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Cited by 48Genetic Associations and EpidemiologySchizophrenia research and treatmentMental Health Research Topics

Genetic and phenotypic similarity across major psychiatric disorders: a systematic review and quantitative assessment

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Bourque, Vincent-Raphael, Poulain, Cécile, Proulx, Catherine, Moreau, Clara A., Joober, Ridha, Forgeot d’Arc, Baudouin, Huguet, Guillaume, Jacquemont, Sébastien·2024·Translational Psychiatry
DOI 10.1038/s41398-024-02866-3PMC PMC10981737
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Abstract

There is widespread overlap across major psychiatric disorders, and this is the case at different levels of observations, from genetic variants to brain structures and function and to symptoms. However, it remains unknown to what extent these commonalities at different levels of observation map onto each other. Here, we systematically review and compare the degree of similarity between psychiatric disorders at all available levels of observation. We searched PubMed and EMBASE between January 1, 2009 and September 8, 2022. We included original studies comparing at least four of the following five diagnostic groups: Schizophrenia, Bipolar Disorder, Major Depressive Disorder, Autism Spectrum Disorder, and Attention Deficit Hyperactivity Disorder, with measures of similarities between all disorder pairs. Data extraction and synthesis were performed by two independent researchers, following the PRISMA guidelines. As main outcome measure, we assessed the Pearson correlation measuring the degree of similarity across disorders pairs between studies and biological levels of observation. We identified 2975 studies, of which 28 were eligible for analysis, featuring similarity measures based on single-nucleotide polymorphisms, gene-based analyses, gene expression, structural and functional connectivity neuroimaging measures. The majority of correlations (88.6%) across disorders between studies, within and between levels of observation, were positive. To identify a consensus ranking of similarities between disorders, we performed a principal component analysis. Its first dimension explained 51.4% (95% CI: 43.2, 65.4) of the variance in disorder similarities across studies and levels of observation. Based on levels of genetic correlation, we estimated the probability of another psychiatric diagnosis in first-degree relatives and showed that they were systematically lower than those observed in population studies. Our findings highlight that genetic and brain factors may underlie a large proportion, but not all of the diagnostic overlaps observed in the clinic.

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  • Neurological diseases share symptomatic and molecular changes including memory loss and protein aggregation in various dementia types and genetic overlap and comorbidity across psychiatric disorders.

    “Neurological diseases share symptomatic and molecular changes including memory loss and protein aggregation in various dementia types (17) and genetic overlap and comorbidity across psychiatric disorders (18).”

    From Low overlap of plasma and CSF protein quantitative trait loci affects protein discovery for neurological disease (2026) · cites this paper as [18]

