{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T20:32:53Z","timestamp":1793392373642,"version":"4.5.0"},"reference-count":58,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,3,27]],"date-time":"2025-03-27T00:00:00Z","timestamp":1743033600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,3,27]],"date-time":"2025-03-27T00:00:00Z","timestamp":1743033600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2018-01322"],"award-info":[{"award-number":["2018-01322"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004472","name":"Riksbankens Jubileumsfond","doi-asserted-by":"publisher","award":["P20-0125"],"award-info":[{"award-number":["P20-0125"]}],"id":[{"id":"10.13039\/501100004472","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Transl Psychiatry"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Anxiety and depression commonly occur together resulting in worse health outcomes than when they occur in isolation. We aimed to determine whether the genetic liability for comorbid anxiety and depression was greater than when anxiety or depression occurred alone. Data from 12,792 genotyped twins (ages 38\u201385) were analysed, including 1,986 complete monozygotic and 1,594 complete dizygotic pairs. Outcomes were prescription of antidepressant and anxiolytic drugs, as defined by the World Health Organization Anatomical Therapeutic Chemical Classification System (ATC) convention, for comorbid anxiety and depression (<jats:italic>n<\/jats:italic>\u2009=\u20091028), anxiety only (<jats:italic>n<\/jats:italic>\u2009=\u2009718), and depression only (<jats:italic>n<\/jats:italic>\u2009=\u2009484). Heritability of each outcome was estimated using twin modelling, and the influence of common genetic variation was assessed from polygenic scores (PGS) for depressive symptoms, anxiety, and 40 other traits. Heritability of comorbid anxiety and depression was 79% compared with 41% for anxiety and 50% for depression alone. The PGS for depressive symptoms likewise predicted more variation in comorbid anxiety and depression (adjusted odds ratio per <jats:italic>SD<\/jats:italic> PGS\u2009=\u20091.53, 95% CI\u2009=\u20091.43\u20131.63; \u0394<jats:italic>R<\/jats:italic>\n            <jats:sup>2<\/jats:sup>\u2009=\u20090.031, \u0394AUC = 0.044) than the other outcomes, with nearly identical results when comorbid anxiety and depression was defined by International Classification of Diseases (ICD) diagnoses (adjusted odds ratio per <jats:italic>SD<\/jats:italic> PGS\u2009=\u20091.70, 95% CI\u2009=\u20091.53\u20131.90; \u0394<jats:italic>R<\/jats:italic>\n            <jats:sup>2<\/jats:sup>\u2009=\u20090.036, \u0394AUC = 0.051). Individuals in the highest decile of PGS for depressive symptoms had over 5 times higher odds of being prescribed medication for comorbid anxiety and depression compared to those in the lowest decile. While results on a predominant role of depressive symptoms may have been biased by the size and heterogeneity of available data bases, they are consistent with the conclusion that genetic factors explain substantially more variation in comorbid anxiety and depression than anxiety or depression alone.<\/jats:p>","DOI":"10.1038\/s41398-025-03325-3","type":"journal-article","created":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T23:53:47Z","timestamp":1743033227000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Heritability and polygenic load for comorbid anxiety and depression"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4009-0090","authenticated-orcid":false,"given":"Fara","family":"Tabrizi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rgen","family":"Ros\u00e9n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hampus","family":"Gr\u00f6nvall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor