Genome-Wide Scan of Copy Number Variation in Late-Onset Alzheimer's Disease

Issue title: Similarities and Differences Between Mild Cognitive Impairment and Alzheimer's Disease

Guest editors: Mark A. Lovell

Article type: Research Article

Authors: Heinzen, Erin L.^{a; *} | Need, Anna C.^a | Hayden, Kathleen M.^b | Chiba-Falek, Ornit^{a; b; c} | Roses, Allen D.^d | Strittmatter, Warren J.^c | Burke, James R.^{b; c} | Hulette, Christine M.^b | Welsh-Bohmer, Kathleen A.^b | Goldstein, David B.^a

Affiliations: [a] Institute for Genome Sciences & Policy, Center for Human Genome Variation, Duke University, Durham, NC, USA | [b] Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University, Durham, NC, USA | [c] Division of Neurology, Department of Medicine, Duke University Medical Center, Durham, NC, USA | [d] Department of Medicine [Neurology], Director, Deane Drug Discovery Institute, Duke Institute for Genome Sciences and Policy, Durham, NC, USA | Sanders-Brown Center on Aging and Alzheimer's Disease Center, Department of Chemistry, University of Kentucky, Lexington, Kentucky, USA

Correspondence: [*] Corresponding author: Erin L. Heinzen, Duke University Medical Center, 450 Research Drive, LSRC B Wing, Box 91009, Durham, NC 27708, USA. Tel.: +1 919 684 8684; Fax: +1 919 668 6787; E-mail: [email protected].

Abstract: Alzheimer's disease is a complex and progressive neurodegenerative disease leading to loss of memory, cognitive impairment, and ultimately death. To date, six large-scale genome-wide association studies have been conducted to identify SNPs that influence disease predisposition. These studies have confirmed the well-known APOE ε4 risk allele, identified a novel variant that influences disease risk within the APOE ε4 population, found a SNP that modifies the age of disease onset, as well as reported the first sex-linked susceptibility variant. Here we report a genome-wide scan of Alzheimer's disease in a set of 331 cases and 368 controls, extending analyses for the first time to include assessments of copy number variation. In this analysis, no new SNPs show genome-wide significance. We also screened for effects of copy number variation, and while nothing was significant, a duplication in CHRNA7 appears interesting enough to warrant further investigation.

Keywords: Alzheimer's disease, copy number variation, dementia, genome-wide association study

DOI: 10.3233/JAD-2010-1212

Journal: Journal of Alzheimer's Disease, vol. 19, no. 1, pp. 69-77, 2010