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  1. [2]Brainstorm Consortium, Anttila V, Bulik-Sullivan B, Finucane HK, Walters RK, Bras J et al. Analysis of shared heritability in common disorders of the brain. Science. 2018;360. PMC6097237 29930110
  2. [3]Lee PH Feng Y-CA Smoller JW Pleiotropy and cross-disorder genetics among psychiatric disorders Biol Psychiatry 2021 89 20 31 10.1016/j.biopsych.2020.09.026 33131714 PMC7898275 · DOI
  3. [4]Hettwer MD Larivière S Park BY van den Heuvel OA Schmaal L Andreassen OA Coordinated cortical thickness alterations across six neurodevelopmental and psychiatric disorders Nat Commun 2022 13 6851 10.1038/s41467-022-34367-6 36369423 PMC9652311 · DOI
  4. [5]Moreau CA Urchs SGW Kuldeep K Orban P Schramm C Dumas G Mutations associated with neuropsychiatric conditions delineate functional brain connectivity dimensions contributing to autism and schizophrenia Nat Commun 2020 11 5272 10.1038/s41467-020-18997-2 33077750 PMC7573583 · DOI
  5. [6]Gandal MJ Haney JR Parikshak NN Leppa V Ramaswami G Hartl C Shared molecular neuropathology across major psychiatric disorders parallels polygenic overlap Focus 2019 17 66 72 10.1176/appi.focus.17103 32015716 PMC6996074 · DOI
  6. [7]Opel N Goltermann J Hermesdorf M Berger K Baune BT Dannlowski U Cross-disorder analysis of brain structural abnormalities in six major psychiatric disorders: a secondary analysis of mega- and meta-analytical findings from the ENIGMA Consortium Biol Psychiatry 2020 88 678 86 10.1016/j.biopsych.2020.04.027 32646651 · DOI
  7. [8]Patel Y Parker N Shin J Howard D French L Thomopoulos SI Virtual histology of cortical thickness and shared neurobiology in 6 psychiatric disorders JAMA Psychiatry 2021 78 47 63 10.1001/jamapsychiatry.2020.2694 32857118 PMC7450410 · DOI
  8. [9]Moreau CA Kumar K Harvey A Huguet G Urchs SGW Schultz LM Brain functional connectivity mirrors genetic pleiotropy in psychiatric conditions Brain 2023 146 1686 96 10.1093/brain/awac315 36059063 PMC10319760 · DOI
  9. [10]Pettersson E Larsson H Lichtenstein P Common psychiatric disorders share the same genetic origin: a multivariate sibling study of the Swedish population Mol Psychiatry 2016 21 717 21 10.1038/mp.2015.116 26303662 · DOI · Paper page
  10. [11]Kendler KS Ohlsson H Sundquist J Sundquist K Family Genetic Risk Scores and the genetic architecture of major affective and psychotic disorders in a Swedish National Sample JAMA Psychiatry 2021 78 735 43 10.1001/jamapsychiatry.2021.0336 33881469 PMC8060884 · DOI
  11. [12]Ligthart L Boomsma DI Causes of comorbidity: pleiotropy or causality? Shared genetic and environmental influences on migraine and neuroticism Twin Res Hum Genet 2012 15 158 65 10.1375/twin.15.2.158 22856357 · DOI
  12. [13]Plana-Ripoll O Pedersen CB Holtz Y Benros ME Dalsgaard S de Jonge P Exploring comorbidity within mental disorders among a Danish national population JAMA Psychiatry 2019 76 259 70 10.1001/jamapsychiatry.2018.3658 30649197 PMC6439836 · DOI · Paper page
  13. [15]Weye N Santomauro DF Agerbo E Christensen MK Iburg KM Momen NC Register-based metrics of years lived with disability associated with mental and substance use disorders: a register-based cohort study in Denmark Lancet Psychiatry 2021 8 310 9 10.1016/S2215-0366(21)00029-8 33743882 · DOI
  14. [16]Malla A McGorry P Early intervention in psychosis in young people: a population and public health perspective Am J Public Health 2019 109 S181 S184 10.2105/AJPH.2019.305018 31242015 PMC6595512 · DOI
  15. [17]Correll CU Cortese S Croatto G Monaco F Krinitski D Arrondo G Efficacy and acceptability of pharmacological, psychosocial, and brain stimulation interventions in children and adolescents with mental disorders: an umbrella review World Psychiatry 2021 20 244 75 10.1002/wps.20881 34002501 PMC8129843 · DOI
  16. [22]Radonjić NV Hess JL Rovira P Andreassen O Buitelaar JK Ching CRK Structural brain imaging studies offer clues about the effects of the shared genetic etiology among neuropsychiatric disorders Mol Psychiatry 2021 26 2101 10 10.1038/s41380-020-01002-z 33456050 PMC8440178 · DOI
  17. [23]Josse J Husson F missMDA: a package for handling missing values in multivariate data analysis J Stat Softw 2016 70 1 31 10.18637/jss.v070.i01 · DOI
  18. [24]Lê S Josse J Husson F FactoMineR: an R package for multivariate analysis J Stat Softw 2008 25 18 10.18637/jss.v025.i01 · DOI
  19. [25]Davison AC Hinkley DV Bootstrap methods and their application 1997 Cambridge University Press
  20. [26]Falconer DS The inheritance of liability to certain diseases, estimated from the incidence among relatives Ann Hum Genet 1965 29 51 76 10.1111/j.1469-1809.1965.tb00500.x · DOI
  21. [27]Baselmans BML Yengo L van Rheenen W Wray NR Risk in relatives, heritability, SNP-based heritability, and genetic correlations in psychiatric disorders: a review Biol Psychiatry 2021 89 11 19 10.1016/j.biopsych.2020.05.034 32736793 · DOI · Paper page
  22. [28]Pedersen CB Mors O Bertelsen A Waltoft BL Agerbo E McGrath JJ A comprehensive nationwide study of the incidence rate and lifetime risk for treated mental disorders JAMA Psychiatry 2014 71 573 81 10.1001/jamapsychiatry.2014.16 24806211 · DOI
  23. [29]Cheng C-M Chang W-H Chen M-H Tsai C-F Su T-P Li C-T Co-aggregation of major psychiatric disorders in individuals with first-degree relatives with schizophrenia: a nationwide population-based study Mol Psychiatry 2018 23 1756 63 10.1038/mp.2017.217 29112198 · DOI
  24. [30]Wang HE Cheng C-M Bai Y-M Hsu J-W Huang K-L Su T-P Familial coaggregation of major psychiatric disorders in first-degree relatives of individuals with autism spectrum disorder: a nationwide population-based study Psychol Med 2022 52 1437 47 10.1017/S0033291720003207 32914742 · DOI
  25. [32]Chen M-H Pan T-L Huang K-L Hsu J-W Bai Y-M Su T-P Coaggregation of major psychiatric disorders in first-degree relatives of individuals with attention-deficit/hyperactivity disorder: a nationwide population-based study J Clin Psychiatry 2019 80 11619. 10.4088/JCP.18m12371 31090279 · DOI
  26. [33]Schork AJ Won H Appadurai V Nudel R Gandal M Delaneau O A genome-wide association study of shared risk across psychiatric disorders implicates gene regulation during fetal neurodevelopment Nat Neurosci 2019 22 353 361 10.1038/s41593-018-0320-0 30692689 PMC6497521 · DOI · Paper page