Rahimzadeh","family":"William-Olsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Arner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7315-7899","authenticated-orcid":false,"given":"Patrik KE","family":"Magnusson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"Palm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6851-3297","authenticated-orcid":false,"given":"Henrik","family":"Larsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2141-2816","authenticated-orcid":false,"given":"Alexander","family":"Viktorin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Bernhardsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Bj\u00f6rkdahl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Billy","family":"Jansson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d6rjan","family":"Sundin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0096-9765","authenticated-orcid":false,"given":"Doug","family":"Speed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fredrik","family":"\u00c5hs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,27]]},"reference":[{"key":"3325_CR1","doi-asserted-by":"publisher","first-page":"327","DOI":"10.31887\/DCNS.2015.17.3\/bbandelow","volume":"17","author":"B Bandelow","year":"2015","unstructured":"Bandelow B, Michaelis S. Epidemiology of anxiety disorders in the 21st century. Dialogues Clin Neurosci. 2015;17:327\u201335.","journal-title":"Dialogues Clin Neurosci"},{"key":"3325_CR2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-018-21243-x","volume":"8","author":"GY Lim","year":"2018","unstructured":"Lim GY, Tam WW, Lu Y, Ho CS, Zhang MW, Ho RC. Prevalence of depression in the community from 30 Countries between 1994 and 2014 \/692\/699\/476\/1414 \/692\/499 article. Sci Rep. 2018;8:1\u201310.","journal-title":"Sci Rep"},{"key":"3325_CR3","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1017\/S0033291707002012","volume":"38","author":"RC Kessler","year":"2008","unstructured":"Kessler RC, Gruber M, Hettema JM, Hwang I, Sampson N, Yonkers KA. Co-morbid major depression and generalized anxiety disorders in the National Comorbidity Survey follow-up. Psychol Med. 2008;38:365\u201374.","journal-title":"Psychol Med"},{"key":"3325_CR4","first-page":"244","volume":"3","author":"RMA Hirschfeld","year":"2001","unstructured":"Hirschfeld RMA. The comorbidity of major depression and anxiety disorders: Recognition and management in primary care. Prim Care Companion J Clin Psychiatry. 2001;3:244\u201354.","journal-title":"Prim Care Companion J Clin Psychiatry"},{"key":"3325_CR5","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1146\/annurev.psych.49.1.377","volume":"49","author":"S Mineka","year":"1998","unstructured":"Mineka S, Watson D, Clark LA. Comorbidity of anxiety and unipolar mood disorders. Annu Rev Psychol. 1998;49:377\u2013412.","journal-title":"Annu Rev Psychol"},{"key":"3325_CR6","doi-asserted-by":"publisher","first-page":"1734","DOI":"10.1176\/ajp.154.12.1734","volume":"154","author":"M Olfson","year":"1997","unstructured":"Olfson M, Fireman B, Weissman MM, Leon AC, Sheehan D, Kathol RG, et al. Mental disorders and disability among patients in a primary care group practice. Am J Psychiatry. 1997;154:1734\u201340.","journal-title":"Am J Psychiatry"},{"key":"3325_CR7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jpsychires.2017.02.020","volume":"91","author":"M Dold","year":"2017","unstructured":"Dold M, Bartova L, Souery D, Mendlewicz J, Serretti A, Porcelli S, et al. Clinical characteristics and treatment outcomes of patients with major depressive disorder and comorbid anxiety disorders - results from a European multicenter study. J Psychiatr Res. 2017;91:1\u201313.","journal-title":"J Psychiatr Res"},{"key":"3325_CR8","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1176\/appi.ajp.2007.06111868","volume":"165","author":"M Fava","year":"2008","unstructured":"Fava M, Rush AJ, Alpert JE, Ph D, Balasubramani GK, Ph D, et al. Difference in treatment outcome in outpatients with anxious versus nonanxious depression: A STAR * D report. Am J Psychiatry. 