Genomic Analysis of Mental Illness: A Changing Landscape
Abstract
THE EARTH IS SHIFTING BENEATH PSYCHIATRIC GENETics. Schizophrenia and other complex neuropsychiatric disorders are characterized by genetic heterogeneity to an extent far greater than previously recognized. Individually rare mutations, many de novo and others a few generations old, may be collectively responsible for a substantial portion of mental illness. The degree of heterogeneity is so great that most unrelated patients may have a different genetic cause. This phenomenon has fundamental implications for translational and interventional research.
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There have been multiple meta-analysis consortia in psychiatric genetics, of which the Psychiatric Genomics Consortium is the largest and most encompassing.
“there have been multiple meta-analysis 146,147 consortia in psychiatric genetics, of which the Psychiatric Genomics Consortium (http://pgc.unc.edu) is the largest and most encompassing. 123,148,149”
From Genetic architectures of psychiatric disorders: the emerging picture and its implications (2012) · cites this paper as [123]
Cites
Common polygenic variation contributes to risk of schizophrenia and bipolar disorder
The International Schizophrenia Consortium (2009) · Nature · doi:10.1038/nature08185 · Cited by 4,821 · see citing works
Rare Structural Variants Disrupt Multiple Genes in Neurodevelopmental Pathways in Schizophrenia
Walsh, T., McClellan, J. M., McCarthy, S. E., Addington, A. M., Pierce, S. B., Cooper, G. M., Nord, A. S., Kusenda, M., Malhotra, D., Bhandari, A., et al. (2008) · Science · doi:10.1126/science.1155174 · Cited by 1,800 · see citing works
Self-citationLarge recurrent microdeletions associated with schizophrenia.
GROUP, Stefansson, H., Rujescu, D., Cichon, S., Pietiläinen, O. P. H., Ingason, A., Steinberg, S., Fossdal, R., Sigurdsson, E., Sigmundsson, T., et al. (2008) · Nature · doi:10.1038/nature07229 · Cited by 1,745 · see citing works
Common variants conferring risk of schizophrenia
†Genetic Risk and Outcome in Psychosis (GROUP), Stefansson, H., Ophoff, R. A., Steinberg, S., Andreassen, O. A., Cichon, S., Rujescu, D., Werge, T., Pietiläinen, O. P. H., Mors, O., et al. (2009) · Nature · doi:10.1038/nature08186 · Cited by 1,677 · see citing works
Rare chromosomal deletions and duplications increase risk of schizophrenia
The International Schizophrenia Consortium (2008) · Nature · doi:10.1038/nature07239 · Cited by 1,475 · see citing works
Common variants on chromosome 6p22.1 are associated with schizophrenia
Shi, J., Levinson, D. F., Duan, J., Sanders, A. R., Zheng, Y., Pe’er, I., Dudbridge, F., Holmans, P., Whittemore, A. S., Mowry, B. J., et al. (2009) · Nature · doi:10.1038/nature08192 · Cited by 1,154 · see citing works
Identification of loci associated with schizophrenia by genome-wide association and follow-up
Molecular Genetics of Schizophrenia Collaboration, O'Donovan, M. C., Craddock, N., Norton, N., Williams, H., Peirce, T., Moskvina, V., Nikolov, I., Hamshere, M., Carroll, L., et al. (2008) · Nature Genetics · doi:10.1038/ng.201 · Cited by 1,070 · see citing works
Genetic Heterogeneity in Human Disease
McClellan, J., & King, M.-C. (2010) · Cell · doi:10.1016/j.cell.2010.03.032 · Cited by 981 · see citing works
Self-citationStrong association of de novo copy number mutations with sporadic schizophrenia
Xu, B., Roos, J. L., Levy, S., van Rensburg, E. J., Gogos, J. A., & Karayiorgou, M. (2008) · Nature Genetics · doi:10.1038/ng.162 · Cited by 813 · see citing works