  27. [34]Selzam S Coleman JRI Caspi A Moffitt TE Plomin R A polygenic p factor for major psychiatric disorders Transl Psychiatry 2018 8 205. 10.1038/s41398-018-0217-4 30279410 PMC6168558 · DOI
  28. [35]Lin LI A concordance correlation coefficient to evaluate reproducibility Biometrics 1989 45 255 68 10.2307/2532051 2720055 · DOI · Paper page
  29. [36]Bipolar Disorder and Schizophrenia Working Group of the Psychiatric Genomics Consortium. Electronic address: douglas.ruderfer@vanderbilt.edu, Bipolar Disorder and Schizophrenia Working Group of the Psychiatric Genomics Consortium. Genomic dissection of bipolar disorder and schizophrenia, including 28 subphenotypes Cell 2018 173 1705 1715.e16 10.1016/j.cell.2018.05.046 29906448 PMC6432650 · DOI
  30. [38]Plana-Ripoll O Musliner KL Dalsgaard S Momen NC Weye N Christensen MK Nature and prevalence of combinations of mental disorders and their association with excess mortality in a population-based cohort study World Psychiatry 2020 19 339 349 10.1002/wps.20802 32931098 PMC7491620 · DOI
  31. [39]Sánchez XC Helenius D Bybjerg-Grauholm J Pedersen C Hougaard DM Børglum AD Comparing copy number variations in a Danish case cohort of individuals with psychiatric disorders JAMA Psychiatry 2022 79 59 69 10.1001/jamapsychiatry.2021.3392 34817560 PMC8733851 · DOI
  32. [40]Kushima I Nakatochi M Aleksic B Okada T Kimura H Kato H Cross-disorder analysis of genic and regulatory copy number variations in bipolar disorder, schizophrenia, and autism spectrum disorder Biol Psychiatry 2022 92 362 374 10.1016/j.biopsych.2022.04.003 35667888 · DOI
  33. [41]Arango C Dragioti E Solmi M Cortese S Domschke K Murray RM Risk and protective factors for mental disorders beyond genetics: an evidence-based atlas World Psychiatry 2021 20 417 436 10.1002/wps.20894 34505386 PMC8429329 · DOI
  34. [42]Warrier V Kwong ASF Luo M Dalvie S Croft J Sallis HM Gene–environment correlations and causal effects of childhood maltreatment on physical and mental health: a genetically informed approach Lancet Psychiatry 2021 8 373 386 10.1016/S2215-0366(20)30569-1 33740410 PMC8055541 · DOI · Paper page
  35. [43]Leppert B Millard LAC Riglin L Davey Smith G Thapar A Tilling K A cross-disorder PRS-pheWAS of 5 major psychiatric disorders in UK Biobank PLoS Genet 2020 16 e1008185 10.1371/journal.pgen.1008185 32392212 PMC7274459 · DOI
  36. [44]Lin BD Pries L-K Sarac HS van Os J Rutten BPF Luykx J Nongenetic factors associated with psychotic experiences among UK biobank participants: exposome-wide analysis and Mendelian randomization analysis JAMA Psychiatry 2022 79 857 868 10.1001/jamapsychiatry.2022.1655 35857297 PMC9301596 · DOI
  37. [46]Warrington NM Hwang L-D Nivard MG Evans DM Estimating direct and indirect genetic effects on offspring phenotypes using genome-wide summary results data Nat Commun 2021 12 5420 10.1038/s41467-021-25723-z 34521848 PMC8440517 · DOI
  38. [47]Raznahan A Won H Glahn DC Jacquemont S Convergence and divergence of rare genetic disorders on brain phenotypes: a review JAMA Psychiatry 2022 79 818 828 10.1001/jamapsychiatry.2022.1450 35767289 · DOI
  39. [48]Kopal J Kumar K Saltoun K Modenato C Moreau CA Martin-Brevet S Rare CNVs and phenome-wide profiling highlight brain structural divergence and phenotypical convergence Nat Hum Behav 2023 7 1001 1017 10.1038/s41562-023-01541-9 36864136 PMC7615290 · DOI
  40. [49]Kendler KS Chatzinakos C Bacanu S-A The impact on estimations of genetic correlations by the use of super-normal, unscreened, and family-history screened controls in genome wide case-control studies Genet Epidemiol 2020 44 283 289 10.1002/gepi.22281 31961015 · DOI
  41. [51]Doherty JL Owen MJ Genomic insights into the overlap between psychiatric disorders: implications for research and clinical practice Genome Med 2014 6 29 10.1186/gm546 24944580 PMC4062063 · DOI · Paper page
  42. [52]Pacheco J Garvey MA Sarampote CS Cohen ED Murphy ER Friedman-Hill SR Annual Research Review: the contributions of the RDoC research framework on understanding the neurodevelopmental origins, progression and treatment of mental illnesses J Child Psychol Psychiatry 2022 63 360 376 10.1111/jcpp.13543 34979592 PMC8940667 · DOI
  43. [53]Kotov R Krueger RF Watson D A paradigm shift in psychiatric classification: the Hierarchical Taxonomy Of Psychopathology (HiTOP) World Psychiatry 2018 17 24 25 10.1002/wps.20478 29352543 PMC5775140 · DOI
  44. [54]Lee SH Ripke S Neale BM Faraone SV Purcell SM Perlis RH Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs Nat Genet 2013 45 984 994 10.1038/ng.2711 23933821 PMC3800159 · DOI · Paper page
  45. [56]Grotzinger AD Mallard TT Akingbuwa WA Ip HF Adams MJ Lewis CM Genetic architecture of 11 major psychiatric disorders at biobehavioral, functional genomic and molecular genetic levels of analysis Nat Genet 2022 54 548 559 10.1038/s41588-022-01057-4 35513722 PMC9117465 · DOI
  46. [57]Li Z Li D He Y Wang K Ma X Chen X Cross-Disorder Analysis of Shared Genetic Components Between Cortical Structures and Major Psychiatric Disorders Schizophr Bull 2022 48 1145 1154 10.1093/schbul/sbac019 35265999 PMC9434450 · DOI
  47. [58]Gerring ZF Thorp JG Gamazon ER Derks EM An analysis of genetically regulated gene expression and the role of co-expression networks across 16 psychiatric and substance use phenotypes Eur J Hum Genet 2022 30 560 566 10.1038/s41431-022-01037-6 35217801 PMC9090912 · DOI
  48. [59]Sadeghi I Gispert JD Palumbo E Muñoz-Aguirre M Wucher V D'Argenio V Brain transcriptomic profiling reveals common alterations across neurodegenerative and psychiatric disorders Comput Struct Biotechnol J 2022 20 4549 4561 10.1016/j.csbj.2022.08.037 36090817 PMC9428860 · DOI
  49. [60]Kaufmann T van der Meer D Doan NT Schwarz E Lund MJ Agartz I Common brain disorders are associated with heritable patterns of apparent aging of the brain Nat Neurosci 2019 22 1617 1623 10.1038/s41593-019-0471-7 31551603 PMC6823048 · DOI
  50. [61]Patel Y Shin J Abé C Agartz I Alloza C Alnæs D Virtual Ontogeny of Cortical Growth Preceding Mental Illness Biol Psychiatry 2022 92 299 313 10.1016/j.biopsych.2022.02.959 35489875 PMC11080987 · DOI