2008;165:342\u201351.","journal-title":"Am J Psychiatry"},{"key":"3325_CR9","doi-asserted-by":"publisher","first-page":"28","DOI":"10.5694\/mjao12.10628","volume":"1","author":"JWG Tiller","year":"2012","unstructured":"Tiller JWG. Depression and anxiety. Med J Aust. 2012;1:28\u201332.","journal-title":"Med J Aust"},{"key":"3325_CR10","first-page":"198","volume-title":"Depression and Anxiety","author":"E Jakubovski","year":"2019","unstructured":"Jakubovski E, Johnson JA, Nasir M, M\u00fcller-Vahl K, Bloch MH. Systematic review and meta-analysis: dose\u2013response curve of SSRIs and SNRIs in anxiety disorders. Depression and Anxiety. 36. Blackwell Publishing Inc; 2019. p. 198\u2013212."},{"key":"3325_CR11","first-page":"459","volume-title":"Journal of Psychopharmacology","author":"A Cleare","year":"2015","unstructured":"Cleare A, Pariante CM, Young AH, Anderson IM, Christmas D, Cowen PJ, et al. Evidence-based guidelines for treating depressive disorders with antidepressants: a revision of the 2008 British Association for Psychopharmacology guidelines. Journal of Psychopharmacology. 29. SAGE Publications Ltd; 2015. p. 459\u2013525."},{"key":"3325_CR12","doi-asserted-by":"publisher","first-page":"2217","DOI":"10.1017\/S0033291721000441","volume":"51","author":"KM Kendall","year":"2021","unstructured":"Kendall KM, Van Assche E, Andlauer TFM, Choi KW, Luykx JJ, Schulte EC, et al. The genetic basis of major depression. Psychol Med. 2021;51:2217\u201330.","journal-title":"Psychol Med"},{"key":"3325_CR13","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1038\/npp.2015.266","volume":"41","author":"JW Smoller","year":"2016","unstructured":"Smoller JW. The genetics of stress-related disorders: PTSD, depression, and anxiety disorders. Neuropsychopharmacology. 2016;41:297\u2013319.","journal-title":"Neuropsychopharmacology"},{"key":"3325_CR14","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1017\/S003329170400412X","volume":"35","author":"CM Middeldorp","year":"2005","unstructured":"Middeldorp CM, Cath DC, Van Dyck R, Boomsma DI. The co-morbidity of anxiety and depression in the perspective of genetic epidemiology. A review of twin and family studies. Psychol Med. 2005;35:611\u201324.","journal-title":"Psychol Med"},{"key":"3325_CR15","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1002\/ajmg.c.30171","volume":"148","author":"JM Hettema","year":"2008","unstructured":"Hettema JM. What is the genetic relationship between anxiety and depression? Am J Med Genet, Part C: Semin Med Genet. 2008;148:140\u20136.","journal-title":"Am J Med Genet, Part C: Semin Med Genet"},{"key":"3325_CR16","doi-asserted-by":"publisher","first-page":"1072","DOI":"10.1002\/ajmg.b.32477","volume":"171","author":"G Guffanti","year":"2016","unstructured":"Guffanti G, Gameroff MJ, Warner V, Talati A, Glatt CE, Wickramaratne P, et al. Heritability of major depressive and comorbid anxiety disorders in multi-generational families at high risk for depression. Am J Med Genet, Part B: Neuropsychiatr Genet. 2016;171:1072\u20139.","journal-title":"Am J Med Genet, Part B: Neuropsychiatr Genet"},{"key":"3325_CR17","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1038\/s41576-018-0018-x","volume":"19","author":"A Torkamani","year":"2018","unstructured":"Torkamani A, Wineinger NE, Topol EJ. The personal and clinical utility of polygenic risk scores. Nat Rev Genet. 