{"entity": "journal", "iuid": "a9c3bf8345114a30b4a027c431bdede5", "timestamp": "2026-07-20T01:39:02.389Z", "links": {"self": {"href": "https://publications.scilifelab.se/journal/JAMA%20Psychiatry.json"}, "display": {"href": "https://publications.scilifelab.se/journal/JAMA%20Psychiatry"}}, "title": "JAMA Psychiatry", "issn": "2168-6238", "issn-l": "2168-622X", "publications_count": 5, "publications": [{"entity": "publication", "iuid": "80a12b9f6cde4b0f81b779dbcdbf29ad", "links": {"self": {"href": "https://publications.scilifelab.se/publication/80a12b9f6cde4b0f81b779dbcdbf29ad.json"}, "display": {"href": "https://publications.scilifelab.se/publication/80a12b9f6cde4b0f81b779dbcdbf29ad"}}, "title": "Polygenic Risk Scores and Twin Concordance for Schizophrenia and Bipolar Disorder.", "authors": [{"family": "Song", "given": "Jie", "initials": "J"}, {"family": "Pasman", "given": "Jo\u00eblle A", "initials": "JA"}, {"family": "Johansson", "given": "Viktoria", "initials": "V"}, {"family": "Kuja-Halkola", "given": "Ralf", "initials": "R"}, {"family": "Harder", "given": "Arvid", "initials": "A"}, {"family": "Karlsson", "given": "Robert", "initials": "R"}, {"family": "Lu", "given": "Yi", "initials": "Y"}, {"family": "Kowalec", "given": "Kaarina", "initials": "K"}, {"family": "Pedersen", "given": "Nancy L", "initials": "NL"}, {"family": "Cannon", "given": "Tyrone D", "initials": "TD"}, {"family": "Hultman", "given": "Christina M", "initials": "CM"}, {"family": "Sullivan", "given": "Patrick F", "initials": "PF"}], "type": "journal article", "published": "2024-08-28", "journal": {"title": "JAMA Psychiatry", "issn": "2168-6238", "issn-l": "2168-622X"}, "abstract": "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.\n\nTo 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.\n\nIn 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.\n\nPRS for psychosis based on the most recent GWAS of combined schizophrenia/bipolar disorder.\n\nPsychosis case status was assessed by clinical interviews and/or Swedish National Register data.\n\nThe 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, 1.23-3.87 on case status in monozygotic twins and OR, 2.74; 95% CI, 1.56-5.30 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, 0.30-1.00), which overlapped with the estimate in the full Swedish Twin Registry (0.69; 95% CI, 0.43-0.85).\n\nIn 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.", "doi": "10.1001/jamapsychiatry.2024.2406", "pmid": "39196586", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "NGI SNP genotyping": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11359115"}, {"db": "pii", "key": "2822688"}], "notes": [], "created": "2024-10-21T11:14:59.762Z", "modified": "2024-10-21T11:14:59.771Z"}, {"entity": "publication", "iuid": "b71fefd3189648368056856a895f0346", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b71fefd3189648368056856a895f0346.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b71fefd3189648368056856a895f0346"}}, "title": "Genetic Associations Between Childhood Psychopathology and Adult Depression and Associated Traits in 42 998 Individuals: A Meta-analysis.", "authors": [{"family": "Akingbuwa", "given": "Wonuola A", "initials": "WA"}, {"family": "Hammerschlag", "given": "Anke R", "initials": "AR"}, {"family": "Jami", "given": "Eshim S", "initials": "ES"}, {"family": "Allegrini", "given": "Andrea G", "initials": "AG"}, {"family": "Karhunen", "given": "Ville", "initials": "V"}, {"family": "Sallis", "given": "Hannah", "initials": "H"}, {"family": "Ask", "given": "Helga", "initials": "H"}, {"family": "Askeland", "given": "Ragna B", "initials": "RB"}, {"family": "Baselmans", "given": "Bart", "initials": "B"}, {"family": "Diemer", "given": "Elizabeth", "initials": "E"}, {"family": "Hagenbeek", "given": "Fiona