Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease

被引：1473

作者：

Naj, Adam C. ^{[2
]}

Jun, Gyungah ^{[3
,4
,5
]}

Beecham, Gary W. ^{[2
]}

Wang, Li-San ^{[1
]}

Vardarajan, Badri Narayan ^{[4
]}

Buros, Jacqueline ^{[4
]}

Gallins, Paul J. ^{[2
]}

Buxbaum, Joseph D. ^{[7
,8
,9
]}

Jarvik, Gail P. ^{[10
,11
]}

Crane, Paul K. ^{[12
]}

Larson, Eric B. ^{[13
]}

Bird, Thomas D. ^{[14
]}

Boeve, Bradley F. ^{[15
]}

Graff-Radford, Neill R. ^{[16
,17
]}

De Jager, Philip L. ^{[18
,19
]}

Evans, Denis ^{[20
]}

Schneider, Julie A. ^{[21
,22
]}

Carrasquillo, Minerva M. ^{[16
]}

Ertekin-Taner, Nilufer ^{[16
,17
]}

Younkin, Steven G. ^{[16
]}

Cruchaga, Carlos ^{[23
,24
]}

Kauwe, John S. K. ^{[25
]}

Nowotny, Petra ^{[23
,24
]}

Kramer, Patricia ^{[26
,27
]}

Hardy, John ^{[28
]}

Huentelman, Matthew J. ^{[29
]}

Myers, Amanda J. ^{[30
]}

Barmada, Michael M. ^{[31
]}

Demirci, F. Yesim ^{[31
]}

Baldwin, Clinton T. ^{[4
]}

Green, Robert C. ^{[4
,32
,33
]}

Rogaeva, Ekaterina ^{[34
]}

St George-Hyslop, Peter ^{[34
,35
,115
]}

Arnold, Steven E. ^{[36
]}

Barber, Robert ^{[37
]}

Beach, Thomas ^{[38
]}

Bigio, Eileen H. ^{[39
]}

Bowen, James D. ^{[40
]}

Boxer, Adam ^{[41
]}

Burke, James R. ^{[42
]}

Cairns, Nigel J. ^{[43
]}

Carlson, Chris S. ^{[44
]}

Carney, Regina M. ^{[45
]}

Carroll, Steven L. ^{[46
]}

Chui, Helena C. ^{[47
]}

Clark, David G. ^{[48
]}

Corneveaux, Jason ^{[29
]}

Cotman, Carl W. ^{[49
]}

Cummings, Jeffrey L. ^{[50
]}

DeCarli, Charles ^{[51
]}

机构：

[1] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA

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

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

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

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

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

[7] Mt Sinai Sch Med, Dept Neurosci, New York, NY USA

[8] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA

[9] Mt Sinai Sch Med, Dept Genet & Genom Sci, Sch Med, New York, NY USA

[10] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA

[11] Univ Washington, Dept Med Med Genet, Seattle, WA 98195 USA

[12] Univ Washington, Dept Med, Seattle, WA 98195 USA

[13] Res Inst, Grp Hlth, Seattle, WA USA

[14] Univ Washington, Dept Neurol, Seattle, WA 98195 USA

[15] Mayo Clin, Dept Neurol, Rochester, MN USA

[16] Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA

[17] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA

[18] Brigham & Womens Hosp, Program Translat NeuroPsychiat Genom, Dept Neurol, Boston, MA 02115 USA

[19] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA

[20] Rush Univ, Med Ctr, Rush Inst Healthy Aging, Dept Internal Med, Chicago, IL 60612 USA

[21] Rush Univ, Med Ctr, Dept Pathol Neuropathol, Chicago, IL 60612 USA

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

[23] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA

[24] Washington Univ, Sch Med, Hope Ctr Program Prot Aggregat & Neurodegenerat, St Louis, MO 63110 USA

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

[26] Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Portland, OR 97201 USA

[27] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA

[28] UCL, Dept Neurol, London, England

[29] Translat Genom Res Inst, Neurogenom Div, Phoenix, AZ USA

[30] Univ Miami, Dept Psychiat & Behav Sci, Miami, FL USA

[31] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA

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

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

[34] Univ Toronto, Tanz Ctr Res Neurodegenerat Dis, Toronto, ON, Canada

[35] Univ Cambridge, Dept Clin Neurosci, Cambridge, Massachusetts, England

[36] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA

[37] Univ Texas SW, Dept Pharmacol & Neurosci, Ft Worth, TX USA

[38] Banner Sun Hlth Res Inst, Civin Lab Neuropathol, Phoenix, AZ USA

[39] Northwestern Univ, Dept Pathol, Chicago, IL 60611 USA

[40] Swedish Med Ctr, Seattle, WA USA

[41] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA

[42] Duke Univ, Dept Med, Durham, NC USA

[43] Washington Univ, Dept Pathol & Immunol, St Louis, MO USA

[44] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA

[45] Vanderbilt Univ, Dept Psychiat, Nashville, TN USA

[46] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA

[47] Univ So Calif, Dept Neurol, Los Angeles, CA USA

[48] Univ Alabama Birmingham, Dept Neurol, Birmingham, AL 35294 USA

[49] Univ Calif Irvine, Inst Memory Impairments & Neurol Disorders, Irvine, CA USA

[50] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA

来源：

NATURE GENETICS | 2011年 / 43卷 / 05期

基金：

英国惠康基金; 美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; IDENTIFIES VARIANTS; MISSENSE MUTATIONS; GENE; POPULATION; METAANALYSIS; LOCI; CLU; SUSCEPTIBILITY; EFFICIENT;

D O I：

10.1038/ng.801

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

The Alzheimer Disease Genetics Consortium (ADGC) performed a genome-wide association study of late-onset Alzheimer disease using a three-stage design consisting of a discovery stage (stage 1) and two replication stages (stages 2 and 3). Both joint analysis and meta-analysis approaches were used. We obtained genome-wide significant results at MS4A4A (rs4938933; stages 1 and 2, meta-analysis P (P-M) = 1.7 x 10(-9), joint analysis P (P-J) = 1.7 x 10(-9); stages 1, 2 and 3, P-M = 8.2 x 10(-12)), CD2AP (rs9349407; stages 1, 2 and 3, P-M = 8.6 x 10(-9)), EPHA1 (rs11767557; stages 1, 2 and 3, P-M = 6.0 x 10(-10)) and CD33 (rs3865444; stages 1, 2 and 3, P-M = 1.6 x 10(-9)). We also replicated previous associations at CR1 (rs6701713; P-M = 4.6 x 10(-10), P-J = 5.2 x 10(-11)), CLU (rs1532278; P-M = 8.3 x 10(-8), P-J = 1.9 x 10(-8)), BIN1 (rs7561528; P-M = 4.0 x 10(-14), P-J = 5.2 x 10(-14)) and PICALM (rs561655; P-M = 7.0 x 10(-11), P-J = 1.0 x 10(-10)), but not at EXOC3L2, to late-onset Alzheimer's disease susceptibility(1-3).

引用

页码：436 / +

页数：8

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