2018;19:581\u201390.","journal-title":"Nat Rev Genet"},{"key":"3325_CR18","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1176\/appi.ajp.2019.19030256","volume":"177","author":"DF Levey","year":"2020","unstructured":"Levey DF, Gelernter J, Polimanti R, Zhou H, Cheng Z, Aslan M, et al. Reproducible genetic risk loci for anxiety: results from \u223c200,000 participants in the million veteran program. Am J Psychiatry. 2020;177:223\u201332.","journal-title":"Am J Psychiatry"},{"key":"3325_CR19","doi-asserted-by":"publisher","first-page":"3292","DOI":"10.1038\/s41380-019-0559-1","volume":"25","author":"KL Purves","year":"2020","unstructured":"Purves KL, Coleman JRI, Meier SM, Rayner C, Davis KAS, Cheesman R, et al. A major role for common genetic variation in anxiety disorders. Mol Psychiatry. 2020;25:3292\u2013303.","journal-title":"Mol Psychiatry"},{"key":"3325_CR20","unstructured":"Strom NI, Verhulst B, Bacanu SA, Cheesman R, Purves KL, Gedik H, et al. Genome-wide association study of major anxiety disorders in 122,341 European-ancestry cases identifies 58 loci and highlights GABAergic signaling. medRxiv. [Preprint].[2024 Jul 5]; https:\/\/www.medrxiv.org\/content\/10.1101\/2024.07.03.24309466v1."},{"key":"3325_CR21","doi-asserted-by":"publisher","first-page":"2036","DOI":"10.1038\/s41588-024-01908-2","volume":"56","author":"E Friligkou","year":"2024","unstructured":"Friligkou E, L\u00f8khammer S, Cabrera-Mendoza B, Shen J, He J, Deiana G, et al. Gene discovery and biological insights into anxiety disorders from a large-scale multi-ancestry genome-wide association study. Nat Genet. 2024;56:2036\u201345.","journal-title":"Nat Genet"},{"key":"3325_CR22","doi-asserted-by":"publisher","unstructured":"Cai N, Revez JA, Adams MJ, Andlauer TFM, Breen G, Byrne EM, et al. Minimal phenotyping yields genome-wide association signals of low specificity for major depression. Nat Genet. https:\/\/doi.org\/10.1038\/s41588-020-0594-5.","DOI":"10.1038\/s41588-020-0594-5"},{"key":"3325_CR23","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1038\/s41588-018-0090-3","volume":"50","author":"NR Wray","year":"2018","unstructured":"Wray NR, Ripke S, Mattheisen M, Trzaskowski M, Byrne EM, Abdellaoui A, et al. Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression. Nat Genet. 2018;50:668\u201381.","journal-title":"Nat Genet"},{"key":"3325_CR24","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1016\/j.jad.2022.11.051","volume":"323","author":"MR Davies","year":"2023","unstructured":"Davies MR, Glen K, Mundy J, ter Kuile AR, Adey BN, Armour C, et al. Factors associated with anxiety disorder comorbidity. J Affect Disord. 2023;323:280\u201391.","journal-title":"J Affect Disord"},{"key":"3325_CR25","doi-asserted-by":"publisher","first-page":"1152","DOI":"10.1001\/jamapsychiatry.2021.1988","volume":"78","author":"BL Mitchell","year":"2021","unstructured":"Mitchell BL, Thorp JG, Wu Y, Campos AI, Nyholt DR, Gordon SD, et al. Polygenic risk scores derived from varying definitions of depression and risk of depression. JAMA Psychiatry. 2021;78:1152\u201360.","journal-title":"JAMA Psychiatry"},{"key":"3325_CR26","doi-asserted-by":"publisher","first-page":"1832","DOI":"10.1038\/s41591-023-02352-1","volume":"29","author":"TD Als","year":"2023","unstructured":"Als TD, Kurki MI, Grove J, Voloudakis G, Therrien K, Tasanko E, et al. Depression pathophysiology, risk prediction of recurrence and comorbid psychiatric disorders using genome-wide analyses. Nat Med. 2023;29:1832\u201344.","journal-title":"Nat Med"},{"key":"3325_CR27","doi-asserted-by":"publisher","first-page":"7368","DOI":"10.1017\/S0033291723000983","volume":"53","author":"BJ Coombes","year":"2023","unstructured":"Coombes BJ, Landi I, Choi KW, Singh K, Fennessy B, Jenkins GD, et al. The genetic contribution to the comorbidity of depression and anxiety: a multi-site electronic health records study of almost 178 000 people. Psychol Med. 