{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T16:13:00Z","timestamp":1788883980352,"version":"build-2803163510"},"reference-count":51,"publisher":"American Medical Association (AMA)","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Psychiatry"],"published-print":{"date-parts":[[2024,12,1]]},"abstract":"Importance<\/jats:title>Schizophrenia and bipolar disorder are highly heritable psychiatric disorders with strong genetic and phenotypic overlap. Twin and molecular methods can be leveraged to predict the shared genetic liability to these disorders.<\/jats:p><\/jats:sec>Objective<\/jats:title>To investigate whether twin concordance for psychosis depends on the level of polygenic risk score (PRS) for psychosis and zygosity and compare PRS from cases and controls from several large samples and estimate the twin heritability of psychosis.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>In this case-control study, psychosis PRS were generated from a genome-wide association study (GWAS) combining schizophrenia and bipolar disorder into a single psychosis phenotype and compared between cases and controls from the Schizophrenia and Bipolar Twin Study in Sweden (STAR) project. Further tests were conducted to ascertain if twin concordance for psychosis depended on the mean PRS for psychosis. Structural equation modeling was used to estimate heritability. This study constituted an analysis of existing clinical and population datasets with genotype and\/or twin data. Included were twins from the STAR cohort and from the Swedish Twin Registry. Data were collected during the 2006 to 2013 period and analyzed from March 2023 to June 2024.<\/jats:p><\/jats:sec>Exposures<\/jats:title>PRS for psychosis based on the most recent GWAS of combined schizophrenia\/bipolar disorder.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>Psychosis case status was assessed by clinical interviews and\/or Swedish National Register data.<\/jats:p><\/jats:sec>Results<\/jats:title>The final cohort comprised 87 pairs of twins with 1 or both affected and 59 unaffected pairs from the STAR project (for a total of 292 twins) as well as 443 pairs with 1 or both affected and 20 913 unaffected pairs from the Swedish Twin Registry. Among the 292 twins (mean [SD] birth year, 1960 [10.8] years; 158 female [54.1%]; 134 male [45.9%]), 134 were monozygotic twins, and 158 were dyzygotic twins. PRS for psychosis was higher in cases than in controls and associated with twin concordance for psychosis (1-SD increase in PRS, odds ratio [OR], 2.12; 95% CI,\u20091.23-3.87 on case status in monozygotic twins and OR,\u20092.74; 95% CI,\u20091.56-5.30 in dizygotic twins). The association between PRS for psychosis and concordance was not modified by zygosity. The twin heritability was estimated at 0.73 (95% CI,\u20090.30-1.00), which overlapped with the estimate in the full Swedish Twin Registry (0.69; 95% CI,\u20090.43-0.85).<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>In this case-control study, using the natural experiment of twins, results suggest that twins with greater inherited liability for psychosis were more likely to have an affected co-twin. Results from twin and molecular designs largely aligned. Even as illness vulnerability is not solely genetic, PRS carried predictive power for psychosis even in a modest sample size.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamapsychiatry.2024.2406","type":"journal-article","created":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T15:35:48Z","timestamp":1724859348000},"page":"1246","source":"Crossref","is-referenced-by-count":16,"title":["Polygenic Risk Scores and Twin Concordance for Schizophrenia and Bipolar Disorder"],"prefix":"10.1001","volume":"81","author":[{"given":"Jie","family":"Song","sequence":"first","affiliation":[{"name":"Mental Health Center and West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China"},{"name":"Med-X Center for Informatics, Sichuan University, Chengdu, China"},{"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00eblle A.","family":"Pasman","sequence":"additional","affiliation":[{"name":"Med-X Center for Informatics, Sichuan University, Chengdu, China"},{"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktoria","family":"Johansson","sequence":"additional","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden"},{"name":"Department of Clinical Sciences, Psychiatry, Ume\u00e5 University, Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Kuja-Halkola","sequence":"additional","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arvid","family":"Harder","sequence":"additional","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Karlsson","sequence":"additional","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaarina","family":"Kowalec","sequence":"additional","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden"},{"name":"College of Pharmacy, University of Manitoba, Winnipeg, Manitoba, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy L.","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyrone D.","family":"Cannon","sequence":"additional","affiliation":[{"name":"Department of Psychology, Yale University, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina M.","family":"Hultman","sequence":"additional","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick F.","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden"},{"name":"Departments of Genetics and Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"1","key":"yoi240054r1","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1001\/archpsyc.64.1.19","article-title":"Lifetime prevalence of psychotic and bipolar I disorders in a general population.","volume":"64","author":"Per\u00e4l\u00e4","year":"2007","journal-title":"Arch Gen Psychiatry"},{"issue":"2","key":"yoi240054r2","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/S2215-0366(21)00395-3","article-title":"Global, regional, and national burden of 12 mental disorders in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019.","volume":"9","author":"GBD 2019 Mental Disorders Collaborators","year":"2022","journal-title":"Lancet Psychiatry"},{"issue":"4","key":"yoi240054r3","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1001\/jamapsychiatry.2014.2502","article-title":"Mortality in mental disorders and global disease burden implications: a systematic review and meta-analysis.","volume":"72","author":"Walker","year":"2015","journal-title":"JAMA Psychiatry"},{"issue":"9659","key":"yoi240054r4","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1016\/S0140-6736(09)60072-6","article-title":"Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: a population-based study.","volume":"373","author":"Lichtenstein","year":"2009","journal-title":"Lancet"},{"issue":"1","key":"yoi240054r5","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1093\/schbul\/sbp137","article-title":"Narrowing the boundaries of the genetic architecture of schizophrenia.","volume":"36","author":"Wray","year":"2010","journal-title":"Schizophr Bull"},{"issue":"10","key":"yoi240054r6","doi-asserted-by":"publisher","first-page":"1417","DOI":"10.1017\/S0033291706008385","article-title":"Recurrence risks for schizophrenia in a Swedish national cohort.","volume":"36","author":"Lichtenstein","year":"2006","journal-title":"Psychol Med"},{"issue":"1","key":"yoi240054r7","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1001\/archpsyc.55.1.67","article-title":"The genetic epidemiology of schizophrenia in a Finnish twin cohort: a population-based modeling study.","volume":"55","author":"Cannon","year":"1998","journal-title":"Arch Gen Psychiatry"},{"issue":"3","key":"yoi240054r8","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1093\/schbul\/sbu016","article-title":"Genetic relationships between schizophrenia, bipolar disorder, and schizoaffective disorder.","volume":"40","author":"Cardno","year":"2014","journal-title":"Schizophr Bull"},{"issue":"7","key":"yoi240054r9","doi-asserted-by":"publisher","first-page":"1469","DOI":"10.1016\/j.cell.2019.11.020","article-title":"Genomic relationships, novel loci, and pleiotropic mechanisms across 8 psychiatric disorders.","volume":"179","author":"Cross-Disorder Group of the Psychiatric Genomics Consortium. Electronic address: plee0@mgh.harvard.edu","year":"2019","journal-title":"Cell"},{"issue":"6","key":"yoi240054r10","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1038\/s41588-021-00857-4","article-title":"Genome-wide association study of more than 40 000 bipolar disorder cases provides new insights into the underlying biology.","volume":"53","author":"Mullins","year":"2021","journal-title":"Nat Genet"},{"issue":"7906","key":"yoi240054r11","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1038\/s41586-022-04434-5","article-title":"Mapping genomic loci implicates genes and synaptic biology in schizophrenia.","volume":"604","author":"Trubetskoy","year":"2022","journal-title":"Nature"},{"issue":"7","key":"yoi240054r12","doi-asserted-by":"publisher","first-page":"1705","DOI":"10.1016\/j.cell.2018.05.046","article-title":"Genomic dissection of bipolar disorder and schizophrenia, including 28 subphenotypes.","volume":"173","author":"Ruderfer","year":"2018","journal-title":"Cell"},{"issue":"11","key":"yoi240054r13","doi-asserted-by":"publisher","first-page":"1413","DOI":"10.1176\/ajp.140.11.1413","article-title":"Overview: a current perspective on twin studies of schizophrenia.","volume":"140","author":"Kendler","year":"1983","journal-title":"Am J Psychiatry"},{"issue":"6","key":"yoi240054r14","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1016\/j.biopsych.2017.08.017","article-title":"Heritability of schizophrenia and schizophrenia spectrum based on the nationwide Danish twin register.","volume":"83","author":"Hilker","year":"2018","journal-title":"Biol Psychiatry"},{"issue":"2","key":"yoi240054r15","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1001\/jamapsychiatry.2020.3042","article-title":"Could Polygenic risk scores be useful in psychiatry: a review.","volume":"78","author":"Murray","year":"2021","journal-title":"JAMA Psychiatry"},{"issue":"10","key":"yoi240054r16","doi-asserted-by":"publisher","first-page":"1068","DOI":"10.1111\/jcpp.12295","article-title":"Research review: polygenic methods and their application to psychiatric traits.","volume":"55","author":"Wray","year":"2014","journal-title":"J Child Psychol