{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T17:48:50Z","timestamp":1770745730541,"version":"3.49.0"},"reference-count":38,"publisher":"Royal College of Psychiatrists","issue":"1","license":[{"start":{"date-parts":[[2018,1,2]],"date-time":"2018-01-02T00:00:00Z","timestamp":1514851200000},"content-version":"unspecified","delay-in-days":3107,"URL":"https:\/\/www.cambridge.org\/core\/terms"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Psychiatry"],"published-print":{"date-parts":[[2009,7]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Psychiatric phenotypes are currently defined according to sets of descriptive criteria. Although many of these phenotypes are heritable, it would be useful to know whether any of the various diagnostic categories in current use identify cases that are particularly helpful for biological\u2013genetic research.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>To use genome-wide genetic association data to explore the relative genetic utility of seven different descriptive operational diagnostic categories relevant to bipolar illness within a large UK case\u2013control bipolar disorder sample.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>We analysed our previously published Wellcome Trust Case Control Consortium (WTCCC) bipolar disorder genome-wide association data-set, comprising 1868 individuals with bipolar disorder and 2938 controls genotyped for 276 122 single nucleotide polymorphisms (SNPs) that met stringent criteria for genotype quality. For each SNP we performed a test of association (bipolar disorder group v. control group) and used the number of associated independent SNPs statistically significant at<jats:italic>P<\/jats:italic>&lt;0.00001 as a metric for the overall genetic signal in the sample. We next compared this metric with that obtained using each of seven diagnostic subsets of the group with bipolar disorder: Research Diagnostic Criteria (RDC): bipolar I disorder; manic disorder; bipolar II disorder; schizoaffective disorder, bipolar type; DSM\u2013IV: bipolar I disorder; bipolar II disorder; schizoaffective disorder, bipolar type.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The RDC schizoaffective disorder, bipolar type (<jats:italic>v<\/jats:italic>. controls) stood out from the other diagnostic subsets as having a significant excess of independent association signals (<jats:italic>P<\/jats:italic>&lt;0.003) compared with that expected in samples of the same size selected randomly from the total bipolar disorder group data-set. The strongest association in this subset of participants with bipolar disorder was at rs4818065 (<jats:italic>P<\/jats:italic>= 2.42 \u00d7 10<jats:sup>\u20137<\/jats:sup>). Biological systems implicated included gamma amniobutyric acid (GABA)<jats:sub>A<\/jats:sub>receptors. Genes having at least one associated polymorphism at<jats:italic>P<\/jats:italic>&lt;10<jats:sup>\u20134<\/jats:sup>included<jats:italic>B3GALTS, A2BP1, GABRB1, AUTS2, BSN, PTPRG, GIRK2<\/jats:italic>and<jats:italic>CDH12<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings show that individuals with broadly defined bipolar schizoaffective features have either a particularly strong genetic contribution or that, as a group, are genetically more homogeneous than the other phenotypes tested. The results point to the importance of using diagnostic approaches that recognise this group of individuals. Our approach can be applied to similar data-sets for other psychiatric and non-psychiatric phenotypes.<\/jats:p><\/jats:sec>","DOI":"10.1192\/bjp.bp.108.061424","type":"journal-article","created":{"date-parts":[[2009,7,1]],"date-time":"2009-07-01T02:06:41Z","timestamp":1246414001000},"page":"23-29","source":"Crossref","is-referenced-by-count":76,"title":["Genetic utility of broadly defined bipolar schizoaffective disorder as a diagnostic concept"],"prefix":"10.1192","volume":"195","author":[{"given":"M. L.","family":"Hamshere","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E. K.","family":"Green","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I. R.","family":"Jones","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Jones","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V.","family":"Moskvina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.","family":"Kirov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.","family":"Grozeva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I.","family":"Nikolov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.","family":"Vukcevic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Caesar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.","family":"Gordon-Smith","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Fraser","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.","family":"Russell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.","family":"Breen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. St","family":"Clair","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. A.","family":"Collier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. H.","family":"Young","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I. N.","family":"Ferrier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Farmer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"McGuffin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P. A.","family":"Holmans","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. J.","family":"Owen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. C.","family":"O'Donovan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N.","family":"Craddock","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"Wellcome Trust Case Control