Increased CNV-Region deletions in mild cognitive impairment (MCI) and Alzheimer's disease (AD) subjects in the ADNI sample

被引：22

作者：

Guffanti, Guia ^{[1
]}

Torri, Federica ^{[2
]}

Rasmussen, Jerod ^{[2
]}

Clark, Andrew P. ^{[3
,4
]}

Lakatos, Anita ^{[2
]}

Turner, Jessica A. ^{[5
]}

Fallon, James H. ^{[2
]}

Saykin, Andrew J. ^{[6
]}

Weiner, Michael ^{[7
]}

Vawter, Marquis P. ^{[2
,8
]}

Knowles, James A. ^{[3
,4
]}

Potkin, Steven G. ^{[2
]}

Macciardi, Fabio ^{[2
,9
,10
]}

机构：

[1] Columbia Univ NYSPI, Div Child & Adolescent Psychiat, Dept Psychiat, New York, NY 10032 USA

[2] Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92617 USA

[3] Univ So Calif, Dept Psychiat, Los Angeles, CA 90033 USA

[4] Univ So Calif, Zilkha Neurogenet Inst, Los Angeles, CA 90033 USA

[5] Mind Res Network, Albuquerque, NM 87106 USA

[6] Indiana Univ Sch Med, Dept Radiol Imaging Sci, Indianapolis, IN 46206 USA

[7] Univ Calif San Francisco, Dept Radiol Psychiat & Neurol, San Francisco, CA 94121 USA

[8] Univ Calif Irvine, Sch Med, Dept Psychiat & Human Behav, Funct Genom Lab, Irvine, CA 92697 USA

[9] Univ Calif Irvine, Sch Med, Ctr Epigenet & Metab, Irvine, CA 92617 USA

[10] Univ Milan, Dept Pharmacol & Biomol Sci, I-20122 Milan, Italy

来源：

GENOMICS | 2013年 / 102卷 / 02期

基金：

美国国家卫生研究院;

关键词：

Alzheimer's disease; Copy Number Variable Regions (CNV-Regions); Copy Number Variations (CNVs); Genome-wide scan; Next Generation Sequencing (NGS); COPY-NUMBER VARIATION; STRUCTURAL VARIATION; QUANTITATIVE TRAIT; VARIANTS; DNA; NETWORKS; GENES; IDENTIFICATION; REARRANGEMENTS; ASSOCIATION;

D O I：

10.1016/j.ygeno.2013.04.004

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

We investigated the genome-wide distribution of CNVs in the Alzheimer's disease (AD) Neuroimaging Initiative (ADNI) sample (146 with AD, 313 with Mild Cognitive Impairment (MCI), and 181 controls). Comparison of single CNVs between cases (MCI and AD) and controls shows overrepresentation of large heterozygous deletions in cases (p-value < 0.0001). The analysis of CNV-Regions identifies 44 copy number variable loci of heterozygous deletions, with more CNV-Regions among affected than controls (p = 0.005). Seven of the 44 CNV-Regions are nominally significant for association with cognitive impairment. We validated and confirmed our main findings with genome re-sequencing of selected patients and controls. The functional pathway analysis of the genes putatively affected by deletions of CNV-Regions reveals enrichment of genes implicated in axonal guidance, cell-cell adhesion, neuronal morphogenesis and differentiation. Our findings support the role of CNVs in AD, and suggest an association between large deletions and the development of cognitive impairment (C) 2013 Elsevier Inc. All rights reserved.

引用

页码：112 / 122

页数：11

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