A", "initials": "FA"}, {"family": "Havdahl", "given": "Alexandra", "initials": "A"}, {"family": "Hottenga", "given": "Jouke-Jan", "initials": "JJ"}, {"family": "Mbarek", "given": "Hamdi", "initials": "H"}, {"family": "Rivadeneira", "given": "Fernando", "initials": "F"}, {"family": "Tesli", "given": "Martin", "initials": "M"}, {"family": "van Beijsterveldt", "given": "Catharina", "initials": "C"}, {"family": "Breen", "given": "Gerome", "initials": "G"}, {"family": "Lewis", "given": "Cathryn M", "initials": "CM"}, {"family": "Thapar", "given": "Anita", "initials": "A"}, {"family": "Boomsma", "given": "Dorret I", "initials": "DI"}, {"family": "Kuja-Halkola", "given": "Ralf", "initials": "R"}, {"family": "Reichborn-Kjennerud", "given": "Ted", "initials": "T"}, {"family": "Magnus", "given": "Per", "initials": "P"}, {"family": "Rimfeld", "given": "Kaili", "initials": "K"}, {"family": "Ystrom", "given": "Eivind", "initials": "E"}, {"family": "Jarvelin", "given": "Marjo-Riitta", "initials": "MR"}, {"family": "Lichtenstein", "given": "Paul", "initials": "P"}, {"family": "Lundstrom", "given": "Sebastian", "initials": "S"}, {"family": "Munaf\u00f2", "given": "Marcus R", "initials": "MR"}, {"family": "Plomin", "given": "Robert", "initials": "R"}, {"family": "Tiemeier", "given": "Henning", "initials": "H"}, {"family": "Nivard", "given": "Michel G", "initials": "MG"}, {"family": "Bartels", "given": "Meike", "initials": "M"}, {"family": "Middeldorp", "given": "Christel M", "initials": "CM"}, {"family": "Bipolar Disorder and Major Depressive Disorder Working Groups of the Psychiatric Genomics Consortium", "given": "", "initials": ""}], "type": "journal article", "published": "2020-07-01", "journal": {"title": "JAMA Psychiatry", "issn": "2168-6238", "volume": "77", "issue": "7", "pages": "715-728", "issn-l": "2168-622X"}, "abstract": "Adult mood disorders are often preceded by behavioral and emotional problems in childhood. It is yet unclear what explains the associations between childhood psychopathology and adult traits.\n\nTo investigate whether genetic risk for adult mood disorders and associated traits is associated with childhood disorders.\n\nThis meta-analysis examined data from 7 ongoing longitudinal birth and childhood cohorts from the UK, the Netherlands, Sweden, Norway, and Finland. Starting points of data collection ranged from July 1985 to April 2002. Participants were repeatedly assessed for childhood psychopathology from ages 6 to 17 years. Data analysis occurred from September 2017 to May 2019.\n\nIndividual polygenic scores (PGS) were constructed in children based on genome-wide association studies of adult major depression, bipolar disorder, subjective well-being, neuroticism, insomnia, educational attainment, and body mass index (BMI).\n\nRegression meta-analyses were used to test associations between PGS and attention-deficit/hyperactivity disorder (ADHD) symptoms and internalizing and social problems measured repeatedly across childhood and adolescence and whether these associations depended on childhood phenotype, age, and rater.\n\nThe sample included 42 998 participants aged 6 to 17 years. Male participants varied from 43.0% (1040 of 2417 participants) to 53.1% (2434 of 4583 participants) by age and across all cohorts. The PGS of adult major depression, neuroticism, BMI, and insomnia were positively associated with childhood psychopathology (\u03b2 estimate range, 0.023-0.042 [95% CI, 0.017-0.049]), while associations with PGS of subjective well-being and educational attainment were negative (\u03b2, -0.026 to -0.046 [95% CI, -0.020 to -0.057]). There was no moderation of age, type of childhood phenotype, or rater with the associations. The exceptions were stronger associations between educational attainment PGS and ADHD compared with internalizing problems (\u0394\u03b2, 0.0561 [\u039495% CI, 0.0318-0.0804]; \u0394SE, 0.0124) and social problems (\u0394\u03b2, 0.0528 [\u039495% CI, 0.0282-0.0775]; \u0394SE, 0.0126), and between BMI PGS and ADHD and social problems (\u0394\u03b2, -0.0001 [\u039495% CI, -0.0102 to 0.0100]; \u0394SE, 0.0052), compared with internalizing problems (\u0394\u03b2, -0.0310 [\u039495% CI, -0.0456 to -0.0164]; \u0394SE, 0.0074). Furthermore, the association between educational attainment PGS and ADHD increased with age (\u0394\u03b2, -0.0032 [\u0394 95% CI, -0.0048 to -0.0017]; \u0394SE, 0.0008).