Singh, T., Poterba, T., Curtis, D., ..., SCHEMA consortium, ..., Neale B. M., and Daly M. J. (2022). Rare coding variants in ten genes confer substantial risk for schizophrenia. Nature 2022 Apr;604(7906):509-516. https://doi.org/10.1038/s41586-022-04556-w
Researchers identify new genetic link to schizophrenia
Researchers have found variations in a small number of genes that appear to dramatically increase the likelihood of developing schizophrenia in some people. The interplay of a wide array of other genes is implicated for most people with schizophrenia, a severe brain disorder characterized by hallucinations, delusions and inability to function.
Scientists pinpoint genes that dramatically increase risk of schizophrenia - The Boston Globe
The second study identifies hundreds of common genetic variants that individually contribute only a tiny degree to schizophrenia, but together point to faulty communications between brain cells as a major cause of the disorder.
Landmark study reveals clearest genetic signals yet for schizophrenia risk
In a landmark genetic study of more than 121,000 people, an international consortium called SCHEMA, led by researchers at the Broad Institute of MIT and Harvard, has identified extremely rare protein-disrupting mutations in 10 genes that strongly increase an individual's risk of developing schizophrenia - in one instance, by more than 20-fold.
Singh, T., Walters, J. T. R., Johnstone, M., Curtis, D., Suvisaari, J., Torniainen, M., Rees, E., ..., INTERVAL Study, UK10K Consortium, Palotie, A., Sullivan, P. F., O’Donovan, M. C., Owen M. J., Barrett, J. C. (2017). The contribution of rare variants to risk of schizophrenia in individuals with and without intellectual disability. Nature Genetics, 49:11671173.
Genetic analysis finds rare, damaging variants contribute to the risk of schizophrenia
(Medical Xpress)-Via genetic analysis, a large international team of researchers has found rare, damaging gene variants that they believe contribute to the risk of a person developing schizophrenia. In their paper published in the journal Nature Genetics, the researchers describe their study, which involved analyzing data from a wide variety of sources, comparing what they found and describing their findings.
Singh, T., Kurki, M. I., Curtis, D., Purcell, S. M., Crooks, L., McRae, J., Suvisaari, J., Chheda, H., ..., Swedish Schizophrenia Study, INTERVAL Study, DDD Study, UK10K Consortium, Sullivan, P. F., Hurles, M. E., O’Donovan, M. C., Palotie, A., Owen, M. J., Barrett, J. C. (2016). Rare loss- of-function variants in SETD1A are associated with schizophrenia and developmental disorders. Nature Neuroscience, 19:571-577.
Nature Neuroscience - Volume 19 Issue 4, April 2016
In this Perspective, Murray Sherman discusses connectivity in the thalamocortical system, including the evidence that cortical areas are connected in parallel by direct and transthalamic pathways. Because thalamus receives inputs that form collaterals with subcortical motor regions, the author suggests that it may relay efference copy information.
Rare single gene mutation increases risk of schizophrenia 35-fold, new study suggests
Genetic factors play a major role in schizophrenia but scientists are only now beginning to identify the specific genes involved. A new study published in Nature Neuroscience shows that rare mutations in the SETD1A gene dramatically increase the risk of developing schizophrenia.
Howrigan, D., Rose, S. A., Samocha, K. E., ..., Singh, T., ..., McCarroll, S., Tsuang, M., Neale, B. Exome sequencing in schizophrenia-affected parentoffspring trios reveals risk conferred by protein- coding de novo mutations. Nature Neuroscience 23 (2), 185-193 (2020).
Feng, Y.-C. A., Howrigan, D. P., Abbott, L. E., Tashman, K., Cerrato, F., Singh, T., ..., Neale, B. M. Ultra-Rare Genetic Variation in the Epilepsies: A Whole-Exome Sequencing Study of 17,606 Individuals. (2019). Am. J. Hum. Genet. 105, 267282.
Kyle Satterstrom, F., Walters, R. K., Singh, T., ..., Daly, M. J. Autism spectrum disorder and attention deficit hyperactivity disorder have a similar burden of rare protein-truncating variants. (2019). Nature Neuroscience 22 (12), 1961-1965.
