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

• DOI: 10.1038/tp.2015.64
• Publication Date: 2015-06-02T13:45:24Z
• Authors: X Zheng; F Y Demirci; M M Barmada; G A Richardson; O L Lopez; R A Sweet; M I Kamboh; E Feingold
• Keywords: Genome-wide Association Study

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