Analysis of whole exome sequencing in severe mental illness hints at selection of brain development and immune related genes. Mahadevan, J., Pathak, A. K., Vemula, A., Nadella, R. K., Viswanath, B., Jain, S., Rao, N. P., Narayanaswamy, J. C., Viswanath, B., Sivakumar, P. T., Kandasamy, A., Kesavan, M., Mehta, U. M., Venkatasubramanian, G., John, J. P., Purushottam, M., Mukherjee, O., Kannan, R., Mehta, B., Kandavel, T., Binukumar, B., Saini, J., Jayarajan, D., Shyamsundar, A., Moirangthem, S., Kumar, K. G. V., Holla, B., Mahadevan, J., Thirthalli, J., Chandra, P. S., Gangadhar, B. N., Murthy, P., Panicker, M. M., Bhalla, U. S., Chattarji, S., Benegal, V., Varghese, M., Reddy, J. Y. C., Jain, S., Raghu, P., Rao, M., Purushottam, M., Mondal, M., & Accelerator Program for Discovery in Brain disorders using Stem cells (ADBS) Consortium Scientific Reports, 11(1):21088, October, 2021. Number: 1
Analysis of whole exome sequencing in severe mental illness hints at selection of brain development and immune related genes [link]Paper  doi  abstract   bibtex   
Evolutionary trends may underlie some aspects of the risk for common, non-communicable disorders, including psychiatric disease. We analyzed whole exome sequencing data from 80 unique individuals from India coming from families with two or more individuals with severe mental illness. We used Population Branch Statistics (PBS) to identify variants and genes under positive selection and identified 74 genes as candidates for positive selection. Of these, 20 were previously associated with Schizophrenia, Alzheimer’s disease and cognitive abilities in genome wide association studies. We then checked whether any of these 74 genes were involved in common biological pathways or related to specific cellular or molecular functions. We found that immune related pathways and functions related to innate immunity such as antigen binding were over-represented. We also evaluated for the presence of Neanderthal introgressed segments in these genes and found Neanderthal introgression in a single gene out of the 74 candidate genes. However, the introgression pattern indicates the region is unlikely to be the source for selection. Our findings hint at how selection pressures in individuals from families with a history of severe mental illness may diverge from the general population. Further, it also provides insights into the genetic architecture of severe mental illness, such as schizophrenia and its link to immune factors.
@article{mahadevan_analysis_2021,
	title = {Analysis of whole exome sequencing in severe mental illness hints at selection of brain development and immune related genes},
	volume = {11},
	issn = {2045-2322},
	url = {https://doi.org/10.1038/s41598-021-00123-x},
	doi = {10.1038/s41598-021-00123-x},
	abstract = {Evolutionary trends may underlie some aspects of the risk for common, non-communicable disorders, including psychiatric disease. We analyzed whole exome sequencing data from 80 unique individuals from India coming from families with two or more individuals with severe mental illness. We used Population Branch Statistics (PBS) to identify variants and genes under positive selection and identified 74 genes as candidates for positive selection. Of these, 20 were previously associated with Schizophrenia, Alzheimer’s disease and cognitive abilities in genome wide association studies. We then checked whether any of these 74 genes were involved in common biological pathways or related to specific cellular or molecular functions. We found that immune related pathways and functions related to innate immunity such as antigen binding were over-represented. We also evaluated for the presence of Neanderthal introgressed segments in these genes and found Neanderthal introgression in a single gene out of the 74 candidate genes. However, the introgression pattern indicates the region is unlikely to be the source for selection. Our findings hint at how selection pressures in individuals from families with a history of severe mental illness may diverge from the general population. Further, it also provides insights into the genetic architecture of severe mental illness, such as schizophrenia and its link to immune factors.},
	number = {1},
	journal = {Scientific Reports},
	author = {Mahadevan, Jayant and Pathak, Ajai Kumar and Vemula, Alekhya and Nadella, Ravi Kumar and Viswanath, Biju and Jain, Sanjeev and Rao, Naren P. and Narayanaswamy, Janardhanan C. and Viswanath, Biju and Sivakumar, Palanimuthu T. and Kandasamy, Arun and Kesavan, Muralidharan and Mehta, Urvakhsh Meherwan and Venkatasubramanian, Ganesan and John, John P. and Purushottam, Meera and Mukherjee, Odity and Kannan, Ramakrishnan and Mehta, Bhupesh and Kandavel, Thennarasu and Binukumar, B. and Saini, Jitender and Jayarajan, Deepak and Shyamsundar, A. and Moirangthem, Sydney and Kumar, K. G. Vijay and Holla, Bharath and Mahadevan, Jayant and Thirthalli, Jagadisha and Chandra, Prabha S. and Gangadhar, Bangalore N. and Murthy, Pratima and Panicker, Mitradas M. and Bhalla, Upinder S. and Chattarji, Sumantra and Benegal, Vivek and Varghese, Mathew and Reddy, Janardhan Y. C. and Jain, Sanjeev and Raghu, Padinjat and Rao, Mahendra and Purushottam, Meera and Mondal, Mayukh and {Accelerator Program for Discovery in Brain disorders using Stem cells (ADBS) Consortium}},
	month = oct,
	year = {2021},
	note = {Number: 1},
	pages = {21088},
}
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