2023;53:7368\u201374.","journal-title":"Psychol Med"},{"key":"3325_CR28","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1370\/afm.983","volume":"7","author":"JM Valderas","year":"2009","unstructured":"Valderas JM, Starfield B, Sibbald B, Salisbury C, Roland M. Defining comorbidity: Implications for understanding health and health services. Ann Fam Med. 2009;7:357\u201363.","journal-title":"Ann Fam Med"},{"key":"3325_CR29","doi-asserted-by":"publisher","first-page":"1744","DOI":"10.1038\/s41562-021-01119-3","volume":"5","author":"J Becker","year":"2021","unstructured":"Becker J, Burik CAP, Goldman G, Wang N, Jayashankar H, Bennett M, et al. Resource profile and user guide of the Polygenic Index Repository. Nat Hum Behav. 2021;5:1744\u201358.","journal-title":"Nat Hum Behav"},{"key":"3325_CR30","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1375\/twin.9.6.875","volume":"9","author":"P Lichtenstein","year":"2006","unstructured":"Lichtenstein P, Sullivan PF, Cnattingius S, Gatz M, Johansson S, Carlstr\u00f6m E, et al. The Swedish Twin Registry in the third millennium: an update. Twin Res Hum Genet. 2006;9:875\u201382.","journal-title":"Twin Res Hum Genet"},{"key":"3325_CR31","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1017\/thg.2019.99","volume":"22","author":"U Zagai","year":"2019","unstructured":"Zagai U, Lichtenstein P, Pedersen NL, Magnusson PKE. The Swedish Twin Registry: Content and Management as a Research Infrastructure. Twin Res Hum Genet. 2019;22:672\u201380.","journal-title":"Twin Res Hum Genet"},{"key":"3325_CR32","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1007\/s10508-012-9947-1","volume":"42","author":"KL Donahue","year":"2013","unstructured":"Donahue KL, D\u2019Onofrio BM, Lichtenstein P, L\u00e5ngstr\u00f6m N. Testing putative causal associations of risk factors for early intercourse in the study of twin adults: genes and environment (STAGE). Arch Sex Behav. 2013;42:35\u201344.","journal-title":"Arch Sex Behav"},{"key":"3325_CR33","unstructured":"Socialstyrelsen. National Prescribed Drug Register. 2020 [cited 2023 Feb 27]. Socialstyrelsen. Available from: https:\/\/www.socialstyrelsen.se\/en\/statistics-and-data\/registers\/national-prescribed-drug-register\/."},{"key":"3325_CR34","unstructured":"WHO. WHO. Collaborating Centre for Drug Statistics Methodology [Internet]. 2021 [cited 2023 Feb 27]; Available from: https:\/\/www.whocc.no\/."},{"key":"3325_CR35","unstructured":"Socialstyrelsen. Utv\u00e4rdering av v\u00e5rd vid depression och \u00e5ngestsyndrom [Internet]. Stockholm; 2019. Available from: www.socialstyrelsen.se."},{"key":"3325_CR36","unstructured":"UK Biobank. Vol. 7, Protocol No: UKBB-PROT-09-06.PROT-09-06. 2007. p. 1\u2013112 UK Biobank: Protocol for a large-scale prospective epidemiological resource. Available from: http:\/\/www.ukbiobank.ac.uk\/wp-content\/uploads\/2011\/11\/UK-Biobank-Protocol.pdf."},{"key":"3325_CR37","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1038\/s41593-018-0326-7","volume":"22","author":"DM Howard","year":"2019","unstructured":"Howard DM, Adams MJ, Clarke TK, Hafferty JD, Gibson J, Shirali M, et al. Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions. Nat Neurosci. 2019;22:343\u201352.","journal-title":"Nat Neurosci"},{"key":"3325_CR38","doi-asserted-by":"crossref","unstructured":"Trubetskoy V, Pardi\u00f1as AF, Qi T, Panagiotaropoulou G, Awasthi S, Bigdeli TB, et al. Mapping genomic loci implicates genes and synaptic biology in schizophrenia. Nature. 