Olav Bjerkehagen Smeland

• Koch, Elise Mirjam; Kämpe, Anders; Alver, Maris; Sigurðarson, Sindri; Einarsson, Guðmundur & Partanen, Juulia [Vis alle 21 forfattere av denne artikkelen] (2024). Polygenic liability for antipsychotic dosage and polypharmacy - a real-world registry and biobank study. Neuropsychopharmacology. ISSN 0893-133X. doi: 10.1038/s41386-023-01792-0.
• Docherty, Anna R.; Mullins, Niamh; Ashley-Koch, Allison E.; Qin, Xuejun; Coleman, Jonathan R.I. & Shabalin, Andrey [Vis alle 51 forfattere av denne artikkelen] (2023). GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors. American Journal of Psychiatry. ISSN 0002-953X. 180(10), s. 723–738. doi: 10.1176/appi.ajp.21121266.
• Holen, Børge; Kutrolli, Gleda; Shadrin, Alexey; Icick, Romain; Hindley, Guy & Rødevand, Linn [Vis alle 16 forfattere av denne artikkelen] (2023). Genome-wide analyses reveal shared genetic architecture and novel risk loci between opioid use disorder and general cognitive ability. Drug and Alcohol Dependence. ISSN 0376-8716. 256. doi: 10.1016/j.drugalcdep.2023.111058. Fulltekst i vitenarkiv
• van der Meer, Dennis; Cheng, Weiqiu; Rokicki, Jaroslav; Fernandez-Cabello, Sara; Shadrin, Alexey & Smeland, Olav Bjerkehagen [Vis alle 19 forfattere av denne artikkelen] (2023). Clustering Schizophrenia Genes by Their Temporal Expression Patterns Aids Functional Interpretation. Schizophrenia Bulletin. ISSN 0586-7614. 50(2), s. 327–338. doi: 10.1093/schbul/sbad140. Fulltekst i vitenarkiv
• Jaholkowski, Piotr Pawel; Hindley, Guy; Shadrin, Alexey; Tesfaye, Markos ; Bahrami, Shahram & Nerhus, Mari [Vis alle 19 forfattere av denne artikkelen] (2023). Genome-wide Association Analysis of Schizophrenia and Vitamin D Levels Shows Shared Genetic Architecture and Identifies Novel Risk Loci. Schizophrenia Bulletin. ISSN 0586-7614. 49(6), s. 1654–1664. doi: 10.1093/schbul/sbad063. Fulltekst i vitenarkiv
• Rødevand, Linn Nilsen; Rahman, Zillur; Hindley, Guy Frederick Lanyon; Smeland, Olav Bjerkehagen; Frei, Oleksandr & Filiz, Tahir Tekin [Vis alle 15 forfattere av denne artikkelen] (2023). Characterizing the Shared Genetic Underpinnings of Schizophrenia and Cardiovascular Disease Risk Factors. American Journal of Psychiatry. ISSN 0002-953X. 180(11), s. 815–826. doi: 10.1176/APPI.AJP.20220660.
• Requena Osete, Jordi; Akkouh, Ibrahim Ahmed; Ievglevskyi, Oleksandr; Vandenberghe, Matthieu; Reis de Assis, Denis & Ueland, Thor [Vis alle 14 forfattere av denne artikkelen] (2023). Characterization of lithium (Li) treated human cortical spheroids (hCS). Molecular Psychiatry. ISSN 1359-4184. 28(7). doi: 10.1038/s41380-023-02300-y.
• Akkouh, Ibrahim Ahmed; Ueland, Thor; Szabo, Attila; Hughes, Timothy; Smeland, Olav Bjerkehagen & Andreassen, Ole [Vis alle 8 forfattere av denne artikkelen] (2023). Longitudinal Transcriptomic Analysis of Human Cortical Spheroids Identifies Axonal Dysregulation in the Prenatal Brain as a Mediator of Genetic Risk for Schizophrenia. Biological Psychiatry. ISSN 0006-3223. 0, s. 1–12. doi: 10.1016/j.biopsych.2023.08.017. Fulltekst i vitenarkiv
• Steen, Nils Eiel; Rahman, Zillur; Szabo, Attila; Hindley, Guy; Parker, Nadine & Cheng, Weiqiu [Vis alle 20 forfattere av denne artikkelen] (2023). Shared Genetic Loci Between Schizophrenia and White Blood Cell Counts Suggest Genetically Determined Systemic Immune Abnormalities. Schizophrenia Bulletin. ISSN 0586-7614. 49(5), s. 1345–1354. doi: 10.1093/schbul/sbad082. Fulltekst i vitenarkiv
• Parker, Nadine; Cheng, Weiqiu; Hindley, Guy; Parekh, Pravesh; Shadrin, Alexey & Maximov, Ivan [Vis alle 12 forfattere av denne artikkelen] (2023). Psychiatric disorders and brain white matter exhibit genetic overlap implicating developmental and neural cell biology. Molecular Psychiatry. ISSN 1359-4184. doi: 10.1038/s41380-023-02264-z.
• Hindley, Guy; Drange, Ole Kristian; Lin, Aihua; Kutrolli, Gleda; Shadrin, Alexey & Parker, Nadine [Vis alle 20 forfattere av denne artikkelen] (2023). Cross-trait genome-wide association analysis of C-reactive protein level and psychiatric disorders. Psychoneuroendocrinology. ISSN 0306-4530. 157. doi: 10.1016/j.psyneuen.2023.106368. Fulltekst i vitenarkiv
• Woldeyohannes, Markos Tesfaye; Jaholkowski, Piotr Pawel; Hindley, Guy; Shadrin, Alexey; Rahman, Zillur & Bahrami, Shahram [Vis alle 17 forfattere av denne artikkelen] (2023). Shared genetic architecture between irritable bowel syndrome and psychiatric disorders reveals molecular pathways of the gut-brain axis. Genome Medicine. ISSN 1756-994X. 15(1). doi: 10.1186/s13073-023-01212-4. Fulltekst i vitenarkiv
• Wang, Hao; Makowski, Carolina; Zhang, Yanxiao; Qi, Anna; Kaufmann, Tobias Herbert & Smeland, Olav Bjerkehagen [Vis alle 10 forfattere av denne artikkelen] (2023). Chromosomal inversion polymorphisms shape human brain morphology. Cell reports. ISSN 2211-1247. 42(8). doi: 10.1016/j.celrep.2023.112896. Fulltekst i vitenarkiv
• Bang, Lasse; Bahrami, Shahram; Hindley, Guy; Smeland, Olav Bjerkehagen; Rødevand, Linn & Jaholkowski, Piotr Pawel [Vis alle 18 forfattere av denne artikkelen] (2023). Genome-wide analysis of anorexia nervosa and major psychiatric disorders and related traits reveals genetic overlap and identifies novel risk loci for anorexia nervosa. Translational Psychiatry. ISSN 2158-3188. 13. doi: 10.1038/s41398-023-02585-1. Fulltekst i vitenarkiv
• Karadag, Naz; Shadrin, Alexey; O'Connell, Kevin Sean; Hindley, Guy Frederick Lanyon; Rahman, Zillur & Parker, Nadine [Vis alle 18 forfattere av denne artikkelen] (2023). Identification of novel genomic risk loci shared between common epilepsies and psychiatric disorders. Brain. ISSN 0006-8950. 146(8), s. 3392–3403. doi: 10.1093/brain/awad038. Fulltekst i vitenarkiv
• Parker, Nadine; Cheng, Weiqiu; Hindley, Guy; O'Connell, Kevin Sean; Karthikeyan, Sandeep & Holen, Børge [Vis alle 19 forfattere av denne artikkelen] (2023). Genetic Overlap Between Global Cortical Brain Structure, C-Reactive Protein, and White Blood Cell Counts. Biological Psychiatry. ISSN 0006-3223. doi: 10.1016/j.biopsych.2023.06.008. Fulltekst i vitenarkiv
• Hindley, Guy Frederick Lanyon; Shadrin, Alexey; van der Meer, Dennis; Parker, Nadine; Cheng, Weiqiu & O'Connell, Kevin Sean [Vis alle 23 forfattere av denne artikkelen] (2023). Multivariate genetic analysis of personality and cognitive traits reveals abundant pleiotropy. Nature Human Behaviour. ISSN 2397-3374. 7, s. 1584–1600. doi: 10.1038/s41562-023-01630-9.
