title: Assessment of the genetic variance of late-onset Alzheimer's disease.
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.
authors.affiliation: Department of Biology, Brigham Young University, Provo, UT, USA.
authors.forename: Perry G
authors.initials: PG
authors.lastname: Ridge
authors.affiliation: Department of Biology, Brigham Young University, Provo, UT, USA.
authors.forename: Kaitlyn B
authors.initials: KB
authors.lastname: Hoyt
authors.affiliation: Department of Biology, Brigham Young University, Provo, UT, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Boehme
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Shubhabrata
authors.initials: S
authors.lastname: Mukherjee
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Paul K
authors.initials: PK
authors.lastname: Crane
authors.affiliation: Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Haines
authors.affiliation: Department of Neurology and the Taub Institute on Alzheimer's Disease and the Aging Brain, Gertrude H. Sergievsky Center, Columbia University, New York, NY, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Mayeux
authors.affiliation: Department of Biostatistics, Boston University, Boston, MA, USA; Department of Epidemiology, Boston University, Boston, MA, USA; Department of Medicine (Genetics Program), Boston University, Boston, MA, USA; Department of Neurology, Boston University, Boston, MA, USA; Department of Ophthalmology, Boston University, Boston, MA, USA.
authors.forename: Lindsay A
authors.initials: LA
authors.lastname: Farrer
authors.affiliation: Dr. John T. Macdonald Foundation Department of Human Genetics, and The John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL, USA.
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Pericak-Vance
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
authors.forename: Gerard D
authors.initials: GD
authors.lastname: Schellenberg
authors.affiliation: Department of Biology, Brigham Young University, Provo, UT, USA. Electronic address: kauwe@byu.edu.
authors.forename: John S K
authors.initials: JSK
authors.lastname: Kauwe
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D066264:Datasets as Topic; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D000075386:Netrin Receptors; D020641:Polymorphism, Single Nucleotide; D011956:Receptors, Cell Surface / Q000235:genetics; D011971:Receptors, Immunologic / Q000235:genetics; D012306:Risk
chemical_list: D016564:Amyloid beta-Protein Precursor; D008562:Membrane Glycoproteins; D000075386:Netrin Receptors; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C498715:TREM2 protein, human; C115727:UNC5C protein, human
keywords: Alzheimer's disease; Genetic variance; Genetics