Psychiatry"},{"issue":"7","key":"yoi240054r17","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1001\/jamapsychiatry.2015.0346","article-title":"Polygenic risk score, parental socioeconomic status, family history of psychiatric disorders, and the risk for schizophrenia: a Danish population-based study and meta-analysis.","volume":"72","author":"Agerbo","year":"2015","journal-title":"JAMA Psychiatry"},{"issue":"9","key":"yoi240054r18","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1038\/mp.2011.34","article-title":"A family-based study of common polygenic variation and risk of schizophrenia.","volume":"16","author":"Ruderfer","year":"2011","journal-title":"Mol Psychiatry"},{"issue":"3","key":"yoi240054r19","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.0020041","article-title":"Assumption-free estimation of heritability from genome-wide identity-by-descent sharing between full siblings.","volume":"2","author":"Visscher","year":"2006","journal-title":"PLoS Genet"},{"key":"yoi240054r20","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/j.schres.2018.08.001","article-title":"The schizophrenia and bipolar twin study in Sweden (STAR).","volume":"204","author":"Johansson","year":"2019","journal-title":"Schizophr Res"},{"issue":"3","key":"yoi240054r21","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1046\/j.1365-2796.2002.01032.x","article-title":"The Swedish Twin Registry: a unique resource for clinical, epidemiological and genetic studies.","volume":"252","author":"Lichtenstein","year":"2002","journal-title":"J Intern Med"},{"key":"yoi240054r22","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1186\/1471-2458-11-450","article-title":"External review and validation of the Swedish national inpatient register.","volume":"11","author":"Ludvigsson","year":"2011","journal-title":"BMC Public Health"},{"issue":"1","key":"yoi240054r26","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.biopsych.2021.02.972","article-title":"Sex-dependent shared and nonshared genetic architecture across mood and psychotic disorders.","volume":"91","author":"Blokland","year":"2022","journal-title":"Biol Psychiatry"},{"issue":"10","key":"yoi240054r27","doi-asserted-by":"publisher","first-page":"1150","DOI":"10.1038\/ng.2742","article-title":"Genome-wide association analysis identifies 13 new risk loci for schizophrenia.","volume":"45","author":"Ripke","year":"2013","journal-title":"Nat Genet"},{"issue":"7510","key":"yoi240054r28","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1038\/nature13595","article-title":"Biological insights from 108 schizophrenia-associated genetic loci.","volume":"511","author":"Schizophrenia Working Group of the Psychiatric Genomics Consortium","year":"2014","journal-title":"Nature"},{"issue":"1","key":"yoi240054r29","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1007\/s10654-010-9521-x","article-title":"LifeGene\u2014a large prospective population-based study of global relevance.","volume":"26","author":"Almqvist","year":"2011","journal-title":"Eur J Epidemiol"},{"issue":"3","key":"yoi240054r30","doi-asserted-by":"publisher","first-page":"930","DOI":"10.1093\/bioinformatics\/btz633","article-title":"RICOPILI: rapid imputation for Consortias Pipeline.","volume":"36","author":"Lam","year":"2020","journal-title":"Bioinformatics"},{"issue":"7571","key":"yoi240054r31","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1038\/nature15393","article-title":"A global reference for human genetic variation.","volume":"526","author":"Auton","year":"2015","journal-title":"Nature"},{"issue":"3","key":"yoi240054r32","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1086\/519795","article-title":"PLINK: a tool set for whole-genome association and population-based linkage analyses.","volume":"81","author":"Purcell","year":"2007","journal-title":"Am J Hum Genet"},{"issue":"10","key":"yoi240054r33","doi-asserted-by":"publisher","first-page":"1279","DOI":"10.1038\/ng.3643","article-title":"A reference panel of 64?976 haplotypes for genotype imputation.","volume":"48","author":"McCarthy","year":"2016","journal-title":"Nat Genet"},{"key":"yoi240054r34","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1186\/1471-2105-9-540","article-title":"Shape-IT: new rapid and accurate algorithm for haplotype inference.","volume":"9","author":"Delaneau","year":"2008","journal-title":"BMC Bioinformatics"},{"issue":"9","key":"yoi240054r35","doi-asserted-by":"publisher","first-page":"1266","DOI":"10.1093\/bioinformatics\/btu014","article-title":"Efficient haplotype matching and storage using the positional Burrows-Wheeler transform (PBWT).","volume":"30","author":"Durbin","year":"2014","journal-title":"Bioinformatics"},{"issue":"1","key":"yoi240054r36","doi-asserted-by":"publisher","first-page":"5086","DOI":"10.1038\/s41467-019-12653-0","article-title":"Improved polygenic prediction by Bayesian multiple regression on summary statistics.","volume":"10","author":"Lloyd-Jones","year":"2019","journal-title":"Nat Commun"},{"issue":"5","key":"yoi240054r37","doi-asserted-by":"publisher","first-page":"746","DOI":"10.1038\/s41588-018-0101-4","article-title":"Signatures of negative selection in the genetic architecture of human complex traits.","volume":"50","author":"Zeng","year":"2018","journal-title":"Nat