• Reas, Emilie T.; Shadrin, Alexey; Frei, Oleksandr; Motazedi, Ehsan; McEvoy, Linda & Bahrami, Shahram [Vis alle 22 forfattere av denne artikkelen] (2023). Improved multimodal prediction of progression from MCI to Alzheimer's disease combining genetics with quantitative brain MRI and cognitive measures. Alzheimer's & Dementia. ISSN 1552-5260. 19(11), s. 5151–5158. doi: 10.1002/alz.13112. Fulltekst i vitenarkiv
• O'Connell, Kevin Sean; Koch, Elise; Lenk, Hasan Cagin; Akkouh, Ibrahim Ahmed; Hindley, Guy Frederick Lanyon & Jaholkowski, Piotr Pawel [Vis alle 16 forfattere av denne artikkelen] (2023). Polygenic overlap with body-mass index improves prediction of treatment-resistant schizophrenia. Psychiatry Research. ISSN 0165-1781. 325. doi: 10.1016/j.psychres.2023.115217. Fulltekst i vitenarkiv
• Holen, Børge; Shadrin, Alexey; Icick, Romain; Filiz, Tahir Tekin; Hindley, Guy Frederick Lanyon & Rødevand, Linn [Vis alle 19 forfattere av denne artikkelen] (2023). Genome-wide analyses reveal novel opioid use disorder loci and genetic overlap with schizophrenia, bipolar disorder, and major depression. Addiction Biology. ISSN 1355-6215. 28(6). doi: 10.1111/adb.13282. Fulltekst i vitenarkiv
• Cheng, Weiqiu; Parker, Nadine; Karadag, Naz; Koch, Elise; Hindley, Guy Frederick Lanyon & Icick, Romain [Vis alle 22 forfattere av denne artikkelen] (2023). The relationship between cannabis use, schizophrenia, and bipolar disorder: a genetically informed study. The Lancet Psychiatry. ISSN 2215-0374. 10(6), s. 441–451. doi: 10.1016/S2215-0366(23)00143-8. Fulltekst i vitenarkiv
• Birkenæs, Viktoria; Bakken, Nora Refsum; Frei, Evgeniia; Jaholkowski, Piotr Pawel; Smeland, Olav Bjerkehagen & Woldeyohannes, Markos Tesfaye [Vis alle 15 forfattere av denne artikkelen] (2023). Psychometric Properties and Diagnostic Associations of the Short-Form Community Assessment of Psychic Experiences in a Population-Based Sample of 29 021 Adult Men. Schizophrenia Bulletin. ISSN 0586-7614. 49(5), s. 1229–1238. doi: 10.1093/schbul/sbad074. Fulltekst i vitenarkiv
• Jaholkowski, Piotr; Shadrin, Alexey A.; Jangmo, Andreas; Frei, Evgeniia; Woldeyohannes, Markos Tesfaye & Hindley, Guy F. L. [Vis alle 23 forfattere av denne artikkelen] (2023). Associations Between Symptoms of Premenstrual Disorders and Polygenic Liability for Major Psychiatric Disorders. JAMA psychiatry. ISSN 2168-6238. 80(7), s. 738–742. doi: 10.1001/jamapsychiatry.2023.1137.
• Osete, Jordi Requena; Akkouh, Ibrahim Ahmed; Ievglevskyi, Oleksandr; Vandenberghe, Matthieu; Reis de Assis, Denis & Ueland, Thor [Vis alle 14 forfattere av denne artikkelen] (2023). Transcriptional and functional effects of lithium in bipolar disorder iPSC-derived cortical spheroids. Molecular Psychiatry. ISSN 1359-4184. 28, s. 3033–3043. doi: 10.1038/s41380-023-01944-0. Fulltekst i vitenarkiv
• Andreassen, Ole; Hindley, Guy Frederick Lanyon; Frei, Oleksandr & Smeland, Olav Bjerkehagen (2023). New insights from the last decade of research in psychiatric genetics: discoveries, challenges and clinical implications. World Psychiatry. ISSN 1723-8617. 22(1), s. 4–24. doi: 10.1002/wps.21034.
• Bahrami, Shahram; Hindley, Guy Frederick Lanyon; Winsvold, Bendik Slagvold; O`Connell, Kevin S.; Frei, Oleksandr & Shadrin, Alexey [Vis alle 16 forfattere av denne artikkelen] (2022). Dissecting the shared genetic basis of migraine and mental disorders using novel statistical tools. Brain. ISSN 0006-8950. doi: 10.1093/brain/awab267.
• Hindley, Guy Frederick Lanyon; O'Connell, Kevin Sean; Rahman, Zillur; Frei, Oleksandr; Bahrami, Shahram & Shadrin, Alexey [Vis alle 17 forfattere av denne artikkelen] (2022). The shared genetic basis of mood instability and psychiatric disorders: A cross-trait genome-wide association analysis. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics. ISSN 1552-4841. 189(6), s. 207–218. doi: 10.1002/ajmg.b.32907. Fulltekst i vitenarkiv
• Cheng, Weiqiu; van der Meer, Dennis; Parker, Nadine; Hindley, Guy Frederick Lanyon; O'Connell, Kevin Sean & Wang, Yunpeng [Vis alle 20 forfattere av denne artikkelen] (2022). Shared genetic architecture between schizophrenia and subcortical brain volumes implicates early neurodevelopmental processes and brain development in childhood. Molecular Psychiatry. ISSN 1359-4184. doi: 10.1038/s41380-022-01751-z. Fulltekst i vitenarkiv
• Torgersen, Kristin Stensland; Rahman, Zillur; Bahrami, Shahram; Hindley, Guy Frederick Lanyon; Parker, Nadine & Frei, Oleksandr [Vis alle 14 forfattere av denne artikkelen] (2022). Shared genetic loci between depression and cardiometabolic traits. PLoS Genetics. ISSN 1553-7390. 18(5). doi: 10.1371/journal.pgen.1010161. Fulltekst i vitenarkiv
• Hindley, Guy; Frei, Oleksandr; Shadrin, Alexey; Cheng, Weiqiu; O'Connell, Kevin Sean & Icick, Romain [Vis alle 17 forfattere av denne artikkelen] (2022). Charting the Landscape of Genetic Overlap Between Mental Disorders and Related Traits Beyond Genetic Correlation. American Journal of Psychiatry. ISSN 0002-953X. 179(11), s. 833–843. doi: 10.1176/appi.ajp.21101051.
• Icick, Romain; Shadrin, Alexey; Holen, Børge; Karadag, Naz; Lin, Aihua & Hindley, Guy [Vis alle 17 forfattere av denne artikkelen] (2022). Genetic overlap between mood instability and alcohol-related phenotypes suggests shared biological underpinnings. Neuropsychopharmacology. ISSN 0893-133X. 47, s. 1883–1891. doi: 10.1038/s41386-022-01401-6.
• Smeland, Olav Bjerkehagen & Andreassen, Ole (2022). Schizophrenia: genetic insights with clinical potential. Nature Reviews Neurology. ISSN 1759-4758. 18, s. 129–130. doi: 10.1038/s41582-021-00613-6.
• Streit, Fabian; Witt, Stephanie H.; Awasthi, Swapnil; Foo, Jerome C.; Jungkunz, Martin & Frank, Josef [Vis alle 30 forfattere av denne artikkelen] (2022). Borderline personality disorder and the big five: molecular genetic analyses indicate shared genetic architecture with neuroticism and openness. Translational Psychiatry. ISSN 2158-3188. 12:153, s. 1–8. doi: 10.1038/s41398-022-01912-2. Fulltekst i vitenarkiv
• van der Meer, Dennis; Shadrin, Alexey; O'Connell, Kevin Sean; Bettella, Francesco; Djurovic, Srdjan & Wolfers, Thomas [Vis alle 17 forfattere av denne artikkelen] (2022). Boosting Schizophrenia Genetics by Utilizing Genetic Overlap With Brain Morphology. Biological Psychiatry. ISSN 0006-3223. 92(4), s. 291–298. doi: 10.1016/j.biopsych.2021.12.007. Fulltekst i vitenarkiv
• Bahrami, Shahram; Hindley, Guy Frederick Lanyon; Winsvold, Bendik K S; O'Connell, Kevin Sean; Frei, Oleksandr & Shadrin, Alexey [Vis alle 39 forfattere av denne artikkelen] (2022). Dissecting the shared genetic basis of migraine and mental disorders using novel statistical tools. Brain. ISSN 0006-8950. 145(1), s. 142–153. doi: 10.1093/brain/awab267. Fulltekst i vitenarkiv Vis sammendrag