\n\nResults from this study suggest the existence of a set of genetic factors influencing a range of traits across the life span with stable associations present throughout childhood. Knowledge of underlying mechanisms may affect treatment and long-term outcomes of individuals with psychopathology.", "doi": "10.1001/jamapsychiatry.2020.0527", "pmid": "32293669", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pii", "key": "2763801"}, {"db": "pmc", "key": "PMC7160753"}], "notes": [], "created": "2020-05-06T12:23:53.890Z", "modified": "2021-11-10T12:52:04.518Z"}, {"entity": "publication", "iuid": "0bb8912b1be1418985a2639354012484", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0bb8912b1be1418985a2639354012484.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0bb8912b1be1418985a2639354012484"}}, "title": "Association of Genetic Risk Factors for Psychiatric Disorders and Traits of These Disorders in a Swedish Population Twin Sample.", "authors": [{"family": "Taylor", "given": "Mark J", "initials": "MJ"}, {"family": "Martin", "given": "Joanna", "initials": "J"}, {"family": "Lu", "given": "Yi", "initials": "Y"}, {"family": "Brikell", "given": "Isabell", "initials": "I"}, {"family": "Lundstr\u00f6m", "given": "Sebastian", "initials": "S"}, {"family": "Larsson", "given": "Henrik", "initials": "H"}, {"family": "Lichtenstein", "given": "Paul", "initials": "P"}], "type": "journal article", "published": "2019-03-01", "journal": {"volume": "76", "issn": "2168-6238", "issue": "3", "pages": "280-289", "title": "JAMA Psychiatry", "issn-l": "2168-622X"}, "abstract": "Psychiatric traits associated with categorically defined psychiatric disorders are heritable and present to varying degrees in the general population. It is commonly assumed that diagnoses represent the extreme end of continuously distributed traits in the population, but this assumption has yet to be robustly tested for many psychiatric phenotypes.\n\nTo assess whether genetic risk factors associated with psychiatric disorders are also associated with continuous variation in milder population traits.\n\nThis study combined a novel twin analytic approach with polygenic risk score (PRS) analyses in a large population-based twin sample. Phenotypic and genetic data were available from the Child and Adolescent Twin Study in Sweden. Inpatient data were available for January 1, 1987, to December 31, 2014, and outpatient data for January 1, 2001, to December 31, 2013. The last day of follow-up was December 31, 2014. Data analysis was performed from January 1, 2017, to September 30, 2017.\n\nQuestionnaires that assessed traits of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), learning difficulties, tic disorders (TDs), obsessive-compulsive disorder (OCD), anxiety, major depressive disorder (MDD), mania, and psychotic experiences were administered to a large Swedish twin sample. Individuals with clinical psychiatric diagnoses were identified using the Swedish National Patient Register. Joint categorical/continuous twin modeling was used to estimate genetic correlations between psychiatric diagnoses and continuous traits. The PRSs for psychiatric disorders were calculated based on independent discovery genetic data. The association between PRSs for each disorder and associated continuous traits was tested.