Publications

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Kun, E., Javan, E. M., Smith, O., Gulamali, F., de la Fuente, J., Flynn, B. I., Vajrala, K., Trutner, Z., Jayakumar, P., Tucker-Drob, E. M., Sohail, M., Singh, T.*, & Narasimhan, V. M.* (2023). The genetic architecture and evolution of the human skeletal form. Science, 381(6655), eadf8009. https://doi.org/10.1126/science.adf8009

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Scientists uncover genes that gave humans the ability to walk upright

Researchers also identified the variants associated with arthritis.

www.independent.co.uk

These Bones Were Made for Walking

The genetic changes that made it possible for humans to walk upright have been uncovered in a study that also shows how slight variations in skeletal proportions are linked to arthritis.

www.cuimc.columbia.edu

Short arms and lanky legs: the genetic basis of walking on two legs

Nature - Genome-wide map reveals regions associated with skeletal changes that enabled humans to walk upright.

www.nature.com

Gene shift helped ancient humans to walk upright

Scientists have identified the genetic changes that enabled our ancient ancestors to stop dragging their knuckles and start walking upright on two legs about s

www.thetimes.co.uk

AI and the Evolution of the Human Skeletal Form - New York Genome Center

Deep learning sheds new light on musculoskeletal diseases and genomic evidence related to the evolution of the human skeletal form NEW YORK, NY (July 20, 2023) – Researchers have used artificial intelligence and X-ray images to study the genetic basis, evolution, and health consequences of human skeletal traits, according to a new study in Science.

www.nygenome.org

These bones were made for walking: Study uncovers genetic changes that made bipedalism possible

Perhaps the most profound advance in primate evolution occurred about 6 million years ago when our ancestors started walking on two legs. The gradual shift to bipedal locomotion is thought to have made ...

medicalxpress.com

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

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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.

www.washingtonpost.com

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.

www.bostonglobe.com

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.

eurekalert.org

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.

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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.

medicalxpress.com

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.

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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.

www.nature.com

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.

theconversation.com

Other Publications

Urpa, L., Kurki, M. I., Rahikkala, E., Hämäläinen, E., Salomaa, V., Suvisaari, J., Keski-Filppula, R., Rauhala, M., Korpi-Heikkilä, S., Komulainen-Ebrahim, J., Helander, H., Vieira, P., Uusimaa, J., Moilanen, J. S., Körkkö, J., Singh, T., Kuismin, O., Pietiläinen, O., Palotie, A., & Daly, M. J. (2024). Evidence for the additivity of rare and common variant burden throughout the spectrum of intellectual disability. European Journal of Human Genetics, 1–8.

Zhou, T., Ho, Y.-Y., Lee, R. X., Fath, A. B., He, K., Scott, J., Bajwa, N., Hartley, N. D., Wilde, J., Gao, X., Li, C., Hong, E., Nassar, M. R., Wimmer, R. D., Singh, T., Halassa, M. M., & Feng, G. (2024). Enhancement of mediodorsal thalamus rescues aberrant belief dynamics in a mouse model with schizophrenia-associated mutation. In bioRxiv (p. 2024.01. 08.574745). https://doi.org/10.1101/2024.01.08.574745

Flynn, B. I., Javan, E. M., Lin, E., Trutner, Z., Koenig, K., Anighoro, K. O., Kun, E., Gupta, A., Singh, T., Jayakumar, P., & Narasimhan, V. M. (2023). Deep learning based phenotyping of medical images improves power for gene discovery of complex disease. Npj Digital Medicine, 6(1), 1–12.

Chen, C.-Y., Tian, R., Ge, T., Lam, M., Sanchez-Andrade, G., Singh, T., Urpa, L., Liu, J. Z., Sanderson, M., Rowley, C., Ironfield, H., Fang, T., Biogen Biobank Team, SUPER-Finland study, Northern Finland Intellectual Disability study, Daly, M., Palotie, A., Tsai, E. A., Huang, H., … Runz, H. (2023). The impact of rare protein coding genetic variation on adult cognitive function. Nature Genetics, 55(6), 927–938.

