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Genes To Mental Health (G2MH): A framework to map the combined effects of rare and common variants on dimensions of cognition and psychopathology

Jacquemont, Sébastien, Huguet, Guillaume, Klein, Marieke, Chawner, Samuel J.R.A., Donald, Kirsten A., van den Bree, Marianne B.M., Sebat, Jonathan, Ledbetter, David H., Constantino, John, Earl, Rachel K., McDonald-McGinn, Donna, van Amelsvoort, Therese, Swillen, Ann, O'Donnell-Luria, Anne H, Glahn, David C., Almasy, Laura, Scherer, Stephen, Robinson, Elise, Bassett, Anne S., Martin, Christa L., Finucane, Brenda, Vorstman, Jacob A.S., Bearden, Carrie E. and Gur, Raquel E. 2022. Genes To Mental Health (G2MH): A framework to map the combined effects of rare and common variants on dimensions of cognition and psychopathology. American Journal of Psychiatry 179 (3) , pp. 189-203. 10.1176/appi.ajp.2021.21040432

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Rare genomic disorders (RGDs) confer elevated risk for neurodevelopmental psychiatric disorders. In this era of intense genomics discoveries, the landscape of RGDs is rapidly evolving. However, there has not been comparable progress to date in scalable, harmonized phenotyping methods. As a result, beyond associations with categorical diagnoses, the effects on dimensional traits remain unclear for many RGDs. The nature and specificity of RGD effects on cognitive and behavioral traits is an area of intense investigation: RGDs are frequently associated with more than one psychiatric condition, and those studied to date affect, to varying degrees, a broad range of developmental and cognitive functions. Although many RGDs have large effects, phenotypic expression is typically influenced by additional genomic and environmental factors. There is emerging evidence that using polygenic risk scores in individuals with RGDs offers opportunities to refine prediction, thus allowing for the identification of those at greatest risk of psychiatric illness. However, translation into the clinic is hindered by roadblocks, which include limited genetic testing in clinical psychiatry, and the lack of guidelines for following individuals with RGDs, who are at high risk of developing psychiatric symptoms. The Genes to Mental Health Network (G2MH) is a newly funded National Institute of Mental Health initiative that will collect, share, and analyze large-scale data sets combining genomics and dimensional measures of psychopathology spanning diverse populations and geography. The authors present here the most recent understanding of the effects of RGDs on dimensional behavioral traits and risk for psychiatric conditions and discuss strategies that will be pursued within the G2MH network, as well as how expected results can be translated into clinical practice to improve patient outcomes.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Psychology
Cardiff University Centre for Human Development Science (CHDS)
Publisher: American Psychiatric Publishing
ISSN: 0002-953X
Date of First Compliant Deposit: 23 September 2021
Date of Acceptance: 23 August 2021
Last Modified: 15 Mar 2022 14:47

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