Identification of neurodevelopmental gene variants implicated in age‐related brain morphological changes and cortical atrophy

Background Neurodevelopmental genes and their associated protein products are involved in a number of biological processes essential for brain assembly. Despite their relative importance, the impact of genetic variation in neurodevelopmental genes on the neurodegenerative and neurocognitive changes that occur in Alzheimer’s disease, is poorly characterised. Here, we investigated the associations between Single Nucleotide Polymorphisms (SNPs) in neurodevelopmental genes and brain volumetrics. Method From a curated list of 40 genes related to neurodevelopmental processes, we identified a set of 233 independent SNPs. The genotype data was generated from 715 unrelated individuals (Amyloid Beta (Ab) ‐ N=328, Ab+ N=387), enrolled in the Australian Imaging, Biomarker & Lifestyle (AIBL) study. We focused this research on the cortical grey, subcortical white matter, ventricular, and hippocampal volumes and used linear mixed models to assess whether specific genotypes were associated to regional volume changes over time. The associations with the traits of interest were assessed cross‐sectionally at baseline and longitudinally, over a 12‐year time span. Result At baseline, cross‐sectional analyses revealed one significant association between the variant, rs2923137, located in DRC7 (