Assessment of the genetic variance of late-onset Alzheimer's disease

Neurobiol Aging. 2016 May;41:200.e13-200.e20. doi: 10.1016/j.neurobiolaging.2016.02.024. Epub 2016 Mar 3.

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.

Keywords: Alzheimer's disease; Genetic variance; Genetics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / genetics*
  • Amyloid beta-Protein Precursor / genetics
  • Datasets as Topic
  • Female
  • Genetic Variation / genetics*
  • Genome-Wide Association Study*
  • Humans
  • Male
  • Membrane Glycoproteins / genetics
  • Netrin Receptors
  • Polymorphism, Single Nucleotide
  • Receptors, Cell Surface / genetics
  • Receptors, Immunologic / genetics
  • Risk

Substances

  • Amyloid beta-Protein Precursor
  • Membrane Glycoproteins
  • Netrin Receptors
  • Receptors, Cell Surface
  • Receptors, Immunologic
  • TREM2 protein, human
  • UNC5C protein, human

Grant support