Consortium","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"170","published-online":{"date-parts":[[2018,1,2]]},"reference":[{"key":"S0007125000007315_ref24","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1982.04290100031006"},{"key":"S0007125000007315_ref21","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1987.01800170083011"},{"key":"S0007125000007315_ref13","doi-asserted-by":"publisher","DOI":"10.1086\/519795"},{"key":"S0007125000007315_ref11","volume-title":"Diagnostic and Statistical Manual of Mental Disorder (4th edn) (DSM\u2013IV)","year":"1994"},{"key":"S0007125000007315_ref8","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1991.01810320088015"},{"key":"S0007125000007315_ref3","article-title":"Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls","volume":"447","year":"2007","journal-title":"Nature"},{"key":"S0007125000007315_ref2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.120"},{"key":"S0007125000007315_ref18","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.55.6.492"},{"key":"S0007125000007315_ref9","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.169.1.58"},{"key":"S0007125000007315_ref4","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2344"},{"key":"S0007125000007315_ref17","article-title":"Resemblance of psychotic symptoms and syndromes in affected sibling pairs from the Irish Study of High-Density Schizophrenia Families: evidence for possible etiologic heterogeneity","volume":"154","author":"Kendler","year":"1997","journal-title":"Am J Psychiatry"},{"key":"S0007125000007315_ref20","doi-asserted-by":"publisher","DOI":"10.1016\/0920-9964(95)00091-7"},{"key":"S0007125000007315_ref15","doi-asserted-by":"publisher","DOI":"10.1038\/ng.201"},{"key":"S0007125000007315_ref6","article-title":"Psychiatric diagnoses: the weak component of modern research","volume":"6","author":"Angst","year":"2007","journal-title":"World Psychiatry"},{"key":"S0007125000007315_ref38","doi-asserted-by":"publisher","DOI":"10.1007\/s10038-004-0145-4"},{"key":"S0007125000007315_ref26","volume-title":"The Genetics of Mental Disorders","author":"Slater","year":"1971"},{"key":"S0007125000007315_ref37","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.30530"},{"key":"S0007125000007315_ref22","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320600103"},{"key":"S0007125000007315_ref12","volume-title":"The ICD\u201310 Classification of Mental and Behavioural Disorders: Clinical Descriptions and Diagnostic Guidelines","year":"1992"},{"key":"S0007125000007315_ref10","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1978.01770300115013"},{"key":"S0007125000007315_ref5","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2008.45"},{"key":"S0007125000007315_ref34","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-5618.2007.00564.x"},{"key":"S0007125000007315_ref1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2203"},{"key":"S0007125000007315_ref16","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.126.7.983"},{"key":"S0007125000007315_ref25","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1993.01820230041004"},{"key":"S0007125000007315_ref19","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.schbul.a007138"},{"key":"S0007125000007315_ref7","first-page":"84","article-title":"Rethinking psychosis: the disadvantages of a dichotomous classification now outweigh the advantages","volume":"6","author":"Craddock","year":"2007","journal-title":"World Psychiatry"},{"key":"S0007125000007315_ref14","doi-asserted-by":"publisher","DOI":"10.1111\/j.0006-341X.1999.00997.x"},{"key":"S0007125000007315_ref28","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4001348"},{"key":"S0007125000007315_ref29","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4001541"},{"key":"S0007125000007315_ref30","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.160.4.680"},{"key":"S0007125000007315_ref31","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0447.2006.00763.x"},{"key":"S0007125000007315_ref32","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0447.2005.00744.x"},{"key":"S0007125000007315_ref33","article-title":"Schizoaffective disorder merges schizophrenia and bipolar disorders as one disease \u2013 there is no schizoaffective disorder","volume":"20","author":"Lake","year":"2007","journal-title":"Curr Opin Psychiatry"},{"key":"S0007125000007315_ref36","doi-asserted-by":"crossref","unstructured":"Craddock N , Jones L , Jones IR , Kirov G , Green EK , Grozeva D , et al. Strong genetic evidence for a selective influence of GABAA receptors on a component of the bipolar disorder phenotype. Mol Psychiatry 2008 July 1 (epub ahead of print).","DOI":"10.1038\/mp.2008.66"},{"key":"S0007125000007315_ref23","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1987.01800190054009"},{"key":"S0007125000007315_ref27","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.159.4.539"},{"key":"S0007125000007315_ref35","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.20297"}],"container-title":["British Journal of Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S0007125000007315","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,25]],"date-time":"2023-05-25T21:09:46Z","timestamp":1685048986000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S0007125000007315\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,7]]},"references-count":38,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2009,7]]}},"alternative-id":["S0007125000007315"],"URL":"https:\/\/doi.org\/10.1192\/bjp.bp.108.061424","relation":{},"ISSN":["0007-1250","1472-1465"],"issn-type":[{"value":"0007-1250","type":"print"},{"value":"1472-1465","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,7]]}}}