Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
QIMR Home Page
GenEpi Home Page
About GenEpi
Publications
Contacts
Research
Staff Index
Collaborators
Software Tools
Computing Resources
Studies
Search
GenEpi Intranet
PMID
21460840
TITLE
Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease.
ABSTRACT
We sought to identify new susceptibility loci for Alzheimer's disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer's Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P ≤ 1 × 10(-5). We tested these variants for association in an independent sample (stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (stage 3). Meta-analyses of all data provided compelling evidence that ABCA7 (rs3764650, meta P = 4.5 × 10(-17); including ADGC data, meta P = 5.0 × 10(-21)) and the MS4A gene cluster (rs610932, meta P = 1.8 × 10(-14); including ADGC data, meta P = 1.2 × 10(-16)) are new Alzheimer's disease susceptibility loci. We also found independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance: CD2AP (GERAD+, P = 8.0 × 10(-4); including ADGC data, meta P = 8.6 × 10(-9)), CD33 (GERAD+, P = 2.2 × 10(-4); including ADGC data, meta P = 1.6 × 10(-9)) and EPHA1 (GERAD+, P = 3.4 × 10(-4); including ADGC data, meta P = 6.0 × 10(-10)).
DATE PUBLISHED
2011 May
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2010/09/09
accepted 2011/03/10
aheadofprint 2011/04/03
entrez 2011/04/05 06:00
pubmed 2011/04/05 06:00
medline 2011/07/02 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Hollingworth P Hollingworth Paul P Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Neurosciences and Mental Health Research Institute, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff, UK.
Harold D Harold Denise D
Sims R Sims Rebecca R
Gerrish A Gerrish Amy A
Lambert JC Lambert Jean-Charles JC
Carrasquillo MM Carrasquillo Minerva M MM
Abraham R Abraham Richard R
Hamshere ML Hamshere Marian L ML
Pahwa JS Pahwa Jaspreet Singh JS
Moskvina V Moskvina Valentina V
Dowzell K Dowzell Kimberley K
Jones N Jones Nicola N
Stretton A Stretton Alexandra A
Thomas C Thomas Charlene C
Richards A Richards Alex A
Ivanov D Ivanov Dobril D
Widdowson C Widdowson Caroline C
Chapman J Chapman Jade J
Lovestone S Lovestone Simon S
Powell J Powell John J
Proitsi P Proitsi Petroula P
Lupton MK Lupton Michelle K MK
Brayne C Brayne Carol C
Rubinsztein DC Rubinsztein David C DC
Gill M Gill Michael M
Lawlor B Lawlor Brian B
Lynch A Lynch Aoibhinn A
Brown KS Brown Kristelle S KS
Passmore PA Passmore Peter A PA
Craig D Craig David D
McGuinness B McGuinness Bernadette B
Todd S Todd Stephen S
Holmes C Holmes Clive C
Mann D Mann David D
Smith AD Smith A David AD
Beaumont H Beaumont Helen H
Warden D Warden Donald D
Wilcock G Wilcock Gordon G
Love S Love Seth S
Kehoe PG Kehoe Patrick G PG
Hooper NM Hooper Nigel M NM
Vardy ER Vardy Emma R L C ER
Hardy J Hardy John J
Mead S Mead Simon S
Fox NC Fox Nick C NC
Rossor M Rossor Martin M
Collinge J Collinge John J
Maier W Maier Wolfgang W
Jessen F Jessen Frank F
Rüther E Rüther Eckart E
Schürmann B Schürmann Britta B
Heun R Heun Reiner R
Kölsch H Kölsch Heike H
van den Bussche H van den Bussche Hendrik H
Heuser I Heuser Isabella I
Kornhuber J Kornhuber Johannes J
Wiltfang J Wiltfang Jens J
Dichgans M Dichgans Martin M
Frölich L Frölich Lutz L
Hampel H Hampel Harald H
Gallacher J Gallacher John J
Hüll M Hüll Michael M
Rujescu D Rujescu Dan D