Genet"},{"key":"yoi240054r38","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/s13742-015-0047-8","article-title":"Second-generation PLINK: rising to the challenge of larger and richer datasets.","volume":"4","author":"Chang","year":"2015","journal-title":"Gigascience"},{"issue":"7","key":"yoi240054r39","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz068","article-title":"EnsembleCNV: an ensemble machine learning algorithm to identify and genotype copy number variation using SNP array data.","volume":"47","author":"Zhang","year":"2019","journal-title":"Nucleic Acids Res"},{"issue":"Database issue","key":"yoi240054r40","doi-asserted-by":"publisher","first-page":"D993","DOI":"10.1093\/nar\/gkt937","article-title":"DECIPHER: database for the interpretation of phenotype-linked plausibly pathogenic sequence and copy-number variation.","volume":"42","author":"Bragin","year":"2014","journal-title":"Nucleic Acids Res"},{"issue":"7483","key":"yoi240054r41","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1038\/nature12818","article-title":"CNVs conferring risk of autism or schizophrenia affect cognition in controls.","volume":"505","author":"Stefansson","year":"2014","journal-title":"Nature"},{"issue":"1","key":"yoi240054r42","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1038\/ng.3725","article-title":"Contribution of copy number variants to schizophrenia from a genome-wide study of 41?321 subjects.","volume":"49","author":"Marshall","year":"2017","journal-title":"Nat Genet"},{"issue":"10","key":"yoi240054r43","doi-asserted-by":"publisher","first-page":"1063","DOI":"10.1038\/ng.3092","article-title":"Refining analyses of copy number variation identifies specific genes associated with developmental delay.","volume":"46","author":"Coe","year":"2014","journal-title":"Nat Genet"},{"issue":"12","key":"yoi240054r44","doi-asserted-by":"publisher","first-page":"1187","DOI":"10.1001\/archpsyc.60.12.1187","article-title":"Schizophrenia as a complex trait: evidence from a meta-analysis of twin studies.","volume":"60","author":"Sullivan","year":"2003","journal-title":"Arch Gen Psychiatry"},{"issue":"3","key":"yoi240054r45","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1023\/A:1016025229858","article-title":"Evaluation of analyses of univariate discrete twin data.","volume":"32","author":"Sullivan","year":"2002","journal-title":"Behav Genet"},{"issue":"2","key":"yoi240054r47","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1111\/bdi.12242","article-title":"Bipolar disorder and its relation to major psychiatric disorders: a family-based study in the Swedish population.","volume":"17","author":"Song","year":"2015","journal-title":"Bipolar Disord"},{"issue":"11","key":"yoi240054r48","doi-asserted-by":"publisher","first-page":"2773","DOI":"10.1002\/art.38097","article-title":"Familial risks and heritability of rheumatoid arthritis: role of rheumatoid factor\/anticitrullinated protein antibody status, number and type of affected relatives, sex, and age.","volume":"65","author":"Frisell","year":"2013","journal-title":"Arthritis Rheum"},{"issue":"11","key":"yoi240054r49","doi-asserted-by":"publisher","first-page":"1461","DOI":"10.1136\/annrheumdis-2021-219914","article-title":"Familial aggregation and heritability: a nationwide family-based study of idiopathic inflammatory myopathies.","volume":"80","author":"Che","year":"2021","journal-title":"Ann Rheum Dis"},{"issue":"7256","key":"yoi240054r50","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1038\/nature08185","article-title":"Common polygenic variation contributes to risk of schizophrenia and bipolar disorder.","volume":"460","author":"Purcell","year":"2009","journal-title":"Nature"},{"issue":"13","key":"yoi240054r51","doi-asserted-by":"publisher","first-page":"2235","DOI":"10.1002\/sim.5645","article-title":"A goodness-of-fit test for the proportional odds regression model.","volume":"32","author":"Fagerland","year":"2013","journal-title":"Stat Med"},{"key":"yoi240054r23","volume-title":"Structured Clinical Interview for DSM-IV Axis I Disorders, Clinician Version (SCID-CV)","author":"First","year":"1996"},{"key":"yoi240054r24","volume-title":"Structured Clinical Interview for DSM-IV Axis II Personality Disorders, (SCID-II)","author":"First","year":"1997"},{"key":"yoi240054r25","volume-title":"Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Research Version, Patient Edition. (SCID-I\/P)","author":"First","year":"2002"},{"key":"yoi240054r46","author":"Boker","year":"2012"}],"container-title":["JAMA Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamapsychiatry\/articlepdf\/2822688\/jamapsychiatry_song_2024_oi_240054_1733254039.81338.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T16:01:31Z","timestamp":1733328091000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamapsychiatry\/fullarticle\/2822688"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,1]]},"references-count":51,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2024,12,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamapsychiatry.2024.2406","relation":{},"ISSN":["2168-622X"],"issn-type":[{"value":"2168-622X","type":"print"}],"subject":[],"published":{"date-parts":[[2024,12,1]]}}}