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Genetic architectures of psychiatric disorders: the emerging picture and its implications
Sullivan, P. F., Daly, M. J., & O'Donovan, M. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3240 · Cited by 1,177 · see citing works
De novo mutations in human genetic disease
Veltman, J. A., & Brunner, H. G. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3241 · Cited by 845 · see citing works
Estimating the proportion of variation in susceptibility to schizophrenia captured by common SNPs
The Schizophrenia Psychiatric Genome-Wide Association Study Consortium (PGC-SCZ), Lee, S. H., The International Schizophrenia Consortium (ISC), The Molecular Genetics of Schizophrenia Collaboration (MGS), DeCandia, T. R., Ripke, S., Yang, J., Sullivan, P. F., Goddard, M. E., Keller, M. C., et al. (2012) · Nature Genetics · doi:10.1038/ng.1108 · Cited by 579 · see citing works
Lee, S. H., Harold, D., Nyholt, D. R., ANZGene Consortium, International Endogene Consortium, the Genetic and Environmental Risk for Alzheimer's disease (GERAD1) Consortium, Goddard, M. E., Zondervan, K. T., Williams, J., Montgomery, G. W., et al. (2013) · Human Molecular Genetics · doi:10.1093/hmg/dds491 · Cited by 217 · see citing works
A Genome-Wide Association Study of Depressive Symptoms
Hek, K., Demirkan, A., Lahti, J., Terracciano, A., Teumer, A., Cornelis, M. C., Amin, N., Bakshis, E., Baumert, J., Ding, J., et al. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.09.033 · Cited by 172 · see citing works
Luo, R., Sanders, S. J., Tian, Y., Voineagu, I., Huang, N., Chu, S. H., Klei, L., Cai, C., Ou, J., Lowe, J. K., et al. (2012) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2012.05.011 · Cited by 167 · see citing works
A Comprehensive Family-Based Replication Study of Schizophrenia Genes
Åberg, K. A., Liu, Y., Bukszár, J., McClay, J. L., Khachane, A. N., Andreassen, O. A., Blackwood, D., Corvin, A. P., Djurovic, S., Gurling, H., et al. (2013) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2013.288 · Cited by 150 · see citing works
High Loading of Polygenic Risk for ADHD in Children With Comorbid Aggression
Hamshere, M. L., Langley, K., Martin, J., Agha, S. S., Stergiakouli, E., Anney, R. J. L., Buitelaar, J., Faraone, S. V., Lesch, K.-P., Neale, B. M., et al. (2013) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2013.12081129 · Cited by 144 · see citing works
Genome-wide Association Studies: Findings at the Major Histocompatibility Complex Locus in Psychosis
Corvin, A. P., & Morris, D. W. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.09.018 · Cited by 135 · see citing works
Schizophrenia: susceptibility genes, dendritic-spine pathology and gray matter loss
Bennett, M. R. (2011) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2011.08.003 · Cited by 126 · see citing works
What is complex about complex disorders?
Mitchell, K. J. (2012) · Genome biology · doi:10.1186/gb-2012-13-1-237 · Cited by 115 · see citing works
The Genetic Architecture of Schizophrenia: New Mutations and Emerging Paradigms
Rodriguez‐Murillo, L., Gogos, J. A., & Karayiorgou, M. (2011) · Annual Review of Medicine · doi:10.1146/annurev-med-072010-091100 · Cited by 120 · see citing works
Strategic Approaches to Unraveling Genetic Causes of Cardiovascular Diseases
Marian, A. J., & Belmont, J. W. (2011) · Circulation Research · doi:10.1161/circresaha.110.236067 · Cited by 107 · see citing works
