What psychiatric genetics has taught us about the nature of psychiatric illness and what is left to learn
Abstract
Psychiatric genetics has taught us a great deal about the nature of psychiatric disorders. Traditional family, twin and adoption studies have demonstrated the substantial role of genetic factors in their etiology, clarified the role of genetic factors in comorbidity, elucidated development pathways, and documented the importance of gene-environment correlation and interaction. We have also received some hard lessons when we were unable to detect replicable genes of large effect size and found that our much-valued candidate genes did not live up to their expected promise. With more mature molecular and statistical methods, we are entering now a different era. Statistical analyses of aggregate molecular signals are validating earlier heritability estimates. Replicated findings from genome-wide association studies are beginning to emerge, as are discoveries of large-effect size rare genomic variants. The number of such findings is likely to soon grow dramatically. The most pressing question facing the field is what biological picture these results will reveal. I articulate four possible scenarios that reflect (i) no, (ii) minimal, (iii) moderate and (iv) high biological coherence in the replicated molecular variant findings, which are soon likely to emerge. I discuss the factors that will likely influence these patterns, including the problems of etiological heterogeneity and multiple realizability. These findings could provide critical insights into the underlying biology of ou…
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No specific causal genetic variants for antisocial behaviour have been identified.
“Specific causal genetic variants have, however, not been identified.”
From Genome-Wide Association Studies of a Broad Spectrum of Antisocial Behavior (2017) · cites this paper as Kendler, 2013
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
Systematic Localization of Common Disease-Associated Variation in Regulatory DNA
Maurano, M. T., Humbert, R., Rynes, E., Thurman, R. E., Haugen, E., Wang, H., Reynolds, A. P., Sandstrom, R., Qu, H., Brody, J., et al. (2012) · Science · doi:10.1126/science.1222794 · Cited by 3,716 · see citing works
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
Gene Ontology Analysis of GWA Study Data Sets Provides Insights into the Biology of Bipolar Disorder
Holmans, P., Green, E. K., Pahwa, J. S., Ferreira, M. A. R., Purcell, S. M., Sklar, P., Owen, M. J., O'Donovan, M. C., & Craddock, N. (2009) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2009.05.011 · Cited by 378 · see citing works
Diverse Genome-wide Association Studies Associate the IL12/IL23 Pathway with Crohn Disease
Wang, K., Zhang, H., Kugathasan, S., Annese, V., Bradfield, J. P., Russell, R. K., Sleiman, P. M. A., Imielinski, M., Glessner, J., Hou, C., et al. (2009) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2009.01.026 · Cited by 291 · see citing works
O'Dushlaine, C., Kenny, E., Heron, E., Donohoe, G., Gill, M., Morris, D., The International Schizophrenia Consortium, & Corvin, A. (2011) · Molecular Psychiatry · doi:10.1038/mp.2010.7 · Cited by 228 · see citing works
The Emerging Biology of Autism Spectrum Disorders
State, M. W., & Šestan, N. (2012) · Science · doi:10.1126/science.1224989 · Cited by 164 · see citing works
Kendler, K. S., & Myers, J. (2009) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2009.09020182 · Cited by 62 · see citing works
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The Lancet Commission on global mental health and sustainable development
Patel, V., Saxena, S., Lund, C., Thornicroft, G., Baingana, F., Bolton, P., Chisholm, D., Collins, P. Y., Cooper, J. L., Eaton, J., et al. (2018) · The Lancet · doi:10.1016/s0140-6736(18)31612-x · Cited by 3,692 · see citing works
Häuser, W., Ablin, J., Fitzcharles, M.-A., Littlejohn, G., Luciano, J. V., Usui, C., & Walitt, B. (2015) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2015.22 · Cited by 505 · see citing works
