Genome-wide copy-number variation study of psychosis in Alzheimer’s disease

About 40–60% of patients with late-onset Alzheimer’s disease (AD) develop psychosis, which represents a distinct phenotype of more severe cognitive and functional deficits. The estimated heritability of AD+P is ~61%, which makes it a good target for genetic mapping. We performed a genome-wide copy-n...

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Veröffentlicht in:Translational psychiatry 2015-06, Vol.5 (6), p.e574-e574
Hauptverfasser: Zheng, X, Demirci, F Y, Barmada, M M, Richardson, G A, Lopez, O L, Sweet, R A, Kamboh, M I, Feingold, E
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Sprache:eng
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Zusammenfassung:About 40–60% of patients with late-onset Alzheimer’s disease (AD) develop psychosis, which represents a distinct phenotype of more severe cognitive and functional deficits. The estimated heritability of AD+P is ~61%, which makes it a good target for genetic mapping. We performed a genome-wide copy-number variation (CNV) study on 496 AD cases with psychosis (AD+P), 639 AD subjects with intermediate psychosis (AD intermediate P) and 156 AD subjects without psychosis (AD−P) who were recruited at the University of Pittsburgh Alzheimer's Disease Research Center using over 1 million single-nucleotide polymorphisms (SNPs) and CNV markers. CNV load analysis found no significant difference in total and average CNV length and CNV number in the AD+P or AD intermediate P groups compared with the AD−P group. Our analysis revealed a marginally significant lower number of duplication events in AD+P cases compared with AD−P controls ( P =0.059) using multivariable regression model. The most interesting finding was the presence of a genome-wide significant duplication in the APC2 gene on chromosome 19, which was protective against developing AD+P (odds ratio=0.42; P =7.2E−10). We also observed suggestive associations of duplications with AD+P in the SET ( P =1.95E−06), JAG2 ( P =5.01E−07) and ZFPM1 ( P =2.13E−07) genes and marginal association of a deletion in CNTLN ( P =8.87E−04). We have identified potential novel loci for psychosis in Alzheimer’s disease that warrant follow-up in large-scale independent studies.
ISSN:2158-3188
2158-3188
DOI:10.1038/tp.2015.64