Analysis of copy number variation in a Turkish dementia cohort

Background Copy number variations (CNVs) arise from copied or deleted regions of the genome. These regions vary in size and may span genes known to play a role in human disease. For example, duplications and triplications of SNCA have been shown to cause forms of Parkinson’s disease, while extra copies of APP are associated with early onset Alzheimer’s disease (AD). We have previously studied a Turkish dementia cohort for variants in known disease‐causing genes for both AD and frontotemporal dementia (FTD) and have also reported variants in the new AD‐associated genes TREM2 and NOTCH3. The goal of the current study was to perform a systematic analysis of CNVs in order to further characterize the genetic causes of dementia in this Turkish dementia cohort. Method Ninety‐nine Turkish individuals, either at risk of dementia due to family history, diagnosed with mild cognitive impairment, AD or FTD, were whole‐genome genotyped using Illumina HumanOmniExpress chips. We used GenomeStudio cnvPartition v3.2.1 plug‐in (Illumina, Inc) to analyze the data. Result We did not identify any CNVs segregating with disease in any of the four dementia families present in the studied cohort. We also did not observe any CNVs across our entire data set overlapping genes which have been previously associated with neurodegenerative diseases. We identified 9 distinct CNVs overlapping regions previously reported to have potential disease‐associated gene dosage alterations in patients with dementia phenotypes using PennCNV‐1.0.5; these were confirmed by manually checking CNVs on GenomeStudio. We observed potential disease‐associated CNVs in single individuals overlapping LOC286367, ABCA1, NIPSNAP3A, NIPSNAP3B, OR13C2, OR13C5, OR13C8, OR13C9, OR13D1, CNTN6, NIPA1, CYFIP1, GALNTL6, NLGN1, XPO1, SNORA70B, USP34, and HLA‐G. Additionally, two identical heterozygous duplications spanning MICA were identified in two AD patients; CNVs spanning this gene have been previously reported in four AD patients and no controls. Conclusion In this study, we integrated whole‐genome genotyping results from a Turkish cohort with previously reported findings and data publicly available to add further evidence to the role of specific CNVs in the pathogenesis of dementia.