Hankin, B. L., Young, J. F., Abela, J. R. Z., Smolen, A., Jenness, J. L., Gulley, L. D., Technow, J. R., Gottlieb, A. B., Cohen, J. R., & Oppenheimer, C. W. (2015) · Journal of Abnormal Psychology · doi:10.1037/abn0000089 · Cited by 443 · see citing works
The road to precision psychiatry: translating genetics into disease mechanisms
Gandal, M. J., Leppa, V., Won, H., Parikshak, N. N., & Geschwind, D. H. (2016) · Nature Neuroscience · doi:10.1038/nn.4409 · Cited by 223 · see citing works
Genome-Wide Association Studies of a Broad Spectrum of Antisocial Behavior
Tielbeek, J. J., Johansson, A., Polderman, T. J. C., Rautiainen, M.-R., Jansen, P., Taylor, M., Tong, X., Lu, Q., Burt, A. S., Tiemeier, H., et al. (2017) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2017.3069 · Cited by 194 · see citing works
“The lack of replicationof candidate genes forASB is consistentwithother candidate gene findings inpsychiatry,which for themost part have failed to identify reproducible and clinically useful genetic variants.(13) This is attributable in part to the a priori inferences of the classic candidate gene approach, which incr…”
BackgroundArloth, J., Bogdan, R., Weber, P., Frishman, G., Menke, A., Wagner, K. V., Balsevich, G., Schmidt, M. V., Karbalai, N., Czamara, D., et al. (2015) · Neuron · doi:10.1016/j.neuron.2015.05.034 · Cited by 142 · see citing works
Neuropeptide and small transmitter coexistence: Fundamental studies and relevance to mental illness
Hökfelt, T., Barde, S., Xu, Z.-Q. D., Kuteeva, E., Rüegg, J., Le Maitre, E., Risling, M., Kehr, J., Ihnatko, R., Theodorsson, E., et al. (2018) · Frontiers in Neural Circuits · doi:10.3389/fncir.2018.00106 · Cited by 139 · see citing works
A quantitative approach to neuropsychiatry: The why and the how
Kas, M. J., Penninx, B., Sommer, B., Serretti, A., Arango, C., & Marston, H. (2019) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.12.008 · Cited by 112 · see citing works
Pinto, J. V., Moulin, T. C., & Amaral, O. B. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.10.001 · Cited by 103 · see citing works
Goossens, L., van Roekel, E., Verhagen, M., Cacioppo, J. T., Cacioppo, S., Maes, M., & Boomsma, D. I. (2015) · Perspectives on Psychological Science · doi:10.1177/1745691614564878 · Cited by 103 · see citing works
An overview of the neurobiology of suicidal behaviors as one meta-system
Sokolowski, M., Wasserman, J., & Wasserman, D. (2015) · Molecular Psychiatry · doi:10.1038/mp.2014.101 · Cited by 50 · see citing works
Early adversity as the prototype gene × environment interaction in mental disorders?
Martins, J., Yusupov, N., Binder, E. B., Brückl, T. M., & Czamara, D. (2022) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2022.173371 · Cited by 22 · see citing works
Ruisch, I. H., Dietrich, A., Glennon, J. C., Buitelaar, J. K., & Hoekstra, P. J. (2019) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-018-0964-5 · Cited by 19 · see citing works
- Authors
- Kendler, K. S.
- Affiliations
- Virginia Commonwealth University (US)
- Corresponding author
- Kendler, Kenneth S
- ORCID
- Kendler, Kenneth S
- Venue
- Molecular Psychiatry
- Published
- 2013-04-30
- Volume
- 18
- Issue
- 10
- Pages
- 1058-1066
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- OpenAlex
- W2018332195
- Cited by
- 178
- References
- 8
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 5 · 2023: 7 · 2022: 13 · 2021: 13 · 2020: 6 · 2019: 12 · 2018: 11 · 2017: 49 · 2016: 13 · 2015: 22 · 2014: 14 · 2013: 4 · 2012: 2
- FWCI
- 2.14
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Keywords
- psychiatric genetics, heritability, genetic comorbidity, gene-environment interaction, candidate genes, genome-wide association study, etiologic heterogeneity, multiple realizability, biological coherence, mind-brain relationship, mental illness
- MeSH terms
- Adoption, Mental Disorders, Genetics, Behavioral, Humans, Models, Genetic, Models, Neurological, Models, Psychological, Research Design, Risk, Schizophrenia, Causality, Case-Control Studies, Twin Studies as Topic, Genetic Heterogeneity, Quantitative Trait, Heritable, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Genetic Association Studies, Gene-Environment Interaction
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