\n\nPhenotype data were available for 13 923 twin pairs (35.1% opposite sex and 31.7% same-sex females) at 9 years of age, 5165 pairs (36.9% opposite sex and 34.0% same-sex females) at 15 years of age, and 4273 pairs (36.5% opposite sex and 34.4% same-sex females) at 18 years of age. Genetic data were available for 13 412 individuals (50.2% females). Twin genetic correlations between numerous psychiatric diagnoses and corresponding traits ranged from 0.31 to 0.69. Disorder PRSs were associated with related population traits for ASD (\u03b2 [SE] = 0.04 [0.01] at 9 years of age), ADHD (\u03b2 [SE] = 0.27 [0.03] at 9 years of age), TDs (\u03b2 [SE] = 0.02 [0.004] at 9 years of age), OCD (\u03b2 [SE] = 0.13 [0.05] at 18 years of age), anxiety (\u03b2 [SE] = 0.18 [0.08] at 9 years of age; \u03b2 [SE] = 0.07 [0.02] at 15 years of age; and \u03b2 [SE] = 0.40 [0.17] at 18 years of age), MDD (\u03b2 [SE] = 0.10 [0.03] at 9 years of age; \u03b2 [SE] = 0.11 [0.02] at 15 years of age; and \u03b2 [SE] = 0.41 [0.10] at 18 years of age), and schizophrenia (\u03b2 [SE] = 0.02 [0.01] at 18 years of age). Polygenic risk scores for depressive symptoms were associated with MDD diagnoses (odds ratio, 1.16; 95% CI, 1.02-1.32).\n\nThese results suggest that genetic factors associated with psychiatric disorders are also associated with milder variation in characteristic traits throughout the general population for many psychiatric phenotypes. This study suggests that many psychiatric disorders are likely to be continuous phenotypes rather than the categorical entities currently defined in diagnostic manuals, which has strong implications for genetic research in particular.", "doi": "10.1001/jamapsychiatry.2018.3652", "pmid": "30566181", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pii", "key": "2718628"}, {"db": "pmc", "key": "PMC6439816"}], "notes": [], "created": "2019-01-04T09:53:06.069Z", "modified": "2021-06-21T13:52:28.878Z"}, {"entity": "publication", "iuid": "121b335763fe4c73a079f6d0059f9f97", "links": {"self": {"href": "https://publications.scilifelab.se/publication/121b335763fe4c73a079f6d0059f9f97.json"}, "display": {"href": "https://publications.scilifelab.se/publication/121b335763fe4c73a079f6d0059f9f97"}}, "title": "Evidence for Genetic Overlap Between Schizophrenia and Age at First Birth in Women.", "authors": [{"family": "Mehta", "given": "Divya", "initials": "D"}, {"family": "Tropf", "given": "Felix C", "initials": "FC"}, {"family": "Gratten", "given": "Jacob", "initials": "J"}, {"family": "Bakshi", "given": "Andrew", "initials": "A"}, {"family": "Zhu", "given": "Zhihong", "initials": "Z"}, {"family": "Bacanu", "given": "Silviu-Alin", "initials": "SA"}, {"family": "Hemani", "given": "Gibran", "initials": "G"}, {"family": "Magnusson", "given": "Patrik K E", "initials": "PK"}, {"family": "Barban", "given": "Nicola", "initials": "N"}, {"family": "Esko", "given": "T\u00f5nu", "initials": "T"}, {"family": "Metspalu", "given": "Andres", "initials": "A"}, {"family": "Snieder", "given": "Harold", "initials": "H"}, {"family": "Mowry", "given": "Bryan J", "initials": "BJ"}, {"family": "Kendler", "given": "Kenneth S", "initials": "KS"}, {"family": "Yang", "given": "Jian", "initials": "J"}, {"family": "Visscher", "given": "Peter M", "initials": "PM"}, {"family": "McGrath", "given": "John J", "initials": "JJ"}, {"family": "Mills", "given": "Melinda C", "initials": "MC"}, {"family": "Wray", "given": "Naomi R", "initials": "NR"}, {"family": "Lee", "given": "S Hong", "initials": "SH"}, {"family": "Schizophrenia Working Group of the Psychiatric Genomics Consortium, LifeLines Cohort Study, and TwinsUK", "given": null, "initials": null}, {"family": "Andreassen", "given": "Ole A", "initials": "OA"}, {"family": "Bramon", "given": "Elvira", "initials": "E"}, {"family": "Bruggeman", "given": "Richard", "initials": "R"}, {"family": "Buxbaum", "given": "Joseph D", "initials": "JD"}, {"family": "Cairns", "given": "Murray J", "initials": "MJ"}, {"family": "Cantor", "given": "Rita M", "initials": "RM"}, {"family": "Cloninger", "given": "C