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Comparative Study
. 2010;19(1):69-77.
doi: 10.3233/JAD-2010-1212.

Genome-wide scan of copy number variation in late-onset Alzheimer's disease

Erin L Heinzen  1 , Anna C Need, Kathleen M Hayden, Ornit Chiba-Falek, Allen D Roses, Warren J Strittmatter, James R Burke, Christine M Hulette, Kathleen A Welsh-Bohmer, David B Goldstein
Affiliations
Comparative Study

Genome-wide scan of copy number variation in late-onset Alzheimer's disease

Erin L Heinzen et al. J Alzheimers Dis. 2010.

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 epsilon4 risk allele, identified a novel variant that influences disease risk within the APOE epsilon4 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.

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Figures

Fig. 1
Fig. 1
A quantile-quantile-plot of transformed P-values (using the inverse chi-square distribution with 1 degree of freedom) against the expected transformed p values. The solid black line indicates the correlation expected by random chance. High correlation of expected versus observed for > 90% of p values indicates full correction for population stratification. (Colours are visible in the electronic version of the article at www.iospress.nl.)
Fig. 2
Fig. 2
Genome overview of −log p values for all SNPs evaluated in this scan. Red dot on chromosome 9 is a SNP located in the TOMM40, a gene upstream of APOE ε4. This SNP, located in a gene upstream of APOε4 gene, tags the previously documented APOE ε4 risk haplotype. (Colours are visible in the electronic version of the article at www.iospress.nl.)
Fig. 3
Fig. 3
(A) 15q13.3 duplication enriched in patients with Alzheimer’s disease. (B) Representative image of the b allele frequency and log R ratios (quantitative assessments of genotyping used to determine CNV) for a patient with a duplication of CHRNA7. SNPs included in the duplication are highlighted in red. (Colours are visible in the electronic version of the article at www.iospress.nl.)
See this image and copyright information in PMC

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