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

Alzheimer's Disease Genetics Consortium (ADGC)

Research output: Contribution to journalArticle

18 Citations (Scopus)

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 (US)
Pages (from-to)200.e13-200.e20
JournalNeurobiology of Aging
Volume41
DOIs
StatePublished - May 1 2016

Fingerprint

Alzheimer Disease
Single Nucleotide Polymorphism
Inborn Genetic Diseases
Amyloid beta-Protein Precursor
Myeloid Cells
Genome

Keywords

  • Alzheimer's disease
  • Genetic variance
  • Genetics

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Aging
  • Developmental Biology
  • Geriatrics and Gerontology

Cite this

Assessment of the genetic variance of late-onset Alzheimer's disease. / Alzheimer's Disease Genetics Consortium (ADGC).

In: Neurobiology of Aging, Vol. 41, 01.05.2016, p. 200.e13-200.e20.

Research output: Contribution to journalArticle

Alzheimer's Disease Genetics Consortium (ADGC). / Assessment of the genetic variance of late-onset Alzheimer's disease. In: Neurobiology of Aging. 2016 ; Vol. 41. pp. 200.e13-200.e20.
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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.",
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author = "{Alzheimer's Disease Genetics Consortium (ADGC)} and Adams, {Perrie M.} and Albert, {Marilyn S.} and Albin, {Roger L.} and Apostolova, {Liana G.} and Arnold, {Steven E.} and Sanjay Asthana and Atwood, {Craig S.} and Baldwin, {Clinton T.} and Barber, {Robert C.} and Barmada, {Michael M.} and Barnes, {Lisa L.} and Sandra Barral and Beach, {Thomas G.} and Becker, {James T.} and Beecham, {Gary W.} and Duane Beekly and Bennett, {David A.} and Bigio, {Eileen H.} and Bird, {Thomas D.} and Deborah Blacker and Boeve, {Bradley F.} and Bowen, {James D.} and Adam Boxer and Burke, {James R.} and Burns, {Jeffrey M.} and Buxbaum, {Joseph D.} and Cairns, {Nigel J.} and Cantwell, {Laura B.} and Chuanhai Cao and Carlson, {Chris S.} and Carlsson, {Cynthia M.} and Carney, {Regina M.} and Carrasquillo, {Minerva M.} and Carroll, {Steven L.} and Chui, {Helena C.} and Clark, {David G.} and Jason Corneveaux and David, {Cribbs H.} and Crocco, {Elizabeth A.} and Carlos Cruchaga and {De Jager}, {Philip L.} and Charles DeCarli and {Yesim Demirci}, F. and Malcolm Dick and Dickson, {Dennis W.} and Doody, {Rachelle S.} and Jeffrey Kaye and Aimee Pierce and Joseph Quinn and Woltjer, {Randall (Randy)}",
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AU - Apostolova, Liana G.

AU - Arnold, Steven E.

AU - Asthana, Sanjay

AU - Atwood, Craig S.

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AU - Barmada, Michael M.

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AU - Bennett, David A.

AU - Bigio, Eileen H.

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AU - Blacker, Deborah

AU - Boeve, Bradley F.

AU - Bowen, James D.

AU - Boxer, Adam

AU - Burke, James R.

AU - Burns, Jeffrey M.

AU - Buxbaum, Joseph D.

AU - Cairns, Nigel J.

AU - Cantwell, Laura B.

AU - Cao, Chuanhai

AU - Carlson, Chris S.

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AU - Carroll, Steven L.

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AU - Corneveaux, Jason

AU - David, Cribbs H.

AU - Crocco, Elizabeth A.

AU - Cruchaga, Carlos

AU - De Jager, Philip L.

AU - DeCarli, Charles

AU - Yesim Demirci, F.

AU - Dick, Malcolm

AU - Dickson, Dennis W.

AU - Doody, Rachelle S.

AU - Kaye, Jeffrey

AU - Pierce, Aimee

AU - Quinn, Joseph

AU - Woltjer, Randall (Randy)

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