Robert", "initials": "CR"}, {"family": "Cohen", "given": "David", "initials": "D"}, {"family": "Crespo-Facorro", "given": "Benedicto", "initials": "B"}, {"family": "Darvasi", "given": "Ariel", "initials": "A"}, {"family": "DeLisi", "given": "Lynn E", "initials": "LE"}, {"family": "Dinan", "given": "Timothy", "initials": "T"}, {"family": "Djurovic", "given": "Srdjan", "initials": "S"}, {"family": "Donohoe", "given": "Gary", "initials": "G"}, {"family": "Drapeau", "given": "Elodie", "initials": "E"}, {"family": "Escott-Price", "given": "Valentina", "initials": "V"}, {"family": "Freimer", "given": "Nelson B", "initials": "NB"}, {"family": "Georgieva", "given": "Lyudmila", "initials": "L"}, {"family": "de Haan", "given": "Lieuwe", "initials": "L"}, {"family": "Henskens", "given": "Frans A", "initials": "FA"}, {"family": "Joa", "given": "Inge", "initials": "I"}, {"family": "Juli\u00e0", "given": "Antonio", "initials": "A"}, {"family": "Khrunin", "given": "Andrey", "initials": "A"}, {"family": "Lerer", "given": "Bernard", "initials": "B"}, {"family": "Limborska", "given": "Svetlana", "initials": "S"}, {"family": "Loughland", "given": "Carmel M", "initials": "CM"}, {"family": "Macek", "given": "Milan", "initials": "M"}, {"family": "Marsal", "given": "Sara", "initials": "S"}, {"family": "McCarley", "given": "Robert W", "initials": "RW"}, {"family": "McIntosh", "given": "Andrew M", "initials": "AM"}, {"family": "McQuillin", "given": "Andrew", "initials": "A"}, {"family": "Melegh", "given": "Bela", "initials": "B"}, {"family": "Michie", "given": "Patricia T", "initials": "PT"}, {"family": "Morris", "given": "Derek W", "initials": "DW"}, {"family": "Murphy", "given": "Kieran C", "initials": "KC"}, {"family": "Myin-Germeys", "given": "Inez", "initials": "I"}, {"family": "Olincy", "given": "Ann", "initials": "A"}, {"family": "Van Os", "given": "Jim", "initials": "J"}, {"family": "Pantelis", "given": "Christos", "initials": "C"}, {"family": "Posthuma", "given": "Danielle", "initials": "D"}, {"family": "Quested", "given": "Digby", "initials": "D"}, {"family": "Schall", "given": "Ulrich", "initials": "U"}, {"family": "Scott", "given": "Rodney J", "initials": "RJ"}, {"family": "Seidman", "given": "Larry J", "initials": "LJ"}, {"family": "Toncheva", "given": "Draga", "initials": "D"}, {"family": "Tooney", "given": "Paul A", "initials": "PA"}, {"family": "Waddington", "given": "John", "initials": "J"}, {"family": "Weinberger", "given": "Daniel R", "initials": "DR"}, {"family": "Weiser", "given": "Mark", "initials": "M"}, {"family": "Wu", "given": "Jing Qin", "initials": "JQ"}], "type": "journal article", "published": "2016-05-01", "journal": {"volume": "73", "issn": "2168-6238", "issue": "5", "pages": "497-505", "title": "JAMA Psychiatry", "issn-l": "2168-622X"}, "abstract": "A recently published study of national data by McGrath et al in 2014 showed increased risk of schizophrenia (SCZ) in offspring associated with both early and delayed parental age, consistent with a U-shaped relationship. However, it remains unclear if the risk to the child is due to psychosocial factors associated with parental age or if those at higher risk for SCZ tend to have children at an earlier or later age.\n\nTo determine if there is a genetic association between SCZ and age at first birth (AFB) using genetically informative but independently ascertained data sets.\n\nThis investigation used multiple independent genome-wide association study data sets. The SCZ sample comprised 18\u202f957 SCZ cases and 22\u202f673 controls in a genome-wide association study from the second phase of the Psychiatric Genomics Consortium, and the AFB sample comprised 12\u202f247 genotyped women measured for AFB from the following 4 community cohorts: Estonia (Estonian Genome Center Biobank, University of Tartu), the Netherlands (LifeLines Cohort Study), Sweden (Swedish Twin Registry), and the United Kingdom (TwinsUK). Schizophrenia genetic risk for each woman in the AFB community sample was estimated using genetic effects inferred from the SCZ genome-wide association study.\n\nWe tested if SCZ genetic risk was a significant predictor of response variables based on published polynomial functions that described the relationship between maternal age and SCZ risk in offspring in Denmark. We substituted AFB for maternal age in these functions, one of which was corrected for the age of the father, and found that the fit was superior for the model without adjustment for the father's age.\n\nWe observed a U-shaped relationship between SCZ risk and AFB in the community cohorts, consistent with the previously reported relationship between SCZ risk in offspring and maternal age when not adjusted for the age of the father. We confirmed that SCZ risk profile scores significantly predicted the response variables (coefficient of determination R2\u2009=\u20091.1E-03, P\u2009=\u20094.1E-04), reflecting the published relationship between maternal age and SCZ risk in offspring by McGrath et al in 2014.\n\nThis study provides evidence for a significant overlap between genetic factors associated with risk of SCZ and genetic factors associated with AFB. It has been reported that SCZ risk associated with increased maternal age is explained by the age of the father and that de novo mutations that occur more frequently in the germline of older men are the underlying causal mechanism. This explanation may need to be revised if, as suggested herein and if replicated in future studies, there is also increased genetic risk of SCZ in older mothers.", "doi": "10.1001/jamapsychiatry.2016.0129", "pmid": "27007234", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "2500042"}], "notes": [], "created": "2017-05-03T12:59:44.061Z", "modified": "2024-01-16T13:48:50.136Z"}, {"entity": "publication", "iuid": "e430c3c2465144f8b15ecfdbc0823217", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e430c3c2465144f8b15ecfdbc0823217.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e430c3c2465144f8b15ecfdbc0823217"}}, "title": "Meta-analysis of Genome-wide Association Studies for Neuroticism, and the Polygenic Association With Major Depressive Disorder.", "authors": [{"family": "Genetics of Personality Consortium", "given": null, "initials": null}, {"family": "de Moor", "given": "Marleen H M", "initials": "MH"}, {"family": "van den Berg", "given": "St\u00e9phanie M", "initials": "SM"}, {"family": "Verweij", "given": "Karin J H", "initials": "KJ"}, {"family": "Krueger", "given": "Robert F", "initials": "RF"}, {"family": "Luciano", "given": "Michelle", "initials": "M"}, {"family": "Arias Vasquez", "given": "Alejandro", "initials": "A"}, {"family": "Matteson", "given": "Lindsay K", "initials": "LK"}, {"family": "Derringer", "given": "Jaime", "initials": "J"}, {"family": "Esko", "given": "T\u00f5nu", "initials": "T"}, {"family": "Amin", "given": "Najaf", "initials": "N"}, {"family": "Gordon", "given": "Scott D", "initials": "SD"}, {"family": "Hansell", "given": "Narelle K", "initials": "NK"}, {"family": "Hart", "given": "Amy B", "initials": "AB"}, {"family": "Sepp\u00e4l\u00e4", "given": "Ilkka", "initials": "I"}, {"family": "Huffman", "given": "Jennifer E", "initials": "JE"}, {"family": "Konte", "given": "Bettina", "initials": "B"}, {"family": "Lahti", "given": "Jari", "initials": "J"}, {"family": "Lee", "given": "Minyoung", "initials": "M"}, {"family": "Miller", "given": "Mike", "initials": "M"}, {"family": "Nutile", "given": "Teresa", "initials": "T"}, {"family": "Tanaka", "given": "Toshiko", "initials": "T"}, {"family": "Teumer", "given": "Alexander", "initials": "A"}, {"family": "Viktorin", "given": "Alexander", "initials": "A"}, {"family": "Wedenoja", "given": "Juho", "initials": "J"}, {"family": "Abecasis", "given": "Goncalo R", "initials": "GR"}, {"family": "Adkins", "given": "Daniel