A comprehensive screening of copy-number variability in dementia with Lewy bodies

The role of genetic variability in dementia with Lewy bodies (DLB) is now indisputable, however data regarding copy number variation (CNV) in this disease has been lacking. Here, we used whole genome genotyping of 1,454 DLB cases and 1,525 controls to assess copy number variability. We used two algorithms to confidently detect CNVs, performed a case-control association analysis, screened for candidate CNVs previously associated with DLB-related diseases, and performed a candidate gene approach to fully explore the data. We identified five CNV regions with a significant genome-wide association to DLB, two of these were only present in cases and absent from publicly available databases: one of the regions overlapped LAPTM4B, a known lysosomal protein; whilst the other overlapped the NME1 locus and SPAG9. We also identified DLB cases presenting CNVs in genes previously associated with DLB or related neurodegenerative diseases, namely SNCA andMAPT. To our knowledge, this is the first study reporting genome-wide CNVs in a large DLB cohort.