2022;604:502\u20138.","DOI":"10.1038\/s41586-022-04434-5"},{"key":"3325_CR39","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pmed.1001779","volume":"12","author":"C Sudlow","year":"2015","unstructured":"Sudlow C, Gallacher J, Allen N, Beral V, Burton P, Danesh J, et al. UK Biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age. PLoS Med. 2015;12:1\u201310.","journal-title":"PLoS Med"},{"key":"3325_CR40","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1038\/s41588-020-0600-y","volume":"52","author":"D Speed","year":"2020","unstructured":"Speed D, Holmes J, Balding DJ. Evaluating and improving heritability models using summary statistics. Nat Genet. 2020;52:458\u201362.","journal-title":"Nat Genet"},{"key":"3325_CR41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-020-20314-w","volume":"12","author":"Q Zhang","year":"2021","unstructured":"Zhang Q, Priv\u00e9 F, Vilhj\u00e1lmsson B, Speed D. Improved genetic prediction of complex traits from individual-level data or summary statistics. Nat Commun. 2021;12:1\u20139.","journal-title":"Nat Commun"},{"key":"3325_CR42","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1111\/j.1469-1809.1965.tb00500.x","volume":"29","author":"DS Falconer","year":"1965","unstructured":"Falconer DS. The inheritance of liability to certain diseases, estimated from the incidence among relatives. Ann Hum Genet. 1965;29:51\u201376.","journal-title":"Ann Hum Genet"},{"key":"3325_CR43","volume-title":"Methodology for Genetic Studies of Twins and Families","author":"MC Neale","year":"2004","unstructured":"Neale MC, Maes HH. Methodology for Genetic Studies of Twins and Families. Dordrecht: Kluwer Academics; 2004."},{"key":"3325_CR44","unstructured":"Holst KK, Scheike T mets (R package). Version 0.2.8. URL: http:\/\/cran.r-project.org\/web\/packages\/mets\/."},{"key":"3325_CR45","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","volume":"57","author":"Y Benjamini","year":"1995","unstructured":"Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Society: Ser B. 1995;57:289\u2013300.","journal-title":"J R Stat Society: Ser B"},{"key":"3325_CR46","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1016\/j.biopsych.2017.08.017","volume":"83","author":"R Hilker","year":"2018","unstructured":"Hilker R, Helenius D, Fagerlund B, Skytthe A, Christensen K, Werge TM, et al. Heritability of schizophrenia and schizophrenia spectrum based on the nationwide danish twin register. Biol Psychiatry. 2018;83:492\u20138.","journal-title":"Biol Psychiatry"},{"key":"3325_CR47","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1038\/s41380-019-0634-7","volume":"25","author":"FJA Gordovez","year":"2020","unstructured":"Gordovez FJA, McMahon FJ. The genetics of bipolar disorder. Mol Psychiatry. 2020;25:544\u201359.","journal-title":"Mol Psychiatry"},{"key":"3325_CR48","doi-asserted-by":"publisher","first-page":"1667","DOI":"10.1038\/s41380-021-01413-6","volume":"27","author":"TD Nguyen","year":"2022","unstructured":"Nguyen TD, Harder A, Xiong Y, Kowalec K, H\u00e4gg S, Cai N, et al. Genetic heterogeneity and subtypes of major depression. Mol Psychiatry. 2022;27:1667\u201375.","journal-title":"Mol Psychiatry"},{"key":"3325_CR49","doi-asserted-by":"publisher","first-page":"1469","DOI":"10.1016\/j.cell.2019.11.020","volume":"179","author":"PH Lee","year":"2019","unstructured":"Lee PH, Anttila V, Won H, Feng YCA, Rosenthal J, Zhu Z, et al. Genomic relationships, novel loci, and pleiotropic mechanisms across eight psychiatric disorders. Cell. 2019;179:1469\u20131482.e11.","journal-title":"Cell"},{"key":"3325_CR50","doi-asserted-by":"publisher","first-page":"eaap8757","DOI":"10.1126\/science.aap8757","volume":"360","author":"V Anttila","year":"2018","unstructured":"Anttila V, Bulik-Sullivan B, Finucane HK, Walters RK, Bras J, Duncan L, et al. Analysis of shared heritability in common disorders of the brain. Science. 