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

doi:10.1016/j.neurobiolaging.2016.02.024

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

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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 language	English
Pages (from-to)	200.e13-200.e20
Journal	Neurobiology of Aging
Volume	41
DOIs	https://doi.org/10.1016/j.neurobiolaging.2016.02.024
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

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10.1016/j.neurobiolaging.2016.02.024

Cite this

@article{62eca78282ed45a3adeaf443dd4778ae,

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.",

keywords = "Alzheimer's disease, Genetic variance, Genetics",

author = "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 Ranjan Duara and Fardo, \{David W.\} and Jicha, \{Gregory A.\} and \{Van Eldik\}, \{Linda J.\}",

note = "Publisher Copyright: {\textcopyright} 2016 The Authors.",

year = "2016",

month = may,

day = "1",

doi = "10.1016/j.neurobiolaging.2016.02.024",

language = "English",

volume = "41",

pages = "200.e13--200.e20",

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AU - Adams, Perrie M.

AU - Albert, Marilyn S.

AU - Albin, Roger L.

AU - Apostolova, Liana G.

AU - Arnold, Steven E.

AU - Asthana, Sanjay

AU - Atwood, Craig S.

AU - Baldwin, Clinton T.

AU - Barber, Robert C.

AU - Barmada, Michael M.

AU - Barnes, Lisa L.

AU - Barral, Sandra

AU - Beach, Thomas G.

AU - Becker, James T.

AU - Beecham, Gary W.

AU - Beekly, Duane

AU - Bennett, David A.

AU - Bigio, Eileen H.

AU - Bird, Thomas D.

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.

AU - Carlsson, Cynthia M.

AU - Carney, Regina M.

AU - Carrasquillo, Minerva M.

AU - Carroll, Steven L.

AU - Chui, Helena C.

AU - Clark, David G.

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 - Duara, Ranjan

AU - Fardo, David W.

AU - Jicha, Gregory A.

AU - Van Eldik, Linda J.

PY - 2016/5/1

Y1 - 2016/5/1

N2 - 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.

AB - 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.

KW - Alzheimer's disease

KW - Genetic variance

KW - Genetics

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AN - SCOPUS:84962300984

SN - 0197-4580

VL - 41

SP - 200.e13-200.e20

JO - Neurobiology of Aging

JF - Neurobiology of Aging

ER -

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

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

Access to Document

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