  Migraine is three times more prevalent in people with bipolar disorder or depression. The relationship between schizophrenia and migraine is less certain although glutamatergic and serotonergic neurotransmission are implicated in both. A shared genetic basis to migraine and mental disorders has been suggested but previous studies have reported weak or non-significant genetic correlations and five shared risk loci. Using the largest samples to date and novel statistical tools, we aimed to determine the extent to which migraine’s polygenic architecture overlaps with bipolar disorder, depression and schizophrenia beyond genetic correlation, and to identify shared genetic loci. Summary statistics from genome-wide association studies were acquired from large-scale consortia for migraine (n cases = 59 674; n controls = 316 078), bipolar disorder (n cases = 20 352; n controls = 31 358), depression (n cases = 170 756; n controls = 328 443) and schizophrenia (n cases = 40 675, n controls = 64 643). We applied the bivariate causal mixture model to estimate the number of disorder-influencing variants shared between migraine and each mental disorder, and the conditional/conjunctional false discovery rate method to identify shared loci. Loci were functionally characterized to provide biological insights. Univariate MiXeR analysis revealed that migraine was substantially less polygenic (2.8 K disorder-influencing variants) compared to mental disorders (8100–12 300 disorder-influencing variants). Bivariate analysis estimated that 800 (SD = 300), 2100 (SD = 100) and 2300 (SD = 300) variants were shared between bipolar disorder, depression and schizophrenia, respectively. There was also extensive overlap with intelligence (1800, SD = 300) and educational attainment (2100, SD = 300) but not height (1000, SD = 100). We next identified 14 loci jointly associated with migraine and depression and 36 loci jointly associated with migraine and schizophrenia, with evidence of consistent genetic effects in independent samples. No loci were associated with migraine and bipolar disorder. Functional annotation mapped 37 and 298 genes to migraine and each of depression and schizophrenia, respectively, including several novel putative migraine genes such as L3MBTL2, CACNB2 and SLC9B1. Gene-set analysis identified several putative gene sets enriched with mapped genes including transmembrane transport in migraine and schizophrenia. Most migraine-influencing variants were predicted to influence depression and schizophrenia, although a minority of mental disorder-influencing variants were shared with migraine due to the difference in polygenicity. Similar overlap with other brain-related phenotypes suggests this represents a pool of ‘pleiotropic’ variants that influence vulnerability to diverse brain-related disorders and traits. We also identified specific loci shared between migraine and each of depression and schizophrenia, implicating shared molecular mechanisms and highlighting candidate migraine genes for experimental validation.

• Mullins, Niamh; Kang, JooEun; Campos, Adrian I.; Coleman, Jonathan R.I.; Edwards, Alexis C. & Galfalvy, Hanga [Vis alle 52 forfattere av denne artikkelen] (2022). Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors. Biological Psychiatry. ISSN 0006-3223. 91(3), s. 313–327. doi: 10.1016/j.biopsych.2021.05.029. Fulltekst i vitenarkiv Vis sammendrag

  Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.

• Hindley, Guy Frederick Lanyon; Bahrami, Shahram; Steen, Nils Eiel; O’Connell, Kevin S.; Frei, Oleksandr & Shadrin, Alexey [Vis alle 13 forfattere av denne artikkelen] (2021). Characterising the shared genetic determinants of bipolar disorder, schizophrenia and risk-taking. Translational Psychiatry. ISSN 2158-3188. doi: 10.1038/s41398-021-01576-4.
• Blokland, Gabriella A. M.; Grove, Jakob; Chen, Chia-Yen; Cotsapas, Chris; Tobet, Stuart & Handa, Robert [Vis alle 50 forfattere av denne artikkelen] (2021). Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders. Biological Psychiatry. ISSN 0006-3223. 91, s. 102–117. doi: 10.1016/j.biopsych.2021.02.972. Fulltekst i vitenarkiv Vis sammendrag

  Background Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. Methods We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. Results Across disorders, genome-wide significant single nucleotide polymorphism–by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10−8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10−6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10−7; rs73033497, p = 8.8 × 10−7; rs7914279, p = 6.4 × 10−7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10−7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10−7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10−7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). Conclusions In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels.

