Symptom dimensions were derived using the Operational Criteria Checklist for Psychotic Disorders in participants with a history of a psychotic episode, and the Structured Interview for Schizotypy in participants without a history of a psychotic episode. Mixed-effects linear regression models were used to assess the relationship between PRS and symptom dimensions across the psychosis spectrum.<\/jats:p><\/jats:sec><jats:sec id=\"S0007125022001799_sec_a4\" sec-type=\"results\"><jats:title>Results<\/jats:title><jats:p>Schizophrenia PRS is significantly associated with the negative\/disorganised symptom dimension in participants with a history of a psychotic episode (<jats:italic>P<\/jats:italic> = 2.31 \u00d7 10<jats:sup>\u22124<\/jats:sup>) and negative dimension in participants without a history of a psychotic episode (<jats:italic>P<\/jats:italic> = 1.42 \u00d7 10<jats:sup>\u22123<\/jats:sup>). Bipolar disorder PRS is significantly associated with the manic symptom dimension in participants with a history of a psychotic episode (<jats:italic>P<\/jats:italic> = 3.70 \u00d7 10<jats:sup>\u22124<\/jats:sup>). No association with major depressive disorder PRS was observed.<\/jats:p><\/jats:sec><jats:sec id=\"S0007125022001799_sec_a5\" sec-type=\"conclusions\"><jats:title>Conclusions<\/jats:title><jats:p>Polygenic liability to schizophrenia is associated with higher negative\/disorganised symptoms in participants with a history of a psychotic episode and negative symptoms in participants without a history of a psychotic episode in multiplex families with schizophrenia. These results provide genetic evidence in support of the spectrum model of schizophrenia, and support the view that negative and disorganised symptoms may have greater genetic basis than positive symptoms, making them better indices of familial liability to schizophrenia.<\/jats:p><\/jats:sec>","DOI":"10.1192\/bjp.2022.179","type":"journal-article","created":{"date-parts":[[2022,12,12]],"date-time":"2022-12-12T09:38:31Z","timestamp":1670837911000},"page":"301-308","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":25,"title":["Relationship between polygenic risk scores and symptom dimensions of schizophrenia and schizotypy in multiplex families with schizophrenia"],"prefix":"10.1192","volume":"223","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6585-5523","authenticated-orcid":false,"given":"Mohammad","family":"Ahangari","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Bustamante","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Kirkpatrick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tan-Hoang","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian C.","family":"Verrelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayman","family":"Fanous","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth 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Author(s), 2022. Published by Cambridge University Press on behalf of the Royal College of Psychiatrists","name":"copyright","label":"Copyright","group":{"name":"copyright_and_licensing","label":"Copyright and Licensing"}},{"value":"This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http:\/\/creativecommons.org\/licenses\/by\/4.0), which permits unrestricted re-use, distribution and reproduction, provided the original article is properly cited.","name":"license","label":"License","group":{"name":"copyright_and_licensing","label":"Copyright and Licensing"}},{"value":"This content has been made available to all.","name":"free","label":"Free to read"}]}}