E", "initials": "DE"}, {"family": "Agrawal", "given": "Arpana", "initials": "A"}, {"family": "Allik", "given": "J\u00fcri", "initials": "J"}, {"family": "Appel", "given": "Katja", "initials": "K"}, {"family": "Bigdeli", "given": "Timothy B", "initials": "TB"}, {"family": "Busonero", "given": "Fabio", "initials": "F"}, {"family": "Campbell", "given": "Harry", "initials": "H"}, {"family": "Costa", "given": "Paul T", "initials": "PT"}, {"family": "Davey Smith", "given": "George", "initials": "G"}, {"family": "Davies", "given": "Gail", "initials": "G"}, {"family": "de Wit", "given": "Harriet", "initials": "H"}, {"family": "Ding", "given": "Jun", "initials": "J"}, {"family": "Engelhardt", "given": "Barbara E", "initials": "BE"}, {"family": "Eriksson", "given": "Johan G", "initials": "JG"}, {"family": "Fedko", "given": "Iryna O", "initials": "IO"}, {"family": "Ferrucci", "given": "Luigi", "initials": "L"}, {"family": "Franke", "given": "Barbara", "initials": "B"}, {"family": "Giegling", "given": "Ina", "initials": "I"}, {"family": "Grucza", "given": "Richard", "initials": "R"}, {"family": "Hartmann", "given": "Annette M", "initials": "AM"}, {"family": "Heath", "given": "Andrew C", "initials": "AC"}, {"family": "Heinonen", "given": "Kati", "initials": "K"}, {"family": "Henders", "given": "Anjali K", "initials": "AK"}, {"family": "Homuth", "given": "Georg", "initials": "G"}, {"family": "Hottenga", "given": "Jouke-Jan", "initials": "JJ"}, {"family": "Iacono", "given": "William G", "initials": "WG"}, {"family": "Janzing", "given": "Joost", "initials": "J"}, {"family": "Jokela", "given": "Markus", "initials": "M"}, {"family": "Karlsson", "given": "Robert", "initials": "R"}, {"family": "Kemp", "given": "John P", "initials": "JP"}, {"family": "Kirkpatrick", "given": "Matthew G", "initials": "MG"}, {"family": "Latvala", "given": "Antti", "initials": "A"}, {"family": "Lehtim\u00e4ki", "given": "Terho", "initials": "T"}, {"family": "Liewald", "given": "David C", "initials": "DC"}, {"family": "Madden", "given": "Pamela A F", "initials": "PA"}, {"family": "Magri", "given": "Chiara", "initials": "C"}, {"family": "Magnusson", "given": "Patrik K E", "initials": "PK"}, {"family": "Marten", "given": "Jonathan", "initials": "J"}, {"family": "Maschio", "given": "Andrea", "initials": "A"}, {"family": "Medland", "given": "Sarah 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"Sorice", "given": "Rossella", "initials": "R"}, {"family": "Starr", "given": "John M", "initials": "JM"}, {"family": "St Pourcain", "given": "Beate", "initials": "B"}, {"family": "Sutin", "given": "Angelina R", "initials": "AR"}, {"family": "Timpson", "given": "Nicholas J", "initials": "NJ"}, {"family": "Trochet", "given": "Holly", "initials": "H"}, {"family": "Vermeulen", "given": "Sita", "initials": "S"}, {"family": "Vuoksimaa", "given": "Eero", "initials": "E"}, {"family": "Widen", "given": "Elisabeth", "initials": "E"}, {"family": "Wouda", "given": "Jasper", "initials": "J"}, {"family": "Wright", "given": "Margaret J", "initials": "MJ"}, {"family": "Zgaga", "given": "Lina", "initials": "L"}, {"family": "Porteous", "given": "David", "initials": "D"}, {"family": "Minelli", "given": "Alessandra", "initials": "A"}, {"family": "Palmer", "given": "Abraham A", "initials": "AA"}, {"family": "Rujescu", "given": "Dan", "initials": "D"}, {"family": "Ciullo", "given": "Marina", "initials": "M"}, {"family": "Hayward", "given": "Caroline", "initials": "C"}, {"family": "Rudan", "given": "Igor", "initials": "I"}, {"family": "Metspalu", "given": "Andres", "initials": "A"}, {"family": "Kaprio", "given": "Jaakko", "initials": "J"}, {"family": "Deary", "given": "Ian J", "initials": "IJ"}, {"family": "R\u00e4ikk\u00f6nen", "given": "Katri", "initials": "K"}, {"family": "Wilson", "given": "James F", "initials": "JF"}, {"family": "Keltikangas-J\u00e4rvinen", "given": "Liisa", "initials": "L"}, {"family": "Bierut", "given": "Laura J", "initials": "LJ"}, {"family": "Hettema", "given": "John