Abstract
Alzheimer’s Disease (AD) is a progressive neurologic disease and the most common form of dementia. While the causes of AD are not completely understood, genetics plays a key role in the etiology of AD, and thus finding genetic factors holds the potential to uncover novel AD mechanisms. For this study, we focus on copy number variation (CNV) detection and burden analysis. Leveraging whole-genome sequence (WGS) data released by Alzheimer’s Disease Sequencing Project (ADSP), we developed a scalable bioinformatics pipeline to identify CNVs. This pipeline was applied to 1,737 AD cases and 2,063 cognitively normal controls. As a result, we observed 237,306 and 42,767 deletions and duplications, respectively, with an average of 2,255 deletions and 1,820 duplications per subject. The burden tests show that Non-Hispanic-White cases on average have 16 more duplications than controls do (p-value 2e-6), and Hispanic cases have larger deletions than controls do (p-value 6.8e-5).
Highlights
Alzheimer’s disorder (AD) is a devastating neurodegenerative disease and is the most common cause of dementia
Alzheimer’s Disease (AD) heritability estimates range from 49–79%;
We reported the copy number variation (CNV) burdens for AA, Hispanic, and Non-Hispanic White (NHW) separately as well as for all-combined samples (ALL), The Bonferroni threshold for multiple testing is p-value < 0.05/96 analyses 0.000521, where the 96 analyses included the combinations from 2 sets of CNV analyses, 4 burden features, 3 CNV events (DelDup, deletions specific (Del), and duplications specific (Dup)) and 4 sample groups (ALL, AA, Hispanic, and NHW)
Summary
Alzheimer’s disorder (AD) is a devastating neurodegenerative disease and is the most common cause of dementia. Taking copy number variation (CNV) into consideration may partially mitigate the problem of missing heritability and play an important role in human disease susceptibility (Cooper et al, 2011; Chung et al, 2014; McCarroll and Altshuler, 2007; Kakinuma and Sato, 2008; Cooper et al, 2011; Chung et al, 2014; McCarroll and Altshuler, 2007; Kakinuma and Sato, 2008). There is no comprehensive genome-wide CNV study using whole-genome sequence (WGS) to enhance the knowledge of AD etiology and risk
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