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., Purushottam, M., & Mondal, M. Scientific reports, 11(1):21088, October, 2021. Place: England
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},
	copyright = {© 2021. The Author(s).},
	issn = {2045-2322},
	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.},
	language = {eng},
	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 Purushottam, Meera and Mondal, Mayukh},
	month = oct,
	year = {2021},
	pmid = {34702870},
	pmcid = {PMC8548332},
	note = {Place: England},
	keywords = {*Brain/growth \& development/immunology, *Exome Sequencing, *Mental Disorders/genetics/immunology, Animals, Female, Humans, Immunity, Innate/*genetics, Male, Neanderthals/genetics/immunology},
	pages = {21088},
}

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