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
19734902
TITLE
Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease.
ABSTRACT
We undertook a two-stage genome-wide association study (GWAS) of Alzheimer's disease (AD) involving over 16,000 individuals, the most powerful AD GWAS to date. In stage 1 (3,941 cases and 7,848 controls), we replicated the established association with the apolipoprotein E (APOE) locus (most significant SNP, rs2075650, P = 1.8 x 10(-157)) and observed genome-wide significant association with SNPs at two loci not previously associated with the disease: at the CLU (also known as APOJ) gene (rs11136000, P = 1.4 x 10(-9)) and 5' to the PICALM gene (rs3851179, P = 1.9 x 10(-8)). These associations were replicated in stage 2 (2,023 cases and 2,340 controls), producing compelling evidence for association with Alzheimer's disease in the combined dataset (rs11136000, P = 8.5 x 10(-10), odds ratio = 0.86; rs3851179, P = 1.3 x 10(-9), odds ratio = 0.86).
DATE PUBLISHED
2009 Oct
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2009/04/28
accepted 2009/07/31
aheadofprint 2009/09/06
entrez 2009/09/08 06:00
pubmed 2009/09/08 06:00
medline 2009/10/15 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Harold D Harold Denise D Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff, UK.
Abraham R Abraham Richard R
Hollingworth P Hollingworth Paul P
Sims R Sims Rebecca R
Gerrish A Gerrish Amy A
Hamshere ML Hamshere Marian L ML
Pahwa JS Pahwa Jaspreet Singh JS
Moskvina V Moskvina Valentina V
Dowzell K Dowzell Kimberley K
Williams A Williams Amy A
Jones N Jones Nicola N
Thomas C Thomas Charlene C
Stretton A Stretton Alexandra A
Morgan AR Morgan Angharad R AR
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
Morgan K Morgan Kevin K
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
Love S Love Seth S
Kehoe PG Kehoe Patrick G PG
Hardy J Hardy John J
Mead S Mead Simon S
Fox N Fox Nick N
Rossor M Rossor Martin M
Collinge J Collinge John J
Maier W Maier Wolfgang W
Jessen F Jessen Frank F
Schürmann B Schürmann Britta B
Heun R Heun Reinhard R
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
Hüll M Hüll Michael M
Rujescu D Rujescu Dan D
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
Carrasquillo MM Carrasquillo Minerva M MM
Pankratz VS Pankratz V Shane VS
Younkin SG Younkin Steven G SG
Holmans PA Holmans Peter A PA
O'Donovan M O'Donovan Michael M
Owen MJ Owen Michael J MJ
Williams J Williams Julie J
INVESTIGATORS
JOURNAL
VOLUME: 41
ISSUE: 10
TITLE: Nature genetics
ISOABBREVIATION: Nat. Genet.
YEAR: 2009
MONTH: Oct
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
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
Cites Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):15233-8 10611368
Cites Nat Genet. 2009 Feb;41(2):192-8 19136949
Cites Neurology. 2001 Jan 9;56(1):127-9 11148253
Cites Biometrics. 1999 Dec;55(4):997-1004 11315092
Cites J Neurosci. 2001 Jul 1;21(13):4691-8 11425896
Cites Trends Neurosci. 2001 Nov;24(11):659-65 11672811
Cites Am J Hum Genet. 2001 Dec;69(6):1357-69 11593451
Cites Int J Biochem Cell Biol. 2002 May;34(5):427-31 11906815
Cites Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10843-8 12145324
Cites Neuron. 2004 Jan 22;41(2):193-202 14741101
Cites Trends Biochem Sci. 1992 Apr;17(4):154-9 1585460
Cites Brain Res. 1992 May 8;579(2):337-41 1378350
Cites J Biol Chem. 1993 Jan 5;268(1):608-12 8416966
Cites Biochem J. 1993 Jul 1;293 ( Pt 1):27-30 8328966
Cites J Biol Chem. 1994 Jul 1;269(26):17386-9 8021238
Cites Nature. 1994 Nov 3;372(6501):92-4 7969426