Gardner, E. J., Prigmore, E., Gallone, G., Danecek, P., Samocha, K. E., Handsaker, J., Gerety, S. S., ..., Singh, T., ,..., FitzPatrick, D. R., Firth, H. V., Hurles, M. E. Contribution of retrotransposition to developmental disorders. (2019). Nature Communications 10 (1), 1-10.
Heyne, H. O., Singh, T., Stamberger, H., Abou Jamra, R., Caglayan, H., ..., Lemke, J. R. (2018). De novo Variants In Neurodevelopmental Disorders With Epilepsy. Nature Genetics, 50, 1048-1053 (2018).
Artomov, M., Stratigos, A. J., Kim, I., ..., Singh, T., Barrett, J. C., Adams, D. J., Jonsson, G., Daly, M. J., Tsao, H. (2017). Rare Variant, Gene-Based Association Study of Hereditary Melanoma Using Whole-Exome Sequencing. Journal of the National Cancer Institute, 109 (12): djx083.
McRae, J. F., Clayton, S., Fitzgerald, T. W., Kaplanis, J., Prigmore, E., Rajan, D., Sifrim, A., Aitken, S., Akawi, N., Alvi, M., Ambridge, K., Barrett, D. M., Bayzetinova, T., Jones, P., Jones, W. D., King, D., Krishnappa, N., Mason, L. E., Singh, T., ..., FitzPatrick, D. R., Barrett, J. C., Hurles, M. E. (2017). Prevalence and architecture of de novo mutations in developmental disorders. Nature, 542:433-438.
Sifrim, A., Hitz, M-P., Wilsdon, A., Breckpot, J., Al-Turki, S. H., Thienpont, B., McRae, J., Fitzgerald, T. W., Singh, T., ..., Brook, D. J., and Hurles, M. E. (2016). Distinct genetic archi- tectures for syndromic and nonsyndromic congenital heart defects identified by exome sequencing. Nature Genetics, 9:1060-1065
Mtatiro, S. N., Mgaya, J., Singh, T., Mariki, H., Rooks, H., Soka, D., Mmbando, B., Thein, S. L., Barrett, J. C., Makani, J., Cox, S. E., and Menzel, S. (2015). Genetic association of fetal- hemoglobin levels in individuals with sickle cell disease in Tanzania maps to conserved regulatory elements within the MYB core enhancer. BMC medical genetics, 16(1):4
Singh, T.*, Levine, A. P.*, Smith, P. J., Smith, A. M., Segal, A. W., and Barrett, J. C. (2015). Characterization of expression quantitative trait loci in the human colon. Inflammatory bowel diseases, 21(2):251?6
De Rubeis, S., He, X., Goldberg, A. P., Poultney, C. S., Samocha, K., Cicek, A. E., Kou, Y., Liu, L., Fromer, M., Walker, S., Singh, T., ..., Palotie, A., Schellenberg, G. D., Sklar, P., State, M. W., Sutcliffe, J. S., Walsh, C. A., Scherer, S. W., Zwick, M. E., Barrett, J. C., Cutler, D. J., Roeder, K., Devlin, B., Daly, M. J., and Buxbaum, J. D. (2014). Synaptic, transcriptional and chromatin genes disrupted in autism. Nature, 515(7526):209?15
Mtatiro, S. N.*, Singh, T.*, Rooks, H., Mgaya, J., Mariki, H., Soka, D., Mmbando, B., Msaki, E., Kolder, I., Thein, S. L., Menzel, S., Cox, S. E., Makani, J., and Barrett, J. C. (2014). Genome wide association study of fetal hemoglobin in sickle cell anemia in Tanzania. PloS one, 9(11):e111464
Gao, T., McKenna, B., Li, C., Reichert, M., Nguyen, J., Singh, T., Yang, C., Pannikar, A., Doliba, N., Zhang, T., Stoffers, D. A., Edlund, H., Matschinsky, F., Stein, R., and Stanger, B. Z. (2014). Pdx1 maintains β cell identity and function by repressing an α cell program. Cell metabolism, 19(2):259?71
Gao, T., Zhou, D., Yang, C., Singh, T., Penzo-Mendez, A., Maddipati, R., Tzatsos, A., Bardeesy, N., Avruch, J., and Stanger, B. Z. (2013). Hippo signaling regulates differentiation and maintenance in the exocrine pancreas. Gastroenterology, 144(7):1543?53, 1553.e1