The DOI matches its Crossref record; 72 of the 72 references it cites were found in a registry or an index.
Genetic architecture of 11 major psychiatric disorders at biobehavioral, functional genomic and molecular genetic levels of analysis
Open accessAbstract
Abstract We systematically interrogate the joint genetic architecture of 11 major psychiatric disorders at biobehavioral, functional genomic, and molecular genetic levels of analysis. We identify four broad factors (Neurodevelopmental, Compulsive, Psychotic, and Internalizing) that underlie genetic correlations among the disorders, and test whether these factors adequately explain their genetic correlations with biobehavioral traits. We introduce Stratified Genomic Structural Equation Modelling, which we use to identify gene sets and genomic regions that disproportionately contribute to pleiotropy, including protein-truncating variant intolerant genes expressed in excitatory and GABAergic brain cells that are enriched for pleiotropy between disorders with psychotic features. Multivariate association analyses detect a total of 152 (20 novel) independent loci which act on the four factors, and identify nine loci that act heterogeneously across disorders within a factor. Despite moderate to high genetic correlations across all 11 disorders, we find very little utility of, or evidence for, a single dimension of genetic risk across psychiatric disorders.
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Cited by
Hatoum, A. S., Colbert, S. M. C., Johnson, E. C., Huggett, S. B., Deak, J. D., Pathak, G. A., Jennings, M. V., Paul, S. E., Karcher, N. R., Hansen, I., et al. (2023) · Nature Mental Health · doi:10.1038/s44220-023-00034-y · Cited by 241
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Garcia-Argibay, M., Brikell, I., Thapar, A., Lichtenstein, P., Lundström, S., Demontis, D., & Larsson, H. (2024) · Biological Psychiatry · doi:10.1016/j.biopsych.2023.07.017 · Cited by 33
Tesli, N., Jaholkowski, P., Haukvik, U. K., Jangmo, A., Haram, M., Rokicki, J., Friestad, C., Tielbeek, J. J., Næss, Ø., Skardhamar, T., et al. (2024) · Psychiatry Research · doi:10.1016/j.psychres.2023.115628 · Cited by 14
Veltman, L. J., Lee, S. H., Benyamin, B., 23andMe Research Institute, Cohen-Woods, S., Hyppönen, E., & Stacey, D. (2026) · Psychological Medicine · doi:10.1017/s0033291726106308
Metadata
- Authors
- Grotzinger, A. D., Mallard, T. T., Akingbuwa, W. A., Ip, H. F., Adams, M. J., Lewis, C. M., McIntosh, A. M., Grove, J., Dalsgaard, S., Lesch, K.-P., Strom, N., Meier, S. M., Mattheisen, M., Børglum, A. D., Mors, O., Breen, G., iPSYCH, Mattheisen, M., Mors, O., Tourette Syndrome and Obsessive Compulsive Disorder Working Group of the Psychiatric Genetics Consortium, Bipolar Disorder Working Group of the Psychiatric Genetics Consortium, Major Depressive Disorder Working Group of the Psychiatric Genetics Consortium, Schizophrenia Working Group of the Psychiatric Genetics Consortium, Meier, S. M., Lee, P. H., Kendler, K. S., Smoller, J. W., Tucker-Drob, E. M., & Nivard, M. G.
- Venue
- Nature Genetics
- Published
- 2022-05
- Volume
- 54
- Issue
- 5
- Pages
- 548-559
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W4229010457
- Cited by
- 328
- References
- 72
- FWCI
- 33.79
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Grotzinger, A. D., Mallard, T. T., Akingbuwa, W. A., Ip, H. F., Adams, M. J., Lewis, C. M., McIntosh, A. M., Grove, J., Dalsgaard, S., Lesch, K.-P., Strom, N., Meier, S. M., Mattheisen, M., Børglum, A. D., Mors, O., Breen, G., iPSYCH, Mattheisen, M., Mors, O., . . . Nivard, M. G. (2022). Genetic architecture of 11 major psychiatric disorders at biobehavioral, functional genomic and molecular genetic levels of analysis. Nature Genetics. https://doi.org/10.1038/s41588-022-01057-4
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