Background: Copy number variations (CNVs) play an important role in the genetic etiology of various neurological disorders, including Alzheimer's disease (AD). Type 2 diabetes mellitus (T2DM) and major depressive disorder (MDD) were shown to have share mechanisms and signaling pathways with AD.
Objective: We aimed to assess CNVs regions that may harbor genes contributing to AD, T2DM, and MDD in 67 Saudi familial and sporadic AD patients, with no alterations in the known genes of AD and genotyped previously for APOE.
Methods: DNA was analyzed using the CytoScan-HD array. Two layers of filtering criteria were applied. All the identified CNVs were checked in the Database of Genomic Variants (DGV).
Results: A total of 1086 CNVs (565 gains and 521 losses) were identified in our study. We found 73 CNVs harboring genes that may be associated with AD, T2DM or MDD. Nineteen CNVs were novel. Most importantly, 42 CNVs were unique in our studied cohort existing only in one patient. Two large gains on chromosomes 1 and 13 harbored genes implicated in the studied disorders. We identified CNVs in genes that encode proteins involved in the metabolism of amyloid-β peptide (AGRN, APBA2, CR1, CR2, IGF2R, KIAA0125, MBP, RER1, RTN4R, VDR and WISPI) or Tau proteins (CACNAIC, CELF2, DUSP22, HTRA1 and SLC2A14).
Conclusion: The present work provided information on the presence of CNVs related to AD, T2DM, and MDD in Saudi Alzheimer's patients.
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Association between major depressive disorder or depressive symptoms and the risk of vascular complications among patients with type 2 diabetes, and the mediating role of metabolic biomarkers: an analysis of the UK Biobank cohort.
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