Landscape of copy number variants in Spanish People with Dementia

Abstract

Abstract Background Recent studies suggest that copy number variants (CNVs) may contribute to the missing heritability of complex diseases such as Alzheimer’s disease (AD) and related dementias (ADRD). Methods We performed a CNV analysis using genotyping data (Axiom 815K Spanish biobank array) from the GR@ACE/DEGESCO dementia dataset (n=20,067) of the Spanish population. Applying PennCNV and extensive quality control, 8,275 controls and 7,818 dementia cases were selected for gene-level case/control associations. Results We identified 43,833 CNVs with deletions (47%) and duplications (53%). No genome-wide significant associations were found, but nominal associations were observed in PKP3 - SIGIRR and FBRSL1 loci. CNVs in 2,970 genes were exclusive to dementia cases, enriched in vascular-related pathways. Notable findings included 14q11.2 duplication and VPS13B deletions in ADRD cases, the latter confirmed by optical genome mapping. Conclusion Our findings suggest potential novel genes associated with ADRD in the Spanish population. However, the limited resolution of array-based technologies in detecting CNVs warrants further investigation.