期刊
NEUROBIOLOGY OF AGING
卷 41, 期 -, 页码 -出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2016.02.024
关键词
Alzheimer's disease; Genetics; Genetic variance
资金
- National Institutes of Health [R01AG042611]
- Brigham Young University Department of Biology
- National Institutes of Health, National Institute on Aging (NIH-NIA) [U01 AG032984, RC2 AG036528, U01 AG016976, U24 AG021886, U24 AG026395, R01AG041797]
- NINDS grant [NS39764]
- NIMH [MH60451]
- GlaxoSmithKline
- Kronos Science
- NIA [AG041232]
- Banner Alzheimer's Foundation
- Johnnie B. Byrd Sr. Alzheimer's Institute
- Medical Research Council
- state of Arizona
- Newcastle University
- Higher Education Funding Council for England (HEFCE)
- Alzheimer's Research Trust (ART)
- BRACE
- North Bristol NHS Trust Research and Innovation Department
- DeNDRoN
- Stichting MS Research
- Brain Net Europe
- Hersenstichting Nederland Breinbrekend Werk
- International Parkinson Fonds
- Internationale Stiching Alzheimer Onderzoek
- Department of Defense [W81XWH-12-2-0012]
- National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering
- Canadian Institutes of Health Research
- Alzheimer's Association [IIRG-08-89720, IIRG-05-14147]
- U.S. Department of Veterans Affairs Administration, Office of Research and Development, Biomedical Laboratory Research Program
- Wellcome Trust
- Howard Hughes Medical Institute
- Canadian Institute of Health Research
Alzheimer's disease (AD) is a complex genetic disorder with no effective treatments. More than 20 common markers have been identified, which are associated with AD. Recently, several rare variants have been identified in Amyloid Precursor Protein (APP), Triggering Receptor Expressed On Myeloid Cells 2 (TREM2) and Unc-5 Netrin Receptor C (UNC5C) that affect risk for AD. Despite the many successes, the genetic architecture of AD remains unsolved. We used Genome-wide Complex Trait Analysis to (1) estimate phenotypic variance explained by genetics; (2) calculate genetic variance explained by known AD single nucleotide polymorphisms (SNPs); and (3) identify the genomic locations of variation that explain the remaining unexplained genetic variance. In total, 53.24% of phenotypic variance is explained by genetics, but known AD SNPs only explain 30.62% of the genetic variance. Of the unexplained genetic variance, approximately 41% is explained by unknown SNPs in regions adjacent to known AD SNPs, and the remaining unexplained genetic variance outside these regions. (C) 2016 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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