Knowledge about genetic susceptibility factors in neuropsychiatric diseases has evolved quickly over the past years. Nevertheless, it is still incomplete. Lists of genes implicated in those disorders are not exhaustive while the risk level held by each pathogenic genetic variant, as well as their interactions, are not fully understood. Our team focuses on two common and distinct diseases, carrying an important burden for the society, Alzheimer disease and Autism spectrum disorder. Both disorders are extremely different but share a common determinism: they are considered as complex disorders in the majority of cases with a high genetic component.
For both disorders, we built a cohort of patients and performed whole exome sequencing, i.e. the sequencing of all the coding regions of the genome. We aim to find novel genes with an excess of rare deleterious genetic variants in cases, independently for each disease, as compared to controls representative of the general populations from the UK biobank dataset. Thus, by increasing the list of genes associated with those neuropsychiatric disorders, this project can improve the genetic diagnostics capabilities in a clinical setting in the future.
In addition and unlike ASD, AD is an age-related disorder. Hence, the probability of developing the disease at a given age when carrying certain genetic variants is very important for the future of AD medical prevention. We will use the UKbiobank in comparison to other published resources to refine our estimations of the penetrance of rare genetic variants from well-known associated genes (such as ABCA7, SORL1 and TREM2).
Lastly, we plan to integrate these data with common polygenic risk to decipher the roles of common and rare risk factors in the genetic architecture of these disorders..