The genomics of schizophrenia: update and implications
Giusti‐Rodríguez, P., & Sullivan, P. F. (2013) · Journal of Clinical Investigation · doi:10.1172/jci66031 · Cited by 95 · see citing works
Srivastava, D. P., Woolfrey, K. M., Jones, K. A., Anderson, C. T., Smith, K. R., Russell, T. A., Lee, H., Yasvoina, M. V., Wokosin, D. L., Özdi̇nler, P. H., et al. (2012) · PLoS Biology · doi:10.1371/journal.pbio.1001350 · Cited by 85 · see citing works
Psychiatric Genomics and Mental Health Treatment: Setting the Ethical Agenda
Kong, C., Dunn, M., & Parker, M. J. (2017) · The American Journal of Bioethics · doi:10.1080/15265161.2017.1284915 · Cited by 71 · see citing works
Blanco‐Gómez, A., Castillo‐Lluva, S., Sáez‐Freire, M. D. M., Hontecillas‐Prieto, L., Mao, J., Castellanos‐Martín, A., & Pérez‐Losada, J. (2016) · BioEssays · doi:10.1002/bies.201600084 · Cited by 68 · see citing works
Elements of ‘missing heritability’
Marian, A. J. (2012) · Current Opinion in Cardiology · doi:10.1097/hco.0b013e328352707d · Cited by 67 · see citing works
Transcription factor 4 (TCF4) and schizophrenia: integrating the animal and the human perspective
Quednow, B. B., Brzózka, M. M., & Rossner, M. J. (2014) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-013-1553-4 · Cited by 66 · see citing works
Case Formulation After Engel—The 4P Model: A Philosophical Case Conference
Bolton, J. W. (2014) · Philosophy, psychiatry & psychology · doi:10.1353/ppp.2014.0027 · Cited by 63 · see citing works
Walters, J., Rujescu, D., Franke, B., Giegling, I., Vásquez, A. A., Hargreaves, A., Russo, G., Morris, D. W., Hoogman, M., Costa, A. D., et al. (2013) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2013.12020226 · Cited by 62 · see citing works
Rediscovering the value of families for psychiatric genetics research
Glahn, D. C., Nimgaonkar, V. L., Raventós, H., Rojas, J. C., McIntosh, A. M., Thomson, P. A., Jablensky, A. V., McCarthy, N. S., Charlesworth, J., Blackburn, N. B., et al. (2018) · Molecular Psychiatry · doi:10.1038/s41380-018-0073-x · Cited by 58 · see citing works
Schizophrenia genomics: genetic complexity and functional insights
Sullivan, P. F., Yao, S., & Hjerling‐Leffler, J. (2024) · Nature reviews. Neuroscience · doi:10.1038/s41583-024-00837-7 · Cited by 62 · see citing works
Synapsin III: Role in neuronal plasticity and disease
Porton, B., Wetsel, W. C., & Kao, H. (2011) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2011.07.007 · Cited by 58 · see citing works
Liao, H.-M., Chao, Y.-L., Huang, A.-L., Cheng, M.-C., Chen, Y.-J., Lee, K.-F., Fang, J., Hsu, C.-H., & Chen, C. (2012) · Schizophrenia Research · doi:10.1016/j.schres.2012.05.015 · Cited by 53 · see citing works
Wu, Y., Liu, X., Luo, H., Deng, W., Zhao, G., Wang, Q., Zhang, L., Ma, X., Liu, X., Murray, R. M., et al. (2012) · Psychiatry Research · doi:10.1016/j.psychres.2012.01.020 · Cited by 52 · see citing works
Li, S. C., Tachiki, L. M. L., Kabeer, M. H., Dethlefs, B. A., Anthony, M. J., & Loudon, W. G. (2014) · Cancer Cell International · doi:10.1186/s12935-014-0115-7 · Cited by 47 · see citing works
Andlauer, T. F. M., Parra, J. G., Streit, F., Strohmaier, J., González, M. J., Flores, S. G., Cabaleiro, F., Noriega, F. D. R., Pérez, F., González, J. H., et al. (2019) · Molecular Psychiatry · doi:10.1038/s41380-019-0558-2 · Cited by 43 · see citing works
Mutations affecting synaptic levels of neurexin-1β in autism and mental retardation