Cited by

Sorted by citations

Authors
Bourque, V.-R., Poulain, C., Proulx, C., Moreau, C. A., Joober, R., Forgeot d’Arc, B., Huguet, G., & Jacquemont, S.
Affiliations
  • Centre Hospitalier Universitaire Sainte-Justine (CA)
  • University of Southern California (US)
  • Douglas Mental Health University Institute (CA)
Corresponding author
Jacquemont, Sébastien
ORCID
Venue
Translational Psychiatry
Publisher
Springer Science and Business Media LLC
Published
2024-03-30
Volume
14
Issue
1
Pages
171-171
ISSN
2158-3188 (ISSN-L)
DOI
10.1038/s41398-024-02866-3
PMC
PMC10981737
OpenAlex
W4393336971
Cited by
48
References
10
Citations by year
2026: 26 · 2025: 18 · 2024: 4
FWCI
3.08
Type
journal article
Language
en
Open access
Licence
Locations
  • Translational Psychiatry (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Institutes of Health
  • Canadian Institutes of Health Research
  • National Institute of Mental Health (U01MH119739, U01MH119690, R01MH129858, R37MH085953)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Mental Health Research Topics
Keywords
mental illness, genetic overlap, phenotypic similarity, schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorder, attention deficit hyperactivity disorder, single nucleotide polymorphisms, gene expression, structural connectivity, functional connectivity, first-degree relatives, diagnostic overlap
MeSH terms
Autism Spectrum Disorder, Attention Deficit Disorder with Hyperactivity, Mental Disorders, Bipolar Disorder, Brain, Major Depressive Disorder, Humans, Phenotype, Schizophrenia, Polymorphism, Single Nucleotide

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