Cites Microsc Res Tech. 2000 Aug 15;50(4):305-15 10936885
Cites Am J Hum Genet. 2009 Jan;84(1):35-43 19118814
Cites Am J Hum Genet. 2008 Nov;83(5):623-32 18976728
Cites Neuron. 1999 Oct;24(2):481-9 10571241
Cites Biochem Biophys Res Commun. 1994 Dec 15;205(2):1431-7 7802679
Cites Biochem J. 1995 Mar 1;306 ( Pt 2):599-604 7534068
Cites Neurosci Lett. 1995 May 19;191(1-2):79-82 7659297
Cites Exp Neurol. 1995 Nov;136(1):22-31 7589331
Cites Proc Natl Acad Sci U S A. 1996 May 14;93(10):4804-9 8643484
Cites Proc Natl Acad Sci U S A. 1996 Apr 30;93(9):4229-34 8633046
Cites Biochem J. 1996 Jun 1;316 ( Pt 2):671-9 8687416
Cites J Neurochem. 1996 Sep;67(3):1324-7 8752142
Cites Brain Res Mol Brain Res. 1995 Oct;33(1):174-8 8774959
Cites Hum Genet. 1996 Oct;98(4):430-6 8792817
Cites Acta Neuropathol. 1998 Apr;95(4):387-94 9560017
Cites Proc Natl Acad Sci U S A. 1998 May 26;95(11):6448-53 9600986
Cites Mol Biol Cell. 1999 Aug;10(8):2687-702 10436022
Cites J Comp Neurol. 2005 Jan 3;481(1):58-69 15558718
Cites Bioinformatics. 2005 Jan 15;21(2):263-5 15297300
Cites BMC Cell Biol. 2005;6:30 16095541
Cites Nat Genet. 2005 Nov;37(11):1243-6 16228001
Cites Hum Hered. 2006;61(1):55-64 16612103
Cites Nucleic Acids Res. 2006 Jul 1;34(Web Server issue):W621-5 16845085
Cites Nat Genet. 2006 Aug;38(8):904-9 16862161
Cites J Cereb Blood Flow Metab. 2007 May;27(5):909-18 17077814
Cites Hum Mol Genet. 2007 Apr 15;16(8):865-73 17317784
Cites J Clin Psychiatry. 2007 Apr;68(4):613-8 17474819
Cites Nature. 2007 Jun 7;447(7145):661-78 17554300
Cites Neuron. 2007 Jun 7;54(5):713-20 17553421
Cites Am J Hum Genet. 2007 Sep;81(3):559-75 17701901
Cites Bioinformatics. 2007 Oct 15;23(20):2741-6 17846035
Cites Arch Neurol. 2008 Jan;65(1):45-53 17998437
Cites Traffic. 2008 Mar;9(3):417-29 18182011
Cites Neuron. 2008 Apr 10;58(1):42-51 18400162
Cites Physiol Genomics. 2008 Apr 22;33(2):240-56 18270320
Cites Nat Genet. 2008 May;40(5):638-45 18372903
Cites Am J Hum Genet. 2008 Jul;83(1):132-5; author reply 135-9 18606306
Cites Genet Epidemiol. 2008 Sep;32(6):567-73 18425821
CommentIn Nat Genet. 2009 Oct;41(10):1047-8 19786950
ErratumIn Nat Genet. 2009 Oct;41(10):1156 19786950
ErratumIn Nat Genet. 2013 Jun;45(6):712 19786950 Haun, Reinhard [added]
GRANTS
GRANTID AGENCY COUNTRY
064354 Wellcome Trust United Kingdom
082604 Wellcome Trust United Kingdom
G0300429 Medical Research Council United Kingdom
G0600974 Medical Research Council United Kingdom
G0601846 Medical Research Council United Kingdom
G0701075 Medical Research Council United Kingdom
G0900688 Medical Research Council United Kingdom
MC_U123160651 Medical Research Council United Kingdom
MC_U123192748 Medical Research Council United Kingdom
UL1 RR024992 NCRR NIH HHS United States
Intramural NIH HHS United States
Medical Research Council United Kingdom
Wellcome Trust United Kingdom
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Alzheimer Disease genetics
Chromosomes, Human genetics
Clusterin genetics
Genetic Predisposition to Disease genetics
Genome, Human genetics
Genome-Wide Association Study genetics
Humans genetics
Monomeric Clathrin Assembly Proteins genetics
Polymorphism, Single Nucleotide genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 CLU protein, human
0 Clusterin
0 Monomeric Clathrin Assembly Proteins
0 PICALM protein, human
OTHER ID's
OTHERID SOURCE
PMC2845877 NLM
UKMS27833 NLM
Designed by: GenEpi IT
Maintained by: GenEpi IT
Feedback: webmaster
Copyright © 2007 QIMR
For more information Contact Us
epiit@qimr.edu.au
Last Modified: Oct 15 2007