2018;360:eaap8757.","journal-title":"Science"},{"key":"3325_CR51","first-page":"119","volume":"2","author":"A Caspi","year":"2014","unstructured":"Caspi A, Houts RM, Belsky DW, Goldman-Mellor SJ, Harrington H, Israel S, et al. The p factor: One general psychopathology factor in the structure of psychiatric disorders? Clinical. Psychological Sci. 2014;2:119\u201337.","journal-title":"Psychological Sci"},{"key":"3325_CR52","doi-asserted-by":"crossref","unstructured":"Waszczuk MA, Eaton NR, Krueger RF, Shackman AJ, Waldman ID, Zald DH, et al. Redefining phenotypes to advance psychiatric genetics: Implications from hierarchical taxonomy of psychopathology. J Abnorm Psychol. 2020;129:143\u201361.","DOI":"10.1037\/abn0000486"},{"key":"3325_CR53","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1007\/s10979-005-6832-7","volume":"29","author":"ME Rice","year":"2005","unstructured":"Rice ME, Harris GT. Comparing effect sizes in follow-up studies: ROC area, Cohen\u2019s d, and r. Law Hum Behav. 2005;29:615\u201320.","journal-title":"Law Hum Behav"},{"key":"3325_CR54","doi-asserted-by":"publisher","first-page":"e356","DOI":"10.1016\/S2468-2667(17)30118-4","volume":"2","author":"K Hughes","year":"2017","unstructured":"Hughes K, Bellis MA, Hardcastle KA, Sethi D, Butchart A, Mikton C, et al. The effect of multiple adverse childhood experiences on health: a systematic review and meta-analysis. Lancet Public Health. 2017;2:e356\u201366.","journal-title":"Lancet Public Health"},{"key":"3325_CR55","doi-asserted-by":"publisher","first-page":"1103","DOI":"10.1111\/jcpp.12621","volume":"57","author":"A Reuben","year":"2016","unstructured":"Reuben A, Moffitt TE, Caspi A, Belsky DW, Harrington H, Schroeder F, et al. Lest we forget: comparing retrospective and prospective assessments of adverse childhood experiences in the prediction of adult health. J Child Psychol Psychiatry. 2016;57:1103\u201312.","journal-title":"J Child Psychol Psychiatry"},{"key":"3325_CR56","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/S0749-3797(98)00017-8","volume":"14","author":"VJ Felitti","year":"1998","unstructured":"Felitti VJ, Anda RF, Nordenberg D, Williamson DF, Spitz AM, Edwards V, et al. Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults: the adverse childhood experiences (ACE) study. Am J Prev Med. 1998;14:245\u201358.","journal-title":"Am J Prev Med"},{"key":"3325_CR57","unstructured":"Centers for Disease Control and Prevention. https:\/\/www.cdc.gov\/violenceprevention\/aces\/ace-brfss.html. 2024. Behavioral Risk Factor Surveillance System Survey ACE Data, 2009\u20132021."},{"key":"3325_CR58","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1001\/jamapediatrics.2020.5602","volume":"175","author":"JR Baldwin","year":"2021","unstructured":"Baldwin JR, Caspi A, Meehan AJ, Ambler A, Arseneault L, Fisher HL, et al. Population vs individual prediction of poor health from results of adverse childhood experiences screening. JAMA Pediatr. 2021;175:385\u201393.","journal-title":"JAMA Pediatr"}],"container-title":["Translational Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41398-025-03325-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41398-025-03325-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41398-025-03325-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T09:28:40Z","timestamp":1743326920000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41398-025-03325-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,27]]},"references-count":58,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["3325"],"URL":"https:\/\/doi.org\/10.1038\/s41398-025-03325-3","relation":{},"ISSN":["2158-3188"],"issn-type":[{"value":"2158-3188","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,27]]},"assertion":[{"value":"15 February 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 February 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 March 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 March 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"98"}}