M", "initials": "JM"}, {"family": "Grabe", "given": "Hans J", "initials": "HJ"}, {"family": "van Duijn", "given": "Cornelia M", "initials": "CM"}, {"family": "Evans", "given": "David M", "initials": "DM"}, {"family": "Schlessinger", "given": "David", "initials": "D"}, {"family": "Pedersen", "given": "Nancy L", "initials": "NL"}, {"family": "Terracciano", "given": "Antonio", "initials": "A"}, {"family": "McGue", "given": "Matt", "initials": "M"}, {"family": "Penninx", "given": "Brenda W J H", "initials": "BW"}, {"family": "Martin", "given": "Nicholas G", "initials": "NG"}, {"family": "Boomsma", "given": "Dorret I", "initials": "DI"}], "type": "journal article", "published": "2015-07-00", "journal": {"volume": "72", "issn": "2168-6238", "issue": "7", "pages": "642-650", "title": "JAMA Psychiatry", "issn-l": "2168-622X"}, "abstract": "Neuroticism is a pervasive risk factor for psychiatric conditions. It genetically overlaps with major depressive disorder (MDD) and is therefore an important phenotype for psychiatric genetics. The Genetics of Personality Consortium has created a resource for genome-wide association analyses of personality traits in more than 63,000 participants (including MDD cases).\n\nTo identify genetic variants associated with neuroticism by performing a meta-analysis of genome-wide association results based on 1000 Genomes imputation; to evaluate whether common genetic variants as assessed by single-nucleotide polymorphisms (SNPs) explain variation in neuroticism by estimating SNP-based heritability; and to examine whether SNPs that predict neuroticism also predict MDD.\n\nGenome-wide association meta-analysis of 30 cohorts with genome-wide genotype, personality, and MDD data from the Genetics of Personality Consortium. The study included 63,661 participants from 29 discovery cohorts and 9786 participants from a replication cohort. Participants came from Europe, the United States, or Australia. Analyses were conducted between 2012 and 2014.\n\nNeuroticism scores harmonized across all 29 discovery cohorts by item response theory analysis, and clinical MDD case-control status in 2 of the cohorts.\n\nA genome-wide significant SNP was found on 3p14 in MAGI1 (rs35855737; P\u2009=\u20099.26\u2009\u00d7\u200910-9 in the discovery meta-analysis). This association was not replicated (P\u2009=\u2009.32), but the SNP was still genome-wide significant in the meta-analysis of all 30 cohorts (P\u2009=\u20092.38\u2009\u00d7\u200910-8). Common genetic variants explain 15% of the variance in neuroticism. Polygenic scores based on the meta-analysis of neuroticism in 27 cohorts significantly predicted neuroticism (1.09\u2009\u00d7\u200910-12\u2009<\u2009P\u2009<\u2009.05) and MDD (4.02\u2009\u00d7\u200910-9\u2009<\u2009P\u2009<\u2009.05) in the 2 other cohorts.\n\nThis study identifies a novel locus for neuroticism. The variant is located in a known gene that has been associated with bipolar disorder and schizophrenia in previous studies. In addition, the study shows that neuroticism is influenced by many genetic variants of small effect that are either common or tagged by common variants. These genetic variants also influence MDD. Future studies should confirm the role of the MAGI1 locus for neuroticism and further investigate the association of MAGI1 and the polygenic association to a range of other psychiatric disorders that are phenotypically correlated with neuroticism.", "doi": "10.1001/jamapsychiatry.2015.0554", "pmid": "25993607", "labels": {"National Genomics Infrastructure": null, "NGI Uppsala (SNP&SEQ Technology Platform)": null}, "xrefs": [{"db": "pii", "key": "2294268"}, {"db": "pmc", "key": "PMC4667957"}, {"db": "mid", "key": "NIHMS738804"}], "notes": [], "created": "2017-05-02T12:57:04.891Z", "modified": "2020-01-21T13:56:05.852Z"}], "created": "2017-05-09T09:12:27.525Z", "modified": "2020-11-27T13:14:09.418Z"}