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
22027014
TITLE
The role of variation at AßPP, PSEN1, PSEN2, and MAPT in late onset Alzheimer's disease.
ABSTRACT
Rare mutations in AβPP, PSEN1, and PSEN2 cause uncommon early onset forms of Alzheimer's disease (AD), and common variants in MAPT are associated with risk of other neurodegenerative disorders. We sought to establish whether common genetic variation in these genes confer risk to the common form of AD which occurs later in life (>65 years). We therefore tested single-nucleotide polymorphisms at these loci for association with late-onset AD (LOAD) in a large case-control sample consisting of 3,940 cases and 13,373 controls. Single-marker analysis did not identify any variants that reached genome-wide significance, a result which is supported by other recent genome-wide association studies. However, we did observe a significant association at the MAPT locus using a gene-wide approach (p = 0.009). We also observed suggestive association between AD and the marker rs9468, which defines the H1 haplotype, an extended haplotype that spans the MAPT gene and has previously been implicated in other neurodegenerative disorders including Parkinson's disease, progressive supranuclear palsy, and corticobasal degeneration. In summary common variants at AβPP, PSEN1, and PSEN2 and MAPT are unlikely to make strong contributions to susceptibility for LOAD. However, the gene-wide effect observed at MAPT indicates a possible contribution to disease risk which requires further study.
DATE PUBLISHED
2012
HISTORY
PUBSTATUS PUBSTATUSDATE
entrez 2011/10/27 06:00
pubmed 2011/10/27 06:00
medline 2012/05/25 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Gerrish A Gerrish Amy A MRC Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, UK.
Russo G Russo Giancarlo G
Richards A Richards Alexander A
Moskvina V Moskvina Valentina V
Ivanov D Ivanov Dobril D
Harold D Harold Denise D
Sims R Sims Rebecca R
Abraham R Abraham Richard R
Hollingworth P Hollingworth Paul P
Chapman J Chapman Jade J
Hamshere M Hamshere Marian M
Pahwa JS Pahwa Jaspreet Singh JS
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
Johnston JA Johnston Janet A JA
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
Kölsch H Kölsch Heike H
Heun R Heun Reinhard R
Schürmann B Schürmann Britta B
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
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
Davies G Davies Gail G
Harris SE Harris Sarah E SE
Starr JM Starr John M JM
Deary IJ Deary Ian J IJ
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
Jones L Jones Lesley L
Holmans PA Holmans Peter A PA
O'Donovan MC O'Donovan Michael C MC
Owen MJ Owen Michael J MJ
Williams J Williams Julie J
INVESTIGATORS
JOURNAL
VOLUME: 28
ISSUE: 2
TITLE: Journal of Alzheimer's disease : JAD
ISOABBREVIATION: J. Alzheimers Dis.
YEAR: 2012
MONTH:
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1875-8908
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: J Alzheimers Dis
COUNTRY: Netherlands
ISSNLINKING: 1387-2877
NLMUNIQUEID: 9814863
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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GRANTS
GRANTID AGENCY COUNTRY
095317 Wellcome Trust United Kingdom
BB/F019394/1 Biotechnology and Biological Sciences Research Council United Kingdom
G-0907 Parkinson's UK United Kingdom
G0601846 Medical Research Council United Kingdom
G0700704 Medical Research Council United Kingdom
G0700704/84698 Biotechnology and Biological Sciences Research Council United Kingdom
G0701075 Medical Research Council United Kingdom
G0900688 Medical Research Council United Kingdom
G0902227 Medical Research Council United Kingdom
MC_U123160651 Medical Research Council United Kingdom
MC_U123160657 Medical Research Council United Kingdom
P01 AG003991 NIA NIH HHS United States
P50 AG005681 NIA NIH HHS United States
Chief Scientist Office United Kingdom
Medical Research Council United Kingdom
Wellcome Trust United Kingdom
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Aged
Aged, 80 and over
Alzheimer Disease genetics
Amyloid beta-Protein Precursor genetics
Female genetics
Genetic Predisposition to Disease genetics
Genome-Wide Association Study genetics
Genotype genetics
Humans genetics
Male genetics
Meta-Analysis as Topic genetics
Odds Ratio genetics
Polymorphism, Single Nucleotide genetics
Presenilin-1 genetics
Presenilin-2 genetics
tau Proteins genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Amyloid beta-Protein Precursor
0 MAPT protein, human
0 PSEN1 protein, human
0 Presenilin-1
0 Presenilin-2
0 tau Proteins
OTHER ID's
OTHERID SOURCE
NIHMS592897 NLM
PMC4118466 NLM
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