The Role of Variation at A beta PP, PSEN1, PSEN2, and MAPT in Late Onset Alzheimer's Disease

Amy Gerrish; Giancarlo Russo; Alexander Richards; Valentina Moskvina; Dobril Ivanov; Denise Harold; Rebecca Sims; Richard Abraham; Paul Hollingworth; Jade Chapman; Marian Hamshere; Jaspreet Singh Pahwa; Kimberley Dowzell; Amy Williams; Nicola Jones; Charlene Thomas; Alexandra Stretton; Angharad R. Morgan; Simon Lovestone; John Powell; Petroula Proitsi; Michelle K. Lupton; Carol Brayne; David C. Rubinsztein; Michael Gill; Brian Lawlor; Aoibhinn Lynch; Kevin Morgan; Kristelle S. Brown; Peter A. Passmore; David Craig; Bernadette McGuinness; Stephen Todd; Janet A. Johnston; Clive Holmes; David Mann; A. David Smith; Seth Love; Patrick G. Kehoe; John Hardy; Simon Mead; Nick Fox; Martin Rossor; John Collinge; Wolfgang Maier; Frank Jessen; Heike Koelsch; Reinhard Heun; Britta Schuermann; Hendrik van den Bussche; Isabella Heuser; Johannes Kornhuber; Jens Wiltfang; Martin Dichgans; Lutz Froelich; Harald Hampel; Michael Huell; Dan Rujescu; Alison M. Goate; John S. K. Kauwe; Carlos Cruchaga; Petra Nowotny; John C. Morris; Kevin Mayo; Gill Livingston; Nicholas J. Bass; Hugh Gurling; Andrew McQuillin; Rhian Gwilliam; Panagiotis Deloukas; Gail Davies; Sarah E. Harris; John M. Starr; Ian J. Deary; Ammar Al-Chalabi; