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.
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PMID
21085570
TITLE
Genetic evidence implicates the immune system and cholesterol metabolism in the aetiology of Alzheimer's disease.
ABSTRACT
BACKGROUND NlmCategory: BACKGROUND
Late Onset Alzheimer's disease (LOAD) is the leading cause of dementia. Recent large genome-wide association studies (GWAS) identified the first strongly supported LOAD susceptibility genes since the discovery of the involvement of APOE in the early 1990s. We have now exploited these GWAS datasets to uncover key LOAD pathophysiological processes.
METHODOLOGY NlmCategory: METHODS
We applied a recently developed tool for mining GWAS data for biologically meaningful information to a LOAD GWAS dataset. The principal findings were then tested in an independent GWAS dataset.
PRINCIPAL FINDINGS NlmCategory: RESULTS
We found a significant overrepresentation of association signals in pathways related to cholesterol metabolism and the immune response in both of the two largest genome-wide association studies for LOAD.
SIGNIFICANCE NlmCategory: CONCLUSIONS
Processes related to cholesterol metabolism and the innate immune response have previously been implicated by pathological and epidemiological studies of Alzheimer's disease, but it has been unclear whether those findings reflected primary aetiological events or consequences of the disease process. Our independent evidence from two large studies now demonstrates that these processes are aetiologically relevant, and suggests that they may be suitable targets for novel and existing therapeutic approaches.
DATE PUBLISHED
2010
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2010/06/23
accepted 2010/10/06
epublish 2010/11/15
entrez 2010/11/19 06:00
pubmed 2010/11/19 06:00
medline 2011/04/28 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Jones L Jones Lesley L Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Cardiff, United Kingdom.
Holmans PA Holmans Peter A PA
Hamshere ML Hamshere Marian L ML
Harold D Harold Denise D
Moskvina V Moskvina Valentina V
Ivanov D Ivanov Dobril D
Pocklington A Pocklington Andrew A
Abraham R Abraham Richard R
Hollingworth P Hollingworth Paul P
Sims R Sims Rebecca R
Gerrish A Gerrish Amy A
Pahwa JS Pahwa Jaspreet Singh JS
Jones N Jones Nicola N
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
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
Kölsch H Kölsch Heike H
van den Bussche H van den Bussche Hendrik H
Heuser I Heuser Isabella I
Peters O Peters Oliver O
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
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 Panos P
Al-Chalabi A Al-Chalabi Ammar A
Shaw CE Shaw Christopher E CE
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
Rüther E Rüther Eckhard E
Carrasquillo MM Carrasquillo Minerva M MM
Pankratz VS Pankratz V Shane VS
Younkin SG Younkin Steven G SG
Hardy J Hardy John J
O'Donovan MC O'Donovan Michael C MC
Owen MJ Owen Michael J MJ
Williams J Williams Julie J
INVESTIGATORS
JOURNAL
VOLUME: 5
ISSUE: 11
TITLE: PloS one
ISOABBREVIATION: PLoS ONE
YEAR: 2010
MONTH:
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1932-6203
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: PLoS One
COUNTRY: United States
ISSNLINKING: 1932-6203
NLMUNIQUEID: 101285081
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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ErratumIn PLoS One. 2011;6(2). doi:10.1371/annotation/a0bb886d-d345-4a20-a82e-adce9b047798 8346443 Heun, Reinhard [added]; Kölsch, Heike [added]
GRANTS
GRANTID AGENCY COUNTRY
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
Z01 AG000950-06 NIA NIH HHS United States
Medical Research Council United Kingdom
Wellcome Trust United Kingdom
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Alzheimer Disease metabolism
Apolipoproteins E metabolism
Cholesterol metabolism
Chromosome Mapping metabolism
Genetic Predisposition to Disease genetics
Genome, Human genetics
Genome-Wide Association Study genetics
Humans genetics
Immune System metabolism
Polymorphism, Single Nucleotide metabolism
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Apolipoproteins E
97C5T2UQ7J Cholesterol
OTHER ID's
OTHERID SOURCE
PMC2981526 NLM