Camacho-Garcia, R. J., Planelles, M. I., Margalef-Català, M., Pecero, M. L., Martínez‐Leal, R., Aguilera, F., Vilella, E., Martı́nez-Mir, A., & Scholl, F. G. (2012) · Neurobiology of Disease · doi:10.1016/j.nbd.2012.03.031 · Cited by 35 · see citing works
VarScan2 analysis of de novo variants in monozygotic twins discordant for schizophrenia
Reble, E., Castellani, C. A., Melka, M. G., O’Reilly, R., & Singh, S. M. (2017) · Psychiatric Genetics · doi:10.1097/ypg.0000000000000162 · Cited by 32 · see citing works
A Systematic Approach to Multifactorial Cardiovascular Disease
Schwartz, S. M., Schwartz, H. T., Horvath, S., Schadt, E., & Lee, S. (2012) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.112.300123 · Cited by 31 · see citing works
A family-based study of common polygenic variation and risk of schizophrenia
Ruderfer, D. M., Kirov, G., Chambert, K., Moran, J. L., Owen, M. J., O'Donovan, M. C., Sklar, P., & Purcell, S. M. (2011) · Molecular Psychiatry · doi:10.1038/mp.2011.34 · Cited by 28 · see citing works
No evidence that common genetic risk variation is shared between schizophrenia and autism
Vorstman, J. A. S., Anney, R., Derks, E. M., Gallagher, L., Gill, M., de Jonge, M. V., van Engeland, H., Kahn, R. S., & Ophoff, R. A. (2012) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32121 · Cited by 25 · see citing works
Identifying bipolar disorder susceptibility loci in a densely affected pedigree
Collins, A. L., Kim, Y., Szatkiewicz, J., Bloom, R. J., Hilliard, C. E., Quackenbush, C. R., Meier, S., Rivas, F., Mayoral, F., Cichon, S., et al. (2012) · Molecular Psychiatry · doi:10.1038/mp.2012.176 · Cited by 24 · see citing works
De novo non-synonymous TBL1XR1 mutation alters Wnt signaling activity
Nishi, A., Numata, S., Tajima, A., Zhu, X., Ito, K., Saito, A., Kato, Y., Kinoshita, M., Shimodera, S., Ono, S., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-02792-z · Cited by 23 · see citing works
Systems psychopharmacology: A network approach to developing novel therapies
Gebicke‐Haerter, P. J. (2016) · World Journal of Psychiatry · doi:10.5498/wjp.v6.i1.66 · Cited by 16 · see citing works
Neural circuitry and precision medicines for mental disorders: are they compatible?
Dean, C. E. (2018) · Psychological Medicine · doi:10.1017/s0033291718003252 · Cited by 16 · see citing works
Genetic testing for autism: recent advances and clinical implications
Miller, D. T. (2010) · Expert Review of Molecular Diagnostics · doi:10.1586/erm.10.82 · Cited by 16 · see citing works
Nickl‐Jockschat, T., Stöcker, T., Krug, A., Markov, V., Huang, R., Schneider, F. W., Habel, U., Eickhoff, S. B., Zerres, K., Nöthen, M. M., et al. (2014) · Brain and Behavior · doi:10.1002/brb3.203 · Cited by 15 · see citing works
Genetics of schizophrenia from a clinicial perspective
Kukshal, P., Thelma, B. K., Nimgaonkar, V. L., & Deshpande, S. N. (2012) · International Review of Psychiatry · doi:10.3109/09540261.2012.709178 · Cited by 14 · see citing works
Hu, T., Wu, C., Hsu, S.-H., Tsai, H.-Y., Cheng, F.-Y., & Cheng, M.-C. (2022) · Journal of Personalized Medicine · doi:10.3390/jpm12050783 · Cited by 13 · see citing works
Dahoun, T., Pardiñas, A. F., Veronese, M., Bloomfield, M., Jauhar, S., Bonoldi, I., Froudist‐Walsh, S., Nosarti, C., Korth, C., Hennah, W., et al. (2018) · Human Molecular Genetics · doi:10.1093/hmg/ddy242 · Cited by 11 · see citing works
Saffen, D. W. (2015) · Science China Life Sciences · doi:10.1007/s11427-012-4336-5 · Cited by 8 · see citing works
How informative is a negative finding in a small pharmacogenetic study?
Bacanu, S., Whittaker, J. C., & Nelson, M. R. (2011) · The Pharmacogenomics Journal · doi:10.1038/tpj.2011.58 · Cited by 8 · see citing works
Psychiatric Molecular Genetics and the Ethics of Social Promises
Sadler, J. Z. (2010) · Journal of Bioethical Inquiry · doi:10.1007/s11673-010-9273-z · Cited by 7 · see citing works
Andlauer, T. F. M., Parra, J. G., Streit, F., Strohmaier, J., González, M. J., Flores, S. G., Cabaleiro, F., Noriega, F. D. R., Pérez, F., González, J. H., et al. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/468975 · Cited by 7 · see citing works
Clinically Relevant Phenomenology: The Nature of Psychosis
McClellan, J. (2011) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2011.04.010 · Cited by 6 · see citing works
Self-citationLoe-Mie, Y., Plançon, C., Dubertret, C., Yoshikawa, T., Yalcin, B., Collins, S. C., Boland, A., Deleuze, J., Gorwood, P. A. P. M., Benmessaoud, D., et al. (2024) · Life · doi:10.3390/life14020244 · Cited by 5 · see citing works
Grand Challenges in Psychosomatic Research
Jindal, R. D., & Jennings, J. R. (2010) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2010.00131 · Cited by 4 · see citing works
Caplan, R. (2016) · Wiley eBooks · doi:10.1002/9781119125556.devpsy321 · Cited by 3 · see citing works
The future of psychiatric research
Caldieraro, M. A. (2016) · Trends in Psychiatry and Psychotherapy · doi:10.1590/2237-6089-2016-0046 · Cited by 2 · see citing works
A Two-State Epistasis Model Reduces Missing Heritability of Complex TraitsPreprint
Bubb, K. L., & Queitsch, C. (2015) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/017491 · Cited by 2 · see citing works
Causation and the Limits of Modern Genetics
Berman, J. J. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-419988-0.00009-2 · Cited by 1 · see citing works
Anxiety Disorders and Depression in Older Adults
Hek, K. (2013) · RePub (Erasmus University Rotterdam) · Cited by 1 · see citing works
Dej, E. (2016) · uO Research (University of Ottawa) · doi:10.20381/ruor-4930 · Cited by 1 · see citing works
Investigation of Gene Splicing Variants Contributing Risk to Psychiatric Disorders
Reble, E. (2017) · TSpace (University of Toronto) · Cited by 1 · see citing works
Cachaza, N. C. C. (2012) · Tesis Doctorals en Xarxa (Consorci de Serveis Universitaris de Catalunya)
Rare Diseases and Common Diseases: Understanding their Relationships
Berman, J. J. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-419988-0.00012-2
NEXT GENERATION SEQUENCING DATA IN BOVINE: QUALITY CONTROL, IMPUTATION, AND APPLICATION
Larmer, S. G. (2016) · The Atrium (University of Guelph)
Gene coexpression network and machine learning in personalized psychiatry
Ciobanu, L. G., Cearns, M., & Baune, B. T. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-813176-3.00031-6
Ryan, N., Ormond, C., Brady, P., Heron, E. A., & Corvin, A. P. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-819602-1.00002-4
Tyrer, P. J. (2013) · The British Journal of Psychiatry · doi:10.1192/bjp.202.1.80
- Authors
- McClellan, J., & King, M.-C.
- Affiliations
- University of Washington (US)
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2010-06-23
- Volume
- 303
- Issue
- 24
- Pages
- 2523
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- OpenAlex
- W2064214582
- Cited by
- 63
- References
- 9
- Citations by year
- 2024: 2 · 2022: 2 · 2019: 2 · 2018: 4 · 2017: 4 · 2016: 6 · 2015: 2 · 2014: 7 · 2013: 8 · 2012: 16
- FWCI
- 7.42
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Keywords
- schizophrenia, psychiatric genetics, genetic heterogeneity, de novo mutations, rare mutations, neuropsychiatric disorders, mental illness, genetic causes of disease
- MeSH terms
- Alleles, Autistic Disorder, Mental Disorders, Humans, Mutation, Risk, Schizophrenia, Genetic Heterogeneity
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