• Krull, Florian; Akkouh, Ibrahim Ahmed; Hughes, Timothy; Bettella, Francesco; Athanasiu, Lavinia & Smeland, Olav Bjerkehagen [Vis alle 12 forfattere av denne artikkelen] (2021). Dose-dependent transcriptional effects of lithium and adverse effect burden in a psychiatric cohort. Progress in Neuro-psychopharmacology and Biological Psychiatry. ISSN 0278-5846. 112. doi: 10.1016/j.pnpbp.2021.110408. Fulltekst i vitenarkiv
• Kalman, Janos L.; Loohuis, Loes M. Olde; Vreeker, Annabel; McQuillin, Andrew; Stahl, Eli A. & Ruderfer, Douglas [Vis alle 50 forfattere av denne artikkelen] (2021). Characterisation of age and polarity at onset in bipolar disorder. British Journal of Psychiatry. ISSN 0007-1250. 219(6), s. 659–669. doi: 10.1192/bjp.2021.102. Fulltekst i vitenarkiv
• Mullins, Niamh; Forstner, Andreas J.; O'Connell, Kevin Sean; Coombes, Brandon; Coleman, Jonathan R. I. & Qiao, Zhen [Vis alle 59 forfattere av denne artikkelen] (2021). Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology. Nature Genetics. ISSN 1061-4036. 53, s. 817–829. doi: 10.1038/s41588-021-00857-4.
• Andlauer, Till F.M.; Guzman-Parra, José; Streit, Fabian; Strohmaier, Jana; González, Maria José & Flores, Susana Gil [Vis alle 50 forfattere av denne artikkelen] (2021). Bipolar multiplex families have an increased burden of common risk variants for psychiatric disorders. Molecular Psychiatry. ISSN 1359-4184. 26, s. 1286–1298. doi: 10.1038/s41380-019-0558-2. Fulltekst i vitenarkiv
• Shadrin, Alexey A.; Kaufmann, Tobias; van der Meer, Dennis; Palmer, Clare E.; Makowski, Carolina & Loughnan, Robert [Vis alle 22 forfattere av denne artikkelen] (2021). Vertex-wise multivariate genome-wide association study identifies 780 unique genetic loci associated with cortical morphology. NeuroImage. ISSN 1053-8119. 244, s. 1–8. doi: 10.1016/j.neuroimage.2021.118603. Fulltekst i vitenarkiv
• Szabo, Attila; Akkouh, Ibrahim A.; Vandenberghe, Matthieu; Osete, Jordi Requena; Hughes, Timothy & Heine, Vivi [Vis alle 10 forfattere av denne artikkelen] (2021). A human iPSC-astroglia neurodevelopmental model reveals divergent transcriptomic patterns in schizophrenia. Translational Psychiatry. ISSN 2158-3188. 11(1). doi: 10.1038/s41398-021-01681-4. Fulltekst i vitenarkiv
• Wiström, Erik David; O'Connell, Kevin Sean; Karadag, Naz; Bahrami, Shahram; Hindley, Guy Frederick Lanyon & Lin, Aihua [Vis alle 14 forfattere av denne artikkelen] (2021). Genome-wide analysis reveals genetic overlap between alcohol use behaviours, schizophrenia and bipolar disorder and identifies novel shared risk loci. Addiction. ISSN 0965-2140. doi: 10.1111/add.15680. Fulltekst i vitenarkiv
• Monereo-Sánchez, Jennifer; Schram, Miranda T.; Frei, Oleksandr; O'Connell, Kevin Sean; Shadrin, Alexey & Smeland, Olav Bjerkehagen [Vis alle 11 forfattere av denne artikkelen] (2021). Genetic Overlap Between Alzheimer’s Disease and Depression Mapped Onto the Brain. Frontiers in Neuroscience. ISSN 1662-4548. 15, s. 1–9. doi: 10.3389/fnins.2021.653130. Fulltekst i vitenarkiv
• O'Connell, Kevin Sean; Frei, Oleksandr; Bahrami, Shahram; Smeland, Olav Bjerkehagen; Bettella, Francesco & Cheng, Weiqiu [Vis alle 16 forfattere av denne artikkelen] (2021). Characterizing the Genetic Overlap Between Psychiatric Disorders and Sleep-Related Phenotypes. Biological Psychiatry. ISSN 0006-3223. s. 1–11. doi: 10.1016/j.biopsych.2021.07.007. Fulltekst i vitenarkiv
• Hindley, Guy Frederick Lanyon; Bahrami, Shahram; Steen, Nils Eiel; O'Connell, Kevin Sean; Frei, Oleksandr & Shadrin, Alexey [Vis alle 13 forfattere av denne artikkelen] (2021). Characterising the shared genetic determinants of bipolar disorder, schizophrenia and risk-taking. Translational Psychiatry. ISSN 2158-3188. 11:466, s. 1–10. doi: 10.1038/s41398-021-01576-4. Fulltekst i vitenarkiv
• Elvsåshagen, Torbjørn; Shadrin, Alexey; Frei, Oleksandr; van der Meer, Dennis; Bahrami, Shahram & Kumar, Vinod J. [Vis alle 10 forfattere av denne artikkelen] (2021). The genetic architecture of the human thalamus and its overlap with ten common brain disorders. Nature Communications. ISSN 2041-1723. 12(1). doi: 10.1038/s41467-021-23175-z. Fulltekst i vitenarkiv
• Holland, Dominic; Frei, Oleksandr; Desikan, Rahul S.; Fan, Chun Chieh; Shadrin, Alexey & Smeland, Olav Bjerkehagen [Vis alle 8 forfattere av denne artikkelen] (2021). The genetic architecture of human complex phenotypes is modulated by linkage disequilibrium and heterozygosity. Genetics. ISSN 0016-6731. 217(3), s. 1–21. doi: 10.1093/genetics/iyaa046.
• Torgersen, Kristin Stensland; Bahrami, Shahram; Frei, Oleksandr; Shadrin, Alexey; O'Connell, Kevin Sean & Smeland, Olav Bjerkehagen [Vis alle 10 forfattere av denne artikkelen] (2021). Shared genetic architecture between neuroticism, coronary artery disease and cardiovascular risk factors. Translational Psychiatry. ISSN 2158-3188. 11(1), s. 1–13. doi: 10.1038/s41398-021-01466-9. Fulltekst i vitenarkiv
• O'Connell, Kevin S.; Sønderby, Ida Elken; Frei, Oleksandr; van der Meer, Dennis; Athanasiu, Lavinia & Smeland, Olav Bjerkehagen [Vis alle 13 forfattere av denne artikkelen] (2021). Association between complement component 4A expression, cognitive performance and brain imaging measures in UK Biobank. Psychological Medicine. ISSN 0033-2917. s. 1–11. doi: 10.1017/S0033291721000179. Fulltekst i vitenarkiv
• Rødevand, Linn ; Bahrami, Shahram; Frei, Oleksandr; Chu, Yunhan; Shadrin, Alexey A. & O'Connell, Kevin Sean [Vis alle 14 forfattere av denne artikkelen] (2021). Extensive bidirectional genetic overlap between bipolar disorder and cardiovascular disease phenotypes. Translational Psychiatry. ISSN 2158-3188. 11. doi: 10.1038/s41398-021-01527-z. Fulltekst i vitenarkiv
• Cheng, Weiqiu; Frei, Oleksandr; van der Meer, Dennis; Wang, Yunpeng; O`Connell, Kevin & Chu, Yunhan [Vis alle 20 forfattere av denne artikkelen] (2021). Genetic Association Between Schizophrenia and Cortical Brain Surface Area and Thickness. JAMA psychiatry. ISSN 2168-6238. 78(9), s. 1020–1030. doi: 10.1001/jamapsychiatry.2021.1435. Fulltekst i vitenarkiv
• Gurholt, Tiril Pedersen; Kaufmann, Tobias; Frei, Oleksandr; Alnæs, Dag; Haukvik, Unn Kristin H. & van der Meer, Dennis [Vis alle 17 forfattere av denne artikkelen] (2021). Population-based body–brain mapping links brain morphology with anthropometrics and body composition. Translational Psychiatry. ISSN 2158-3188. doi: 10.1038/s41398-021-01414-7. Fulltekst i vitenarkiv
• Osete, Jordi Requena; Akkouh, Ibrahim; Reis de Assis, Denis; Szabo, Attila; Frei, Evgeniia & Hughes, Timothy [Vis alle 10 forfattere av denne artikkelen] (2021). Lithium increases mitochondrial respiration in iPSC-derived neural precursor cells from lithium responders. Molecular Psychiatry. ISSN 1359-4184. doi: 10.1038/s41380-021-01164-4. Fulltekst i vitenarkiv
• Dieset, Ingrid; Løvhaug, Lars; Selle, Morten Stefan; Kolseth, Asbjørn; Smeland, Olav Bjerkehagen & Færden, Ann (2021). Lessons learned from a cross-sectional survey among patients and staff in an acute psychiatric unit during an ongoing pandemic outbreak. Psychiatry Research. ISSN 0165-1781. 298, s. 1–3. doi: 10.1016/j.psychres.2021.113779. Fulltekst i vitenarkiv
• Bahrami, Shahram; Shadrin, Alexey A.; Frei, Oleksandr; O`Connell, Kevin; Bettella, Francesco & Krull, Florian [Vis alle 15 forfattere av denne artikkelen] (2021). Genetic loci shared between major depression and intelligence with mixed directions of effect. Nature Human Behaviour. ISSN 2397-3374. s. 1–9. doi: 10.1038/s41562-020-01031-2.
• Roelfs, Daniel; Alnæs, Dag; Frei, Oleksandr; van der Meer, Dennis; Smeland, Olav Bjerkehagen & Andreassen, Ole Andreas [Vis alle 8 forfattere av denne artikkelen] (2021). Phenotypically independent profiles relevant to mental health are genetically correlated. Translational Psychiatry. ISSN 2158-3188. 11(1). doi: 10.1038/s41398-021-01313-x. Fulltekst i vitenarkiv Vis sammendrag

  Genome-wide association studies (GWAS) and family-based studies have revealed partly overlapping genetic architectures between various psychiatric disorders. Given clinical overlap between disorders, our knowledge of the genetic architectures underlying specific symptom profiles and risk factors is limited. Here, we aimed to derive distinct profiles relevant to mental health in healthy individuals and to study how these genetically relate to each other and to common psychiatric disorders. Using independent component analysis, we decomposed self-report mental health questionnaires from 136,678 healthy individuals of the UK Biobank, excluding data from individuals with a diagnosed neurological or psychiatric disorder, into 13 distinct profiles relevant to mental health, capturing different symptoms as well as social and risk factors underlying reduced mental health. Utilizing genotypes from 117,611 of those individuals with White British ancestry, we performed GWAS for each mental health profile and assessed genetic correlations between these profiles, and between the profiles and common psychiatric disorders and cognitive traits. We found that mental health profiles were genetically correlated with a wide range of psychiatric disorders and cognitive traits, with strongest effects typically observed between a given mental health profile and a disorder for which the profile is common (e.g. depression symptoms and major depressive disorder, or psychosis and schizophrenia). Strikingly, although the profiles were phenotypically uncorrelated, many of them were genetically correlated with each other. This study provides evidence that statistically independent mental health profiles partly share genetic underpinnings and show genetic overlap with psychiatric disorders, suggesting that shared genetics across psychiatric disorders cannot be exclusively attributed to the known overlapping symptomatology between the disorders.

• Rødevand, Linn ; Bahrami, Shahram; Frei, Oleksandr; Lin, Aihua; Gani, Osman & Shadrin, Alexey A. [Vis alle 18 forfattere av denne artikkelen] (2021). Polygenic overlap and shared genetic loci between loneliness, severe mental disorders, and cardiovascular disease risk factors suggest shared molecular mechanisms. Translational Psychiatry. ISSN 2158-3188. 11(1). doi: 10.1038/s41398-020-01142-4. Fulltekst i vitenarkiv Vis sammendrag

  Clinical and epidemiological evidence suggest that loneliness is associated with severe mental disorders (SMDs) and increases the risk of cardiovascular disease (CVD). However, the mechanisms underlying the relationship between loneliness, SMDs, and CVD risk factors remain unknown. Here we explored overlapping genetic architecture and genetic loci shared between SMDs, loneliness, and CVD risk factors. We analyzed large independent genome-wide association study data on schizophrenia (SCZ), bipolar disorder (BD), major depression (MD), loneliness and CVD risk factors using bivariate causal mixture mode (MiXeR), which estimates the total amount of shared variants, and conditional false discovery rate to evaluate overlap in specific loci. We observed substantial genetic overlap between SMDs, loneliness and CVD risk factors, beyond genetic correlation. We identified 149 loci jointly associated with loneliness and SMDs (MD n = 67, SCZ n = 54, and BD n = 28), and 55 distinct loci jointly associated with loneliness and CVD risk factors. A total of 153 novel loneliness loci were found. Most of the shared loci possessed concordant effect directions, suggesting that genetic risk for loneliness may increase the risk of both SMDs and CVD. Functional analyses of the shared loci implicated biological processes related to the brain, metabolic processes, chromatin and immune system. Altogether, the study revealed polygenic overlap between loneliness, SMDs and CVD risk factors, providing new insights into their shared genetic architecture and common genetic mechanisms.

• Holland, Dominic; Frei, Oleksandr; Desikan, Rahul S.; Fan, Chun-Chieh; Shadrin, Alexey A. & Smeland, Olav Bjerkehagen [Vis alle 10 forfattere av denne artikkelen] (2020). Beyond SNP heritability: Polygenicity and discoverability of phenotypes estimated with a univariate Gaussian mixture model. PLoS Genetics. ISSN 1553-7390. doi: 10.1371/journal.pgen.1008612. Fulltekst i vitenarkiv
• Coleman, Jonathan R.I.; Gaspar, Helena A; Bryois, Julien; Byrne, Enda M; Forstner, Andreas J & Holmans, Peter A [Vis alle 51 forfattere av denne artikkelen] (2020). The Genetics of the Mood Disorder Spectrum: Genome-wide Association Analyses of More Than 185,000 Cases and 439,000 Controls. Biological Psychiatry. ISSN 0006-3223. doi: 10.1016/j.biopsych.2019.10.015. Vis sammendrag

  Background: Mood disorders (including major depressive disorder and bipolar disorder) affect 10% to 20% of the population. They range from brief, mild episodes to severe, incapacitating conditions that markedly impact lives. Multiple approaches have shown considerable sharing of risk factors across mood disorders despite their diagnostic distinction. Methods: To clarify the shared molecular genetic basis of major depressive disorder and bipolar disorder and to highlight disorder-specific associations, we meta-analyzed data from the latest Psychiatric Genomics Consortium genome-wide association studies of major depression (including data from 23andMe) and bipolar disorder, and an additional major depressive disorder cohort from UK Biobank (total: 185,285 cases, 439,741 controls; nonoverlapping N = 609,424). Results: Seventy-three loci reached genome-wide significance in the meta-analysis, including 15 that are novel for mood disorders. More loci from the Psychiatric Genomics Consortium analysis of major depression than from that for bipolar disorder reached genome-wide significance. Genetic correlations revealed that type 2 bipolar disorder correlates strongly with recurrent and single-episode major depressive disorder. Systems biology analyses highlight both similarities and differences between the mood disorders, particularly in the mouse brain cell types implicated by the expression patterns of associated genes. The mood disorders also differ in their genetic correlation with educational attainment-the relationship is positive in bipolar disorder but negative in major depressive disorder. Conclusions: The mood disorders share several genetic associations, and genetic studies of major depressive disorder and bipolar disorder can be combined effectively to enable the discovery of variants not identified by studying either disorder alone. However, we demonstrate several differences between these disorders. Analyzing subtypes of major depressive disorder and bipolar disorder provides evidence for a genetic mood disorders spectrum.

• Manchia, Mirko; Vieta, Eduard; Smeland, Olav Bjerkehagen; Altimus, Cara; Bechdolf, Andreas & Bellivier, Frank [Vis alle 29 forfattere av denne artikkelen] (2020). Translating big data to better treatment in bipolar disorder - a manifesto for coordinated action. European Neuropsychopharmacology. ISSN 0924-977X. 36, s. 121–136. doi: 10.1016/j.euroneuro.2020.05.006. Fulltekst i vitenarkiv
• Shadrin, Alexey A.; Frei, Oleksandr; Smeland, Olav Bjerkehagen; Bettella, Francesco; O`Connell, Kevin & Gani, Osman [Vis alle 12 forfattere av denne artikkelen] (2020). Phenotype-specific differences in polygenicity and effect size distribution across functional annotation categories revealed by AI-MiXeR. Bioinformatics. ISSN 1367-4803. doi: 10.1093/bioinformatics/btaa568. Fulltekst i vitenarkiv
• Engen, Magnus Johan; Lyngstad, Siv Hege; Ueland, Torill; Simonsen, Carmen Elisabeth; Vaskinn, Anja & Smeland, Olav Bjerkehagen [Vis alle 11 forfattere av denne artikkelen] (2020). Polygenic scores for schizophrenia and general cognitive ability: associations with six cognitive domains, premorbid intelligence, and cognitive composite score in individuals with a psychotic disorder and in healthy controls. Translational Psychiatry. ISSN 2158-3188. 10:416, s. 1–9. doi: 10.1038/s41398-020-01094-9. Fulltekst i vitenarkiv
• Còrdova Palomera, Aldo; van der Meer, Dennis; Kaufmann, Tobias; Bettella, Francesco; Wang, Yunpeng & Alnæs, Dag [Vis alle 40 forfattere av denne artikkelen] (2020). Genetic control of variability in subcortical and intracranial volumes. Molecular Psychiatry. ISSN 1359-4184. s. 1–8. doi: 10.1038/s41380-020-0664-1. Fulltekst i vitenarkiv
• van der Meer, Dennis; Frei, Oleksandr; Kaufmann, Tobias; Shadrin, Alexey A.; Devor, Anna & Smeland, Olav Bjerkehagen [Vis alle 12 forfattere av denne artikkelen] (2020). Understanding the genetic determinants of the brain with MOSTest. Nature Communications. ISSN 2041-1723. 11:3512, s. 1–9. doi: 10.1038/s41467-020-17368-1.
• Smeland, Olav Bjerkehagen; Shadrin, Alexey A.; Bahrami, Shahram; Broce, Iris J.; Tesli, Martin Steen & Frei, Oleksandr [Vis alle 22 forfattere av denne artikkelen] (2020). Genome-wide Association Analysis of Parkinson’s Disease and Schizophrenia Reveals Shared Genetic Architecture and Identifies Novel Risk Loci. Biological Psychiatry. ISSN 0006-3223. 89(3), s. 227–235. doi: 10.1016/j.biopsych.2020.01.026. Fulltekst i vitenarkiv Vis sammendrag