Giegling I Giegling Ina I
Goate AM Goate Alison M AM
Kauwe JS Kauwe John S K JS
Cruchaga C Cruchaga Carlos C
Nowotny P Nowotny Petra P
Morris JC Morris John C JC
Mayo K Mayo Kevin K
Sleegers K Sleegers Kristel K
Bettens K Bettens Karolien K
Engelborghs S Engelborghs Sebastiaan S
De Deyn PP De Deyn Peter P PP
Van Broeckhoven C Van Broeckhoven Christine C
Livingston G Livingston Gill G
Bass NJ Bass Nicholas J NJ
Gurling H Gurling Hugh H
McQuillin A McQuillin Andrew A
Gwilliam R Gwilliam Rhian R
Deloukas P Deloukas Panagiotis P
Al-Chalabi A Al-Chalabi Ammar A
Shaw CE Shaw Christopher E CE
Tsolaki M Tsolaki Magda M
Singleton AB Singleton Andrew B AB
Guerreiro R Guerreiro Rita R
Mühleisen TW Mühleisen Thomas W TW
Nöthen MM Nöthen Markus M MM
Moebus S Moebus Susanne S
Jöckel KH Jöckel Karl-Heinz KH
Klopp N Klopp Norman N
Wichmann HE Wichmann H-Erich HE
Pankratz VS Pankratz V Shane VS
Sando SB Sando Sigrid B SB
Aasly JO Aasly Jan O JO
Barcikowska M Barcikowska Maria M
Wszolek ZK Wszolek Zbigniew K ZK
Dickson DW Dickson Dennis W DW
Graff-Radford NR Graff-Radford Neill R NR
Petersen RC Petersen Ronald C RC
Alzheimer's Disease Neuroimaging Initiative
van Duijn CM van Duijn Cornelia M CM
Breteler MM Breteler Monique M B MM
Ikram MA Ikram M Arfan MA
DeStefano AL DeStefano Anita L AL
Fitzpatrick AL Fitzpatrick Annette L AL
Lopez O Lopez Oscar O
Launer LJ Launer Lenore J LJ
Seshadri S Seshadri Sudha S
CHARGE consortium
Berr C Berr Claudine C
Campion D Campion Dominique D
Epelbaum J Epelbaum Jacques J
Dartigues JF Dartigues Jean-François JF
Tzourio C Tzourio Christophe C
Alpérovitch A Alpérovitch Annick A
Lathrop M Lathrop Mark M
EADI1 consortium
Feulner TM Feulner Thomas M TM
Friedrich P Friedrich Patricia P
Riehle C Riehle Caterina C
Krawczak M Krawczak Michael M
Schreiber S Schreiber Stefan S
Mayhaus M Mayhaus Manuel M
Nicolhaus S Nicolhaus S S
Wagenpfeil S Wagenpfeil Stefan S
Steinberg S Steinberg Stacy S
Stefansson H Stefansson Hreinn H
Stefansson K Stefansson Kari K
Snaedal J Snaedal Jon J
Björnsson S Björnsson Sigurbjörn S
Jonsson PV Jonsson Palmi V PV
Chouraki V Chouraki Vincent V
Genier-Boley B Genier-Boley Benjamin B
Hiltunen M Hiltunen Mikko M
Soininen H Soininen Hilkka H
Combarros O Combarros Onofre O
Zelenika D Zelenika Diana D
Delepine M Delepine Marc M
Bullido MJ Bullido Maria J MJ
Pasquier F Pasquier Florence F
Mateo I Mateo Ignacio I
Frank-Garcia A Frank-Garcia Ana A
Porcellini E Porcellini Elisa E
Hanon O Hanon Olivier O
Coto E Coto Eliecer E
Alvarez V Alvarez Victoria V
Bosco P Bosco Paolo P
Siciliano G Siciliano Gabriele G
Mancuso M Mancuso Michelangelo M
Panza F Panza Francesco F
Solfrizzi V Solfrizzi Vincenzo V
Nacmias B Nacmias Benedetta B
Sorbi S Sorbi Sandro S
Bossù P Bossù Paola P
Piccardi P Piccardi Paola P
Arosio B Arosio Beatrice B
Annoni G Annoni Giorgio G
Seripa D Seripa Davide D
Pilotto A Pilotto Alberto A
Scarpini E Scarpini Elio E
Galimberti D Galimberti Daniela D
Brice A Brice Alexis A
Hannequin D Hannequin Didier D
Licastro F Licastro Federico F
Jones L Jones Lesley L
Holmans PA Holmans Peter A PA
Jonsson T Jonsson Thorlakur T
Riemenschneider M Riemenschneider Matthias M
Morgan K Morgan Kevin K
Younkin SG Younkin Steven G SG
Owen MJ Owen Michael J MJ
O'Donovan M O'Donovan Michael M
Amouyel P Amouyel Philippe P
Williams J Williams Julie J
INVESTIGATORS
JOURNAL
VOLUME: 43
ISSUE: 5
TITLE: Nature genetics
ISOABBREVIATION: Nat. Genet.
