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

被引：175

作者：

Ridge, Perry G. ^{[1
]}

Hoyt, Kaitlyn B. ^{[1
]}

Boehme, Kevin ^{[1
]}

Mukherjee, Shubhabrata ^{[2
]}

Crane, Paul K. ^{[2
]}

Haines, Jonathan L. ^{[3
]}

Mayeux, Richard ^{[4
,5
]}

Farrer, Lindsay A. ^{[6
,7
,8
,9
,10
]}

Pericak-Vance, Margaret A. ^{[11
,12
]}

Schellenberg, Gerard D. ^{[13
]}

Kauwe, John S. K. ^{[1
]}

机构：

[1] Brigham Young Univ, Dept Biol, Provo, UT 84602 USA

[2] Univ Washington, Dept Med, Seattle, WA USA

[3] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA

[4] Columbia Univ, Dept Neurol, New York, NY USA

[5] Columbia Univ, Gertrude H Sergievsky Ctr, Taub Inst Alzheimers Dis & Aging Brain, New York, NY 10027 USA

[6] Boston Univ, Dept Biostat, Boston, MA 02215 USA

[7] Boston Univ, Dept Epidemiol, Boston, MA 02215 USA

[8] Boston Univ, Dept Med, Genet Program, Boston, MA 02215 USA

[9] Boston Univ, Dept Neurol, Boston, MA 02215 USA

[10] Boston Univ, Dept Ophthalmol, Boston, MA 02215 USA

[11] Univ Miami, Dr John T Macdonald Fdn, Dept Human Genet, Miami, FL USA

[12] Univ Miami, John P Hussman Inst Human Genom, Miami, FL USA

[13] Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA USA

来源：

NEUROBIOLOGY OF AGING | 2016年 / 41卷

基金：

英国惠康基金; 加拿大健康研究院; 美国国家卫生研究院; 英国医学研究理事会;

关键词：

Alzheimer's disease; Genetics; Genetic variance; COMMON VARIANTS; ASSOCIATION; MUTATION; LINKAGE; ALLELE; CD2AP; EPHA1; CD33; CR-1; CLU;

D O I：

10.1016/j.neurobiolaging.2016.02.024

中图分类号：

R592 [老年病学]; C [社会科学总论];

学科分类号：

03 ; 0303 ; 100203 ;

摘要：

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. (C) 2016 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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