  BACKGROUND:Parkinson’s disease (PD) and schizophrenia (SCZ) are heritable brain disorders that involvedysregulation of the dopaminergic system. Epidemiological studies have reported potential comorbidity between thedisorders, and movement disturbances are common in patients with SCZ before treatment with antipsychotic drugs.Despite this, little is known about shared genetic etiology between the disorders.METHODS:We analyzed recent large genome-wide association studies on patients with SCZ (N= 77,096) and PD(N= 417,508) using a conditional/conjunctional false discovery rate (FDR) approach to evaluate overlap incommon genetic variants and improve statistical power for genetic discovery. Using a variety of biologicalresources, we functionally characterized the identified genomic loci.RESULTS:We observed genetic enrichment in PD conditional onassociations with SCZ and vice versa, indicatingpolygenic overlap. We then leveraged this cross-trait enrichment using conditional FDR analysis and identified 9 novel PDrisk loci and 1 novel SCZ locus at conditional FDR,.01. Furthermore, we identified 9 genomic loci jointly associated withPD and SCZ at conjunctional FDR,.05. There was an even distribution of antagonistic and agonistic effect directionsamong the shared loci, in line with the insignificant genetic correlation between the disorders. Of 67 genes mapped to theshared loci, 65 are expressed in the human brain and show cell type–specific expression profiles.CONCLUSIONS:Altogether, the study increases understanding of the genetic architectures underlying SCZ and PD,indicating that common molecular genetic mechanisms may contribute to overlapping pathophysiological and clinicalfeatures between the disorders.

• Smeland, Olav Bjerkehagen; Frei, Oleksandr; Dale, Anders & Andreassen, Ole Andreas (2020). The polygenic architecture of schizophrenia — rethinking pathogenesis and nosology. Nature Reviews Neurology. ISSN 1759-4758. s. 1–14. doi: 10.1038/s41582-020-0364-0.
• Bahrami, Shahram; Steen, Nils Eiel; Shadrin, Alexey A.; O`Connell, Kevin; Frei, Oleksandr & Bettella, Francesco [Vis alle 13 forfattere av denne artikkelen] (2020). Shared genetic loci between body mass index and major psychiatric disorders: A genome-wide association study. JAMA psychiatry. ISSN 2168-6238. 77(5), s. 503–512. doi: 10.1001/jamapsychiatry.2019.4188. Vis sammendrag

  IMPORTANCE People with major psychiatric disorders (MPDs) have a 10- to 20-year shorter life span than the rest of the population, and this difference is mainly due to comorbid cardiovascular diseases. Genome-wide association studies have identified common variants involved in schizophrenia (SCZ), bipolar disorder (BIP), and major depression (MD) and body mass index (BMI), a key cardiometabolic risk factor. However, genetic variants jointly influencing MPD and BMI remain largely unknown. OBJECTIVE To assess the extent of the overlap between the genetic architectures of MPDs and BMI and identify genetic loci shared between them. DESIGN, SETTING, AND PARTICIPANTS Using a conditional false discovery rate statistical framework, independent genome-wide association study data on individuals with SCZ (n = 82 315), BIP (n = 51 710), MD (n = 480 359), and BMI (n = 795 640) were analyzed. The UK Biobank cohort (n = 29 740) was excluded from the MD data set to avoid sample overlap. Data were collected from August 2017 to May 2018, and analysis began July 2018. MAIN OUTCOMES AND MEASURES The primary outcomes were a list of genetic loci shared between BMI and MPDs and their functional pathways. RESULTS Genome-wide association study data from 1 380 284 participants were analyzed, and the genetic correlation between BMI and MPDs varied (SCZ: r for genetic = −0.11, P = 2.1 × 10−10; BIP: r for genetic = −0.06, P = .0103; MD: r for genetic = 0.12, P = 6.7 × 10−10). Overall, 63, 17, and 32 loci shared between BMI and SCZ, BIP, and MD, respectively, were analyzed at conjunctional false discovery rate less than 0.01. Of the shared loci, 34% (73 of 213) in SCZ, 52% (36 of 69) in BIP, and 57% (56 of 99) in MD had risk alleles associated with higher BMI (conjunctional false discovery rate <0.05), while the rest had opposite directions of associations. Functional analyses indicated that the overlapping loci are involved in several pathways including neurodevelopment, neurotransmitter signaling, and intracellular processes, and the loci with concordant and opposite association directions pointed mostly to different pathways. CONCLUSIONS AND RELEVANCE In this genome-wide association study, extensive polygenic overlap between BMI and SCZ, BIP, and MD were found, and 111 shared genetic loci were identified, implicating novel functional mechanisms. There was mixture of association directions in SCZ and BMI, albeit with a preponderance of discordant ones

• Lee, Phil H.; Antilla, Verneri; Won, Hyejung; Feng, Yen-Chen A.; Rosenthal, Jacob & Zhu, Zhaozhong [Vis alle 66 forfattere av denne artikkelen] (2019). Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders. Cell. ISSN 0092-8674. 179(7), s. 1469–1482. doi: 10.1016/j.cell.2019.11.020. Fulltekst i vitenarkiv
• O`Connell, Kevin; Shadrin, Alexey A.; Smeland, Olav Bjerkehagen; Bahrami, Shahram; Frei, Oleksandr & Bettella, Francesco [Vis alle 24 forfattere av denne artikkelen] (2019). Identification of genetic loci shared between ADHD, intelligence and educational attainment . Biological Psychiatry. ISSN 0006-3223. 87(12), s. 1052–1062. doi: 10.1016/j.biopsych.2019.11.015. Fulltekst i vitenarkiv
• O`Connell, Kevin; Shadrin, Alexey A.; Bahrami, Shahram; Smeland, Olav Bjerkehagen; Bettella, Francesco & Frei, Oleksandr [Vis alle 20 forfattere av denne artikkelen] (2019). Identification of genetic overlap and novel risk loci for attention-deficit/hyperactivity disorder and bipolar disorder. Molecular Psychiatry. ISSN 1359-4184. s. 1–11. doi: 10.1038/s41380-019-0613-z. Fulltekst i vitenarkiv Vis sammendrag

  Differential diagnosis between childhood onset attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BD) remains a challenge, mainly due to overlapping symptoms and high rates of comorbidity. Despite this, genetic correlation reported for these disorders is low and non-significant. Here we aimed to better characterize the genetic architecture of these disorders utilizing recent large genome-wide association studies (GWAS). We analyzed independent GWAS summary statistics for ADHD (19,099 cases and 34,194 controls) and BD (20,352 cases and 31,358 controls) applying the conditional/conjunctional false discovery rate (condFDR/conjFDR) statistical framework that increases the power to detect novel phenotype-specific and shared loci by leveraging the combined power of two GWAS. We observed cross-trait polygenic enrichment for ADHD conditioned on associations with BD, and vice versa. Leveraging this enrichment, we identified 19 novel ADHD risk loci and 40 novel BD risk loci at condFDR <0.05. Further, we identified five loci jointly associated with ADHD and BD (conjFDR < 0.05). Interestingly, these five loci show concordant directions of effect for ADHD and BD. These results highlight a shared underlying genetic risk for ADHD and BD which may help to explain the high comorbidity rates and difficulties in differentiating between ADHD and BD in the clinic. Improving our understanding of the underlying genetic architecture of these disorders may aid in the development of novel stratification tools to help reduce these diagnostic difficulties.