Hsu, Y.-H. H., Pintacuda, G., Liu, R., Nacu, E., Kim, A., Tsafou, K., Petrossian, N., Crotty, W., Suh, J. M., Riseman, J., Martin, J. M., Biagini, J. C., Mena, D., Ching, J. K. T., Malolepsza, E., Li, T., Singh, T., Ge, T., Egri, S. B., … Lage, K. (2023). Using brain cell-type-specific protein interactomes to interpret neurodevelopmental genetic signals in schizophrenia. iScience, 106701, 106701. https://doi.org/10.1016/j.isci.2023.106701

Liu, D., Meyer, D., Fennessy, B., Feng, C., Cheng, E., Johnson, J. S., Park, Y. J., Rieder, M.-K., Ascolillo, S., de Pins, A., Dobbyn, A., Lebovitch, D., Moya, E., Nguyen, T.-H., Wilkins, L., Hassan, A., … Singh, T. … Psychiatric Genomics Consortium Phase 3 Targeted Sequencing of Schizophrenia Study Team, Burdick, K. E., Buxbaum, J. D., Charney, A. W. (2023). Schizophrenia risk conferred by rare protein-truncating variants is conserved across diverse human populations. Nature Genetics, 55(3), 369–376. https://doi.org/10.1038/s41588-023-01305-1

Flynn, B. I., Javan, E. M., Lin, E., Trutner, Z., Koenig, K., Anighoro, K. O., Kun, E., Gupta, A., Singh, T., Jayakumar, P., & Narasimhan, V. M. (2023). Deep learning based phenotyping of medical images improves power for gene discovery of complex disease. medRxiv, 2023–2003.

Cohen, B. M., Singh, T., Öngür, D., Konstantin, G. E., & Gardner, M. E. (2022). Clinical phenotypes of five patients with psychotic disorders carrying rare schizophrenia-associated loss-of-function variants. Schizophrenia Research, 250, 100–103. https://doi.org/10.1016/j.schres.2022.11.006

Nehme, R., Pietiläinen, O., Artomov, M., Tegtmeyer, M., Valakh, V., Lehtonen, L., Bell, C., Singh, T., Trehan, A., Sherwood, J., Manning, D., Peirent, E., Malik, R., Guss, E. J., Hawes, D., Beccard, A., Bara, A. M., Hazelbaker, D. Z., Zuccaro, E., … Eggan, K. (2022). The 22q11.2 region regulates presynaptic gene-products linked to schizophrenia. Nature Communications, 13(1), 3690. https://doi.org/10.1038/s41467-022-31436-8

Palmer, D. S., Howrigan, D. P., Chapman, S. B., Adolfsson, R., Bass, N., Blackwood, D., Boks, M. P. M., Chen, C.-Y., Churchhouse, C., Corvin, A. P., Craddock, N., Curtis, D., Di Florio, A., Dickerson, F., Freimer, N. B., Goes, F. S., Jia, X., Jones, I., Jones, L., …, Singh, T., … Neale, B. M. (2022). Exome sequencing in bipolar disorder identifies AKAP11 as a risk gene shared with schizophrenia. Nature Genetics, 54(5), 541–547. https://doi.org/10.1038/s41588-022-01034-x

Dejanovic, B., Wu, T., Tsai, M.-C., Graykowski, D., Gandham, V. D., Rose, C. M., Bakalarski, C. E., Ngu, H., Wang, Y., Pandey, S., Rezzonico, M. G., Friedman, B. A., Edmonds, R., De Mazière, A., Rakosi-Schmidt, R., Singh, T., Klumperman, J., Foreman, O., Chang, M. C., … Hanson, J. E. (2022). Complement C1q-dependent excitatory and inhibitory synapse elimination by astrocytes and microglia in Alzheimer’s disease mouse models. Nature Aging, 2(9), 837–850. https://doi.org/10.1038/s43587-022-00281-1

Nehme, R., Pietiläinen, O., Artomov, M., Tegtmeyer, M., Valakh, V., Lehtonen, L., Bell, C., Singh, T., Trehan, A., Sherwood, J., Manning, D., Peirent, E., Malik, R., Guss, E. J., Hawes, D., Beccard, A., Bara, A. M., Hazelbaker, D. Z., Zuccaro, E., … Eggan, K. (2022). The 22q11.2 region regulates presynaptic gene-products linked to schizophrenia. Nature Communications, 13(1), 3690. https://doi.org/10.1038/s41467-022-31436-8

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