Singh Lab - Statistical Genomics of Psychiatric Disorders
Location and Contact Information
Principal Investigator
For more updated information and contact information, please visit tjsinghlab.com.
We are a collaborative and interdisciplinary research team at The Department of Psychiatry at Columbia University Irving Medical Center and the New York State Psychiatric Institute, and affiliated with Mortimer B. Zuckerman Mind Brain Behavior Institute at Columbia University and the New York Genome Center.
Mental, behavioral, and emotional disorders, which include schizophrenia, anxiety, depression, and bipolar disorders, are highly debilitating and diminish a person’s ability to function and quality of life. Unfortunately, few novel and effective therapies have developed in recent decades, hampered by our limited understanding of disease mechanisms.
We are interested in using genomics to answer specific questions related to the causes of mental illnesses. For instance, which genes are associated with an increased risk of schizophrenia or major depression? What biological pathways and processes are these genes involved in? Which cell types and neuronal circuits are perturbed by the risk variants and genes linked to each psychiatric disorder?
In the last decade, large global efforts have generated genetic data for hundreds of thousands of individuals. These large data sets were initially designed to study specific traits and conditions. As part of these collaborations, we have identified specific genes associated with severe psychiatric disorders. More recently, genetic data from national biobanks allow us to explore thousands of phenotypes in hundreds of thousands of individuals. We will use the depth and diversity of these datasets to study and characterize the effects of genetic risk factors for psychiatric and neurodevelopmental disorders.
To this end, our team generates, analyzes, and integrates genetic and functional data to understand the causes of mental illnesses. We will use these findings to build specific biological hypotheses on disease pathogenesis that lead to new therapies. Broadly, we: (i) develop and apply methods to identify robust genetic associations and pinpoint disease-specific genes through the meta-analyses of sequence data of psychiatric disorders, (ii) characterize the range of clinical outcomes of common and rare genetic risk by studying clinical collections and population biobanks, and (iii) develop methods and approaches to integrate genetic and functional data to prioritize biological tissues, cell types, and processes relevant to disease.
Biography
Tarjinder Singh, Ph.D., is an Assistant Professor in Computational and Statistical Genomics at the Columbia University Department of Psychiatry, with joint appointments at the Mortimer B. Zuckerman Mind Brain Behavior Institute and the New York State Psychiatric Institute. He is also an Associate Member at the New York Genome Center.
His team focuses on generating, analyzing, and integrating genetic and functional data to understand the causes of mental illnesses. As part of global collaborative efforts, he has identified specific genes associated with severe psychiatric disorders. With statistical genetics as a foundation, his team develops new approaches to analyze sequence data from hundreds of thousands of individuals. Using results from genetic and functional, his team hopes to build specific biological hypotheses on disease pathogenesis that lead to more effective therapeutic development.
He joined the NYGC from the Analytical and Translational Unit of the Massachusetts General Hospital and the Stanley Center for Psychiatric Research at the Broad Institute of Harvard and M.I.T. There, he worked as a post-doctoral fellow (2017 - 2020) and as an Instructor at Harvard Medical School (2020 - 2022) with Dr. Mark Daly and Dr. Benjamin Neale. He obtained his Ph.D. in Biological Sciences from the University of Cambridge, England, and the Wellcome Trust Sanger Institute working with Dr. Jeffrey Barrett in 2016. He received his Bachelor’s Degree in Biology, Mathematics, and Economics at Williams College in 2012.
Select Publications
For a full list of publications, please visit Google Scholar at https://scholar.google.com/citations?hl=en&user=EykSN3wAAAAJ&view_op=list_works&sortby=pubdate
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
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.
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.
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