• Mullins, Niamh; Bigdeli, Tim B.; Børglum, Anders D.; Coleman, Jonathan R.I.; Demontis, Ditte & Mehta, Divya [Vis alle 117 forfattere av denne artikkelen] (2019). GWAS of suicide attempt in psychiatric disorders and association with major depression polygenic risk scores. American Journal of Psychiatry. ISSN 0002-953X. 176(8), s. 651–660. doi: 10.1176/appi.ajp.2019.18080957. Fulltekst i vitenarkiv
• Alnæs, Dag; Kaufmann, Tobias; van der Meer, Dennis; Còrdova Palomera, Aldo; Rokicki, Jaroslav & Moberget, Torgeir [Vis alle 30 forfattere av denne artikkelen] (2019). Brain heterogeneity in schizophrenia and its association with polygenic risk. JAMA psychiatry. ISSN 2168-6238. 76(7), s. 739–748. doi: 10.1001/jamapsychiatry.2019.0257.
• Smeland, Olav Bjerkehagen; Frei, Oleksandr; Shadrin, Alexey A.; O`Connell, Kevin; Fan, Chun Chieh & Bahrami, Shahram [Vis alle 11 forfattere av denne artikkelen] (2019). Discovery of shared genomic loci using the conditional false discovery rate approach. Human Genetics. ISSN 0340-6717. s. 1–10. doi: 10.1007/s00439-019-02060-2. Fulltekst i vitenarkiv
• Smeland, Olav Bjerkehagen; Frei, Oleksandr; Fan, Chun-Chieh; Shadrin, Alexey A.; Dale, Anders & Andreassen, Ole Andreas (2019). The emerging pattern of shared polygenic architecture of psychiatric disorders, conceptual and methodological challenges. Psychiatric Genetics. ISSN 0955-8829. 29(5), s. 152–159. doi: 10.1097/YPG.0000000000000234. Fulltekst i vitenarkiv Vis sammendrag

  Genome-wide association studies have transformed psychiatric genetics and provided novel insights into the genetic etiology of psychiatric disorders. Two major discoveries have emerged; the disorders are polygenic, with a large number of common variants each with a small effect and many genetic variants influence more than one phenotype, suggesting shared genetic etiology. These concepts have the potential to revolutionize the current classification system with diagnostic categories and facilitate development of better treatments. However, to reach clinical impact, we need larger samples and better analytical tools, as most polygenic factors remain undetected. We here present statistical approaches designed to improve the yield of existing genome-wide association studies for polygenic phenotypes. We review how these tools have informed the current knowledge on the genetic architecture of psychiatric disorders, focusing on schizophrenia, bipolar disorder and major depression, and overlap with psychological and cognitive traits. We discuss application of statistical tools for stratification and prediction.

• Kaufmann, Tobias; van der Meer, Dennis; Doan, Nhat Trung; Schwarz, Emanuel; Lund, Martina Jonette & Agartz, Ingrid [Vis alle 84 forfattere av denne artikkelen] (2019). Common brain disorders are associated with heritable patterns of apparent aging of the brain. Nature Neuroscience. ISSN 1097-6256. 22(10), s. 1617–1623. doi: 10.1038/s41593-019-0471-7. Fulltekst i vitenarkiv
• Stahl, Eli A.; Breen, Gerome; Forstner, Andreas J.; McQuillin, Andrew; Ripke, Stephan & Trubetskoy, Vassily [Vis alle 277 forfattere av denne artikkelen] (2019). Genome-wide association study identifies 30 loci associated with bipolar disorder. Nature Genetics. ISSN 1061-4036. 51(5), s. 793–803. doi: 10.1038/s41588-019-0397-8. Fulltekst i vitenarkiv
• Frei, Oleksandr; Holland, Dominic; Smeland, Olav Bjerkehagen; Shadrin, Alexey A.; Fan, Chun Chieh & Mæland, Steffen [Vis alle 12 forfattere av denne artikkelen] (2019). Bivariate causal mixture model quantifies polygenic overlap between complex traits beyond genetic correlation. Nature Communications. ISSN 2041-1723. 10(1). doi: 10.1038/s41467-019-10310-0. Fulltekst i vitenarkiv
• Steen, Nils Eiel; Dieset, Ingrid; Hope, Sigrun; Vedal, Trude Seselie Jahr; Smeland, Olav Bjerkehagen & Matson, Wayne [Vis alle 13 forfattere av denne artikkelen] (2019). Metabolic dysfunctions in the kynurenine pathway, noradrenergic and purine metabolism in schizophrenia and bipolar disorders. Psychological Medicine. ISSN 0033-2917. 17(2). doi: 10.1017/S0033291719000400. Fulltekst i vitenarkiv
• Drange, Ole Kristian; Smeland, Olav Bjerkehagen; Shadrin, Alexey A.; Finseth, Per Ivar; Witoelar, Aree & Frei, Oleksandr [Vis alle 52 forfattere av denne artikkelen] (2019). Genetic Overlap Between Alzheimer’s Disease and Bipolar Disorder Implicates the MARK2 and VAC14 Genes. Frontiers in Neuroscience. ISSN 1662-4548. 13. doi: 10.3389/fnins.2019.00220. Fulltekst i vitenarkiv Vis sammendrag

  Background: Alzheimer’s disease (AD) and bipolar disorder (BIP) are complex traits influenced by numerous common genetic variants, most of which remain to be detected. Clinical and epidemiological evidence suggest that AD and BIP are related. However, it is not established if this relation is of genetic origin. Here, we applied statistical methods based on the conditional false discovery rate (FDR) framework to detect genetic overlap between AD and BIP and utilized this overlap to increase the power to identify common genetic variants associated with either or both traits. Methods: We obtained genome wide association studies data from the International Genomics of Alzheimer’s Project part 1 (17,008 AD cases and 37,154 controls) and the Psychiatric Genetic Consortium Bipolar Disorder Working Group (20,352 BIP cases and 31,358 controls). We used conditional QQ-plots to assess overlap in common genetic variants between AD and BIP. We exploited the genetic overlap to re-rank test-statistics for AD and BIP and improve detection of genetic variants using the conditional FDR framework. Results: Conditional QQ-plots demonstrated a polygenic overlap between AD and BIP. Using conditional FDR, we identified one novel genomic locus associated with AD, and nine novel loci associated with BIP. Further, we identified two novel loci jointly associated with AD and BIP implicating the MARK2 gene (lead SNP rs10792421, conjunctional FDR = 0.030, same direction of effect) and the VAC14 gene (lead SNP rs11649476, conjunctional FDR = 0.022, opposite direction of effect). Conclusion: We found polygenic overlap between AD and BIP and identified novel loci for each trait and two jointly associated loci. Further studies should examine if the shared loci implicating the MARK2 and VAC14 genes could explain parts of the shared and distinct features of AD and BIP.

• Smeland, Olav Bjerkehagen; Bahrami, Shahram; Frei, Oleksandr; Shadrin, Alexey A.; O`Connell, Kevin & Savage, Jeanne E. [Vis alle 15 forfattere av denne artikkelen] (2019). Genome-wide analysis reveals extensive genetic overlap between schizophrenia, bipolar disorder, and intelligence. Molecular Psychiatry. ISSN 1359-4184. s. 1–10. doi: 10.1038/s41380-018-0332-x. Fulltekst i vitenarkiv
• Psychiatric Genomics Consorti, Bipolar Sczhizophrenia; Ruderfer, Douglas M.; Ripke, Stephan; McQuillin, Andrew; Boocock, James & Stahl, Eli A. [Vis alle 52 forfattere av denne artikkelen] (2018). Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes. Cell. ISSN 0092-8674. 173(7), s. 1705–1715. doi: 10.1016/j.cell.2018.05.046.
• Bettella, Francesco; Brown, AA; Smeland, Olav Bjerkehagen; Wang, Yunpeng; Witoelar, Aree & Buil Demur, AA [Vis alle 11 forfattere av denne artikkelen] (2018). Cross-tissue eQTL enrichment of associations in schizophrenia. PLOS ONE. ISSN 1932-6203. 13(9). doi: 10.1371/journal.pone.0202812. Fulltekst i vitenarkiv
• Karch, Celeste M.; Wen, Natalie; Fan, Chun C.; Yokoyama, Jennifer S.; Kouri, Naomi & Ross, Owen A. [Vis alle 21 forfattere av denne artikkelen] (2018). Selective genetic overlap between amyotrophic lateral sclerosis and diseases of the frontotemporal dementia spectrum. JAMA Neurology. ISSN 2168-6149. 75(7), s. 860–875. doi: 10.1001/jamaneurol.2018.0372.
• van der Meer, Dennis; Rokicki, Jaroslav; Kaufmann, Tobias; Còrdova Palomera, Aldo; Moberget, Torgeir & Alnæs, Dag [Vis alle 54 forfattere av denne artikkelen] (2018). Brain scans from 21,297 individuals reveal the genetic architecture of hippocampal subfield volumes. Molecular Psychiatry. ISSN 1359-4184. s. 1–13. doi: 10.1038/s41380-018-0262-7. Fulltekst i vitenarkiv
• Srinivasan, Saurabh; Bettella, Francesco; Frei, Oleksandr; Hill, W. David; Wang, Yunpeng & Witoelar, Aree [Vis alle 17 forfattere av denne artikkelen] (2018). Enrichment of genetic markers of recent human evolution in educational and cognitive traits. Scientific Reports. ISSN 2045-2322. 8:12585, s. 1–9. doi: 10.1038/s41598-018-30387-9. Fulltekst i vitenarkiv
• Fan, Chun Chieh; Smeland, Olav Bjerkehagen; Schork, Andrew J.; Chen, Chi-Hua; Holland, Dominic & Lo, Min-Tzu [Vis alle 11 forfattere av denne artikkelen] (2018). Beyond heritability: Improving discoverability in imaging genetics. Human Molecular Genetics. ISSN 0964-6906. 27(1), s. R22–R28. doi: 10.1093/hmg/ddy082.
• Savage, Jeanne E.; Jansen, Philip R.; Stringer, Sven; Watanabe, Kyoko; Bryois, Julien & de Leeuw, Christiaan A. [Vis alle 117 forfattere av denne artikkelen] (2018). Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence. Nature Genetics. ISSN 1061-4036. 50, s. 912–919. doi: 10.1038/s41588-018-0152-6.
• Zuber, Verena; Jönsson, Erik Gunnar; Frei, Oleksandr; Witoelar, Aree; Thompson, Wesley Kurt & Schork, Andrew J. [Vis alle 18 forfattere av denne artikkelen] (2018). Identification of shared genetic variants between schizophrenia and lung cancer. Scientific Reports. ISSN 2045-2322. 674(8), s. 1–8. doi: 10.1038/s41598-017-16481-4. Fulltekst i vitenarkiv
• Smeland, Olav Bjerkehagen & Andreassen, Ole Andreas (2018). How can genetics help understand the relationship between cognitive dysfunction and schizophrenia? Scandinavian Journal of Psychology. ISSN 0036-5564. 59(1), s. 26–31. doi: 10.1111/sjop.12407.
• Shadrin, Alexey A.; Smeland, Olav Bjerkehagen; Zayats, Tetyana; Schork, Andrew J; Frei, Oleksandr & Bettella, Francesco [Vis alle 19 forfattere av denne artikkelen] (2017). Novel loci associated with attention-deficit/hyperactivity disorder are revealed by leveraging polygenic overlap with educational attainment. Journal of the American Academy of Child and Adolescent Psychiatry. ISSN 0890-8567. 57(2), s. 86–95. doi: 10.1016/j.jaac.2017.11.013. Fulltekst i vitenarkiv

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• Hindley, Guy; Drange, Ole Kristian; Lin, Aihua; Kutrolli, Gleda; Shadrin, Alexey & Parker, Nadine [Vis alle 20 forfattere av denne artikkelen] (2024). Corrigendum to “Cross-trait genome-wide association analysis of C-reactive protein level and psychiatric disorders” [Psychoneuroendocrinology 157 (2023) 106368] (Psychoneuroendocrinology (2023) 157, (S0306453023003463), (10.1016/j.psyneuen.2023.106368)). Psychoneuroendocrinology. ISSN 0306-4530. doi: 10.1016/j.psyneuen.2024.106980.
• Birkenæs, Viktoria; Shadrin, Alexey; Frei, Evgeniia; Parekh, Pravesh; Jaholkowski, Piotr Pawel & Smeland, Olav Bjerkehagen [Vis alle 9 forfattere av denne artikkelen] (2023). Genome-Wide Analysis of Self-Reported Psychotic Experiences in the Norwegian Mother, Father, and Child study.
• Van Assche, Evelien; Schulte, Eva C.; Andreassen, Ole; Smeland, Olav Bjerkehagen & Luykx, Jurjen J. (2022). Editorial: Cross-disorder Genetics in Neuropsychiatry. Frontiers in Neuroscience. ISSN 1662-4548. 16. doi: 10.3389/fnins.2022.826300.
• van der Meer, Dennis; Frei, Oleksandr; Kaufmann, Tobias; Shadrin, Alexey; Devor, Anna & Smeland, Olav Bjerkehagen [Vis alle 12 forfattere av denne artikkelen] (2020). Author Correction: Understanding the genetic determinants of the brain with MOSTest (Nature Communications, (2020), 11, 1, (3512), 10.1038/s41467-020-17368-1). Nature Communications. ISSN 2041-1723. 11(1). doi: 10.1038/s41467-020-18628-w.
• Kaufmann, Tobias; van der Meer, Dennis; Doan, Nhat Trung; Schwarz, Emanuel; Lund, Martina Jonette & Agartz, Ingrid [Vis alle 97 forfattere av denne artikkelen] (2020). Publisher Correction: Common brain disorders are associated with heritable patterns of apparent aging of the brain (Nature Neuroscience, (2019), 22, 10, (1617-1623), 10.1038/s41593-019-0471-7). Nature Neuroscience. ISSN 1097-6256. 23(2). doi: 10.1038/s41593-019-0553-6.
• Smeland, Olav Bjerkehagen; Bahrami, Shahram; Frei, Oleksandr; Shadrin, Alexey; O'Connell, Kevin & Savage, Jeanne [Vis alle 15 forfattere av denne artikkelen] (2019). Correction: Genome-wide analysis reveals extensive genetic overlap between schizophrenia, bipolar disorder, and intelligence (Molecular Psychiatry, (2020), 25, 4, (844-853), 10.1038/s41380-018-0332-x). Molecular Psychiatry. ISSN 1359-4184. 25(4), s. 914–914. doi: 10.1038/s41380-019-0456-7.
• Smeland, Olav Bjerkehagen; Bahrami, Shahram; Frei, Oleksandr; Shadrin, Alexey A.; Savage, Jeanne E. & Watanabe, Kyoko [Vis alle 14 forfattere av denne artikkelen] (2018). Genome-wide analysis reveals extensive genetic overlap between schizophrenia, bipolar disorder and intelligence .

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