Abstract
Rapid progress has been made in identifying rare and common ‘polygenic’ genetic variants for neurodevelopmental disorders, which can have incomplete or variable penetrance. Whilst these studies provide insights into putative molecular networks affected, the phenotypes examined are almost universally based on behavioral symptoms manifested by children and adults. At present, there exists a ‘black hole’ in our ability to build mechanistic models of the effect of genetic variation on early brain development, and the mechanisms by which apparently unaffected carriers functionally compensate for increased genetic risk.
The proposed project will utilize detailed neurocognitive and behavioral measures on ~150 infants at-risk of neurodevelopmental disorders to test the hypothesis that clinically unaffected individuals at high genetic risk show atypical cognitive and/or behavioral development. It will also examine whether candidate protective factors can ameliorate the effects of high genetic risk.
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