Increased CNV-Region Deletions in Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD) Subjects in the ADNI Sample

Authors

Guia Guffanti, Columbia UniversityFollow
Federica Torri, University of California, IrvineFollow
Jerod Rasmussen, University of California, IrvineFollow
Andrew P. Clark, University of Southern CaliforniaFollow
Anita Lakatos, University of California, IrvineFollow
Jessica Turner, Georgia State UniversityFollow
James H. Fallon, University of California, IrvineFollow
Andew Saykin, Indiana University Purdue University IndianapolisFollow
Michael Weiner, University of California, San FranciscoFollow
Marquis P. Vawter, University of California, IrvineFollow
James A. Knowles, University of Southern CaliforniaFollow
Steven G. Potkin, University of Southern CaliforniaFollow
Fabio Macciardi, University of California, IrvineFollow

Document Type

Article

Publication Date

4-2013

Abstract

We investigated the genome-wide distribution of CNVs in the Alzheimer's disease (AD) Neuroimaging Initia- tive (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 hetero- zygous deletions in cases (p-value b 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 con- firmed 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.

Comments

Originally Published in:

Genomics. 2013 Aug;102(2):112-22. doi: http://dx.doi.org/10.1016/j.ygeno.2013.04.004

Recommended Citation

Guffanti G, Torri F, Rasmussen J, Clark AP, Lakatos A, Turner JA, Fallon JH, Saykin AJ, Weiner M; ADNI the Alzheimer's Disease Neuroimaging Initiative, Vawter MP, Knowles JA, Potkin SG, Macciardi F.. Increased CNV-Region Deletions in Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD) Subjects in the ADNI Sample. Genomics. 2013 Aug;102(2):112-22. doi: http://dx.doi.org/10.1016/j.ygeno.2013.04.004

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