Abstract
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.
Original language | English |
---|---|
Pages (from-to) | 200.e13-200.e20 |
Journal | Neurobiology of Aging |
Volume | 41 |
DOIs | |
State | Published - May 1 2016 |
Bibliographical note
Publisher Copyright:© 2016 The Authors.
Funding
Support for this project was provided by the National Institutes of Health ( R01AG042611 ) and the Brigham Young University Department of Biology .
Funders | Funder number |
---|---|
National Institutes of Health (NIH) | |
Brigham Young University Department of Biology | |
National Institute on Aging | P50AG005144, R01AG033193, P50AG005146, RF1AG015819, P50AG005142, R01AG035137, U01AG024904, U24AG021886, R01AG019085, R01AG025259, U01AG016976, P01AG010491, R01AG013616, RC2AG036528, P50AG005133, P50AG005134, R01AG012101, P50AG005131, P30AG013854, P30AG028383, R01AG027944, P50AG016582, U01AG010483, P50AG005136, R01AG022374, P50AG025688, P50AG005138, P50AG023501, R01AG041232, R01AG041797, R01AG021547, P50AG005681, P50AG008671, P30AG028377, R37AG015473, R01AG041718, R01AG026916, R01AG030146, P01AG019724, U01AG006781, P50AG033514, P50AG016573, P50AG016574, P30AG013846, P30AG010133, R01AG030653, P50AG016570, R01AG017917, P01AG002219, P50AG005128, R01AG007562, U01AG032984, R01AG042611, RC2AG036502, R01AG019757, R01AG020688, R01AG017173, R01AG031581, P30AG008017, U24AG026395, P30AG010124, P30AG012300, P30AG010161, U24AG041689, P01AG003991, P30AG010129, P30AG019610, P30AG008051, P50AG008702 |
National Institute on Aging | |
National Human Genome Research Institute | U01HG008657, U01HG006375, U01HG004610 |
National Human Genome Research Institute | |
Institute of Neurological Disorders and Stroke National Advisory Neurological Disorders and Stroke Council | R01NS059873, P50NS039764 |
Institute of Neurological Disorders and Stroke National Advisory Neurological Disorders and Stroke Council | |
National Childhood Cancer Registry – National Cancer Institute | R01CA129769 |
National Childhood Cancer Registry – National Cancer Institute | |
U.S. Department of Veterans Affairs | IK2BX001820 |
U.S. Department of Veterans Affairs | |
National Center for Advancing Translational Sciences (NCATS) | UL1TR001445 |
National Center for Advancing Translational Sciences (NCATS) | |
National Institute of Mental Health | P50MH060451, R01MH080295 |
National Institute of Mental Health | |
National Center for Research Resources | M01RR000096, UL1RR029893 |
National Center for Research Resources |
Keywords
- Alzheimer's disease
- Genetic variance
- Genetics
ASJC Scopus subject areas
- General Neuroscience
- Aging
- Clinical Neurology
- Developmental Biology
- Geriatrics and Gerontology