RT Journal Article
SR Electronic
T1 Genome-Wide Association Study of Brain Connectivity Changes for Alzheimer’s Disease
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 342436
DO 10.1101/342436
A1 Samar S. M. Elsheikh
A1 Emile R. Chimusa
A1 Nicola J. Mulder
A1 Alessandro Crimi
YR 2019
UL http://biorxiv.org/content/early/2019/05/30/342436.abstract
AB Variations in the human genome have been found in the literature to be an essential factor that affects susceptibility to Alzheimer’s disease. Genome-wide association studies (GWAS) have identified genetic loci that significantly contribute to the risk of Alzheimers. The availability of genetic data, coupled with brain imaging technologies have left room for further discovery. Using data integration methodologies and new study designs. Although methods have been proposed for integrating image characteristics and genetic information towards studying Alzheimers, the measurement of disease is often taken at a single time point, therefore, not allowing the disease progression to be taken into consideration. In longitudinal settings, we analyzed neuroimaging and single nucleotide polymorphisms dataset obtained from the Alzheimer’s Disease Neuroimaging Initiative for three clinical stages of the disease, including controls, early mild cognitive impairment and Alzheimer’s Disease patients. We conducted a GWAS regressing the absolute change of specific global connectivity metrics on the genetic variants, and used the GWAS summary statistics to compute the gene and pathway scores. We observed significant associations between the change in structural brain connectivity and genes previously reported to biologically manipulate the risk and progression of certain neurodegenerative disorders, including Alzheimer’s disease.