66 Scopus citations

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 languageEnglish
Pages (from-to)200.e13-200.e20
JournalNeurobiology of Aging
Volume41
DOIs
StatePublished - 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 .

FundersFunder number
National Institutes of Health (NIH)
Brigham Young University Department of Biology
National Institute on AgingP50AG005144, 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 InstituteU01HG008657, U01HG006375, U01HG004610
National Human Genome Research Institute
Institute of Neurological Disorders and Stroke National Advisory Neurological Disorders and Stroke CouncilR01NS059873, P50NS039764
Institute of Neurological Disorders and Stroke National Advisory Neurological Disorders and Stroke Council
National Childhood Cancer Registry – National Cancer InstituteR01CA129769
National Childhood Cancer Registry – National Cancer Institute
U.S. Department of Veterans AffairsIK2BX001820
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 HealthP50MH060451, R01MH080295
National Institute of Mental Health
National Center for Research ResourcesM01RR000096, 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

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