Association of Alzheimer's disease GWAS loci with MRI markers of brain aging

被引：69

作者：

Chauhan, Ganesh ^{[1
,2
]}

Adams, Hieab H. H. ^{[3
,4
]}

Bis, Joshua C. ^{[5
]}

Weinstein, Galit ^{[6
,7
]}

Yu, Lei ^{[8
,9
]}

Toglhofer, Anna Maria ^{[10
]}

Smith, Albert Vernon ^{[11
,12
]}

van der Lee, Sven J. ^{[3
]}

Gottesmanm, Rebecca F. ^{[13
,14
]}

Thomson, Russell ^{[15
]}

Wang, Jing ^{[7
,16
]}

Yang, Qiong ^{[7
,16
]}

Niessen, Wiro J. ^{[4
]}

Lopez, Oscar L. ^{[17
,18
]}

Becker, James T. ^{[17
,18
,19
]}

Phan, Thanh G. ^{[20
]}

Beare, Richard J. ^{[20
,21
]}

Arfanakis, Konstantinos ^{[8
,22
]}

Fleischman, Debra ^{[8
]}

Vernooij, Meike W. ^{[3
,4
]}

Mazoyer, Bernard ^{[23
]}

Schmidt, Helena ^{[10
]}

Srikanth, Velandai ^{[15
,20
]}

Knopman, David S. ^{[24
]}

Jack, Clifford R., Jr. ^{[25
]}

Amouyel, Philippe ^{[26
,27
,28
]}

Hofman, Albert ^{[3
]}

DeCarli, Charles ^{[29
]}

Tzourio, Christophe ^{[1
]}

van Duijnc, Cornelia M. ^{[3
,30
,31
]}

Bennett, David A. ^{[8
,9
]}

Schmidt, Reinhold ^{[32
]}

Longstreth, William T., Jr. ^{[33
]}

Mosley, Thomas H. ^{[34
]}

Fornage, Myriam ^{[35
,36
]}

Launer, Lenore J. ^{[37
]}

Seshadri, Sudha ^{[6
,7
]}

Ikramc, M. Arfan ^{[3
,4
,30
]}

Debette, Stephanie ^{[1
,2
,6
,38
]}

机构：

[1] Univ Bordeaux, INSERM U897, F-33076 Bordeaux, France

[2] Univ Bordeaux, F-33076 Bordeaux, France

[3] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands

[4] Erasmus MC, Dept Radiol, Rotterdam, Netherlands

[5] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA

[6] Boston Univ, Dept Neurol, Sch Med, Boston, MA 02215 USA

[7] Framingham Heart Dis Epidemiol Study, Boston, MA USA

[8] Rush Univ, Rush Alzheimers Dis Ctr, Med Ctr, Chicago, IL 60612 USA

[9] Rush Univ, Dept Neurol Sci, Med Ctr, Chicago, IL 60612 USA

[10] Med Univ Graz, Ctr Mol Med, Inst Mol Biol & Biochem, Graz, Austria

[11] Iceland Heart Assoc, Reykjavik, Iceland

[12] Univ Iceland, Dept Med, Reykjavik, Iceland

[13] Johns Hopkins Sch Med, Dept Neurol, Baltimore, MD USA

[14] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA

[15] Univ Tasmania, Menzies Res Inst Tasmania, Hobart, Tas, Australia

[16] Boston Univ, Dept Biostat, Sch Publ Hlth, Boston, MA 02215 USA

[17] Univ Pittsburgh, Dept Neurol, Sch Med, Pittsburgh, PA 15260 USA

[18] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA

[19] Univ Pittsburgh, Dept Psychol, Sch Med, Pittsburgh, PA 15260 USA

[20] Monash Univ, Dept Med, Southern Clin Sch, Stroke & Ageing Res Ctr, Melbourne, Vic 3004, Australia

[21] Royal Childrens Hosp, Murdoch Childrens Res Inst, Dev Imaging Grp, Parkville, Vic 3052, Australia

[22] Illinois Inst Technol, Dept Biomed Engn, Chicago, IL USA

[23] Univ Bordeaux, Grp Imagerie Neurofonctionnelle, UMR5296, CNRS,CEA, Bordeaux, France

[24] Mayo Clin, Dept Neurol, Coll Med, Rochester, MN USA

[25] Mayo Clin, Dept Radiol, Coll Med, Rochester, MN USA

[26] Inst Pasteur, Dept Epidemiol & Publ Hlth, F-59019 Lille, France

[27] INSERM, U744, F-59045 Lille, France

[28] Univ Lille 2, Lille, France

[29] Univ Calif Davis, Dept Neurol, Davis, CA 95616 USA

[30] Netherlands Consortium Hlth Aging, Leiden, Netherlands

[31] Ctr Med Syst Biol, Leiden, Netherlands

[32] Med Univ Graz, Dept Neurol Clin Div Neurogeriatr, Graz, Austria

[33] Univ Washington, Dept Neurol & Epidemiol, Seattle, WA 98195 USA

[34] Univ Mississippi, Dept Med Geriatr Gerontol, Med Ctr, Jackson, MS 39216 USA

[35] Univ Texas Houston, Ctr Human Genet, Hlth Sci Ctr, Houston, TX USA

[36] Univ Texas Houston, Inst Mol Med, Hlth Sci Ctr, Houston, TX USA

[37] NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, Natl Inst Hlth, Bethesda, MD 20892 USA

[38] Bordeaux Univ Hosp, Dept Neurol, Bordeaux, France

来源：

NEUROBIOLOGY OF AGING | 2015年 / 36卷 / 04期

基金：

英国医学研究理事会; 美国国家卫生研究院; 奥地利科学基金会; 澳大利亚国家健康与医学研究理事会;

关键词：

Alzheimer; MRI-Markers; Genetic risk score; GWAS; Hippocampal volume; GENOME-WIDE ASSOCIATION; APOLIPOPROTEIN-E EPSILON-4; SAMPLE-SIZE REQUIREMENTS; HIPPOCAMPAL VOLUME; COMMON VARIANTS; IDENTIFIES VARIANTS; GENETIC-VARIATION; ATROPHY; CD33; APOE;

D O I：

10.1016/j.neurobiolaging.2014.12.028

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：

Whether novel risk variants of Alzheimer's disease (AD) identified through genome-wide association studies also influence magnetic resonance imaging-based intermediate phenotypes of AD in the general population is unclear. We studied association of 24 AD risk loci with intracranial volume, total brain volume, hippocampal volume (HV), white matter hyperintensity burden, and brain infarcts in a meta-analysis of genetic association studies from large population-based samples (N = 8175-11,550). In single-SNP based tests, AD risk allele of APOE (rs2075650) was associated with smaller HV (p = 0.0054) and CD33 (rs3865444) with smaller intracranial volume (p = 0.0058). In gene-based tests, there was associations of HLA-DRB1 with total brain volume (p = 0.0006) and BIN1 with HV (p = 0.00089). A weighted AD genetic risk score was associated with smaller HV (beta +/- SE = -0.047 +/- 0.013, p = 0.00041), even after excluding the APOE locus (p = 0.029). However, only association of AD genetic risk score with HV, including APOE, was significant after multiple testing correction (including number of independent phenotypes tested). These results suggest that novel AD genetic risk variants may contribute to structural brain aging in nondemented older community persons. (C) 2015 Elsevier Inc. All rights reserved.

引用

页码：1765.e7 / 1765.e16

页数：10

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