YEAR: 2011
MONTH: May
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1546-1718
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Nat Genet
COUNTRY: United States
ISSNLINKING: 1061-4036
NLMUNIQUEID: 9216904
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
Cites Neuron. 2007 Jun 7;54(5):713-20 17553421
Cites Neurobiol Aging. 2012 Mar;33(3):518-21 20570404
Cites Nat Genet. 2007 Dec;39(12):1494-9 17982457
Cites Immunogenetics. 2001 Jul;53(5):357-68 11486273
Cites Growth Factors. 2001;18(4):303-17 11519828
Cites J Biol Chem. 2003 Jun 13;278(24):21805-13 12672817
Cites Neurology. 1984 Jul;34(7):939-44 6610841
Cites Proc Natl Acad Sci U S A. 1988 Sep;85(17):6483-7 2970642
Cites Neurology. 1991 Apr;41(4):479-86 2011243
Cites Neurology. 1993 Aug;43(8):1467-72 8350998
Cites Cell. 1998 Sep 4;94(5):667-77 9741631
Cites J Biol Chem. 2005 Feb 4;280(5):3989-95 15550377
Cites Brain Res Brain Res Rev. 2005 Sep;49(2):211-26 16111551
Cites Arch Gen Psychiatry. 2006 Feb;63(2):168-74 16461860
Cites Neuroreport. 2006 Jun 26;17(9):891-6 16738483
Cites PLoS Genet. 2005 Dec;1(6):e78 16362079
Cites IUBMB Life. 2006 Jul;58(7):389-94 16801213
Cites J Cell Biol. 2006 Aug 14;174(4):547-56 16908670
Cites Nat Rev Immunol. 2007 Apr;7(4):255-66 17380156
Cites J Neurochem. 2008 Mar;104(5):1145-66 17973979
Cites Genet Epidemiol. 2008 May;32(4):381-5 18348202
Cites Genesis. 2008 Oct;46(10):553-61 18802966
Cites Am J Hum Genet. 2008 Nov;83(5):623-32 18976728
Cites J Cell Sci. 2009 Jan 15;122(Pt 2):243-55 19118217
Cites Curr Opin Neurobiol. 2009 Jun;19(3):275-83 19497733
Cites Nat Genet. 2009 Oct;41(10):1088-93 19734902
Cites Nat Genet. 2009 Oct;41(10):1094-9 19734903
Cites Neurology. 2010 Jan 19;74(3):201-9 20042704
Cites Nat Methods. 2010 Apr;7(4):248-9 20354512
Cites JAMA. 2010 May 12;303(18):1832-40 20460622
Cites PLoS Genet. 2010 May;6(5):e1000952 20485568
Cites Arch Neurol. 2010 Jun;67(6):677-85 20558387
Cites Hum Mol Genet. 2010 Aug 15;19(16):3295-301 20534741
Cites Brain Res. 2010 Aug 12;1348:216-21 20558149
Cites Arch Neurol. 2010 Aug;67(8):961-4 20554627
Cites Arch Neurol. 2010 Dec;67(12):1473-84 20697030
Cites Nat Genet. 2011 May;43(5):436-41 21460841
Cites Mol Cell Biol. 2007 Aug;27(16):5699-710 17562860
GRANTS
GRANTID AGENCY COUNTRY
082604 Wellcome Trust United Kingdom
G0300429 Medical Research Council United Kingdom
G0601846 Medical Research Council United Kingdom
G0701075 Medical Research Council United Kingdom
G0802189 Medical Research Council United Kingdom
G0900688 Medical Research Council United Kingdom
G0902227 Medical Research Council United Kingdom
G9810900 Medical Research Council United Kingdom
MC_G1000734 Medical Research Council United Kingdom
MC_U123160651 Medical Research Council United Kingdom
U24 AG021886 NIA NIH HHS United States
Medical Research Council United Kingdom
Wellcome Trust United Kingdom
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
ATP-Binding Cassette Transporters genetics
Adaptor Proteins, Signal Transducing genetics
Aged genetics
Aged, 80 and over genetics
Alzheimer Disease genetics
Antigens, CD genetics
Antigens, Differentiation, Myelomonocytic genetics
Case-Control Studies genetics
Cytoskeletal Proteins genetics
Databases, Genetic genetics
Female genetics
Genetic Predisposition to Disease genetics
Genetic Variation genetics
Genome-Wide Association Study genetics
Humans genetics
Male genetics
Membrane Proteins genetics
Multigene Family genetics
Polymorphism, Single Nucleotide genetics
Receptor, EphA1 genetics
Sialic Acid Binding Ig-like Lectin 3 genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 ABCA7 protein, human
0 Adaptor Proteins, Signal Transducing
0 Antigens, CD
0 Antigens, Differentiation, Myelomonocytic
0 CD2-associated protein
0 CD33 protein, human
0 Cytoskeletal Proteins
0 MS4A4E protein, human
0 Membrane Proteins
0 Sialic Acid Binding Ig-like Lectin 3
EC 2.7.10.1 Receptor, EphA1
OTHER ID's
OTHERID SOURCE
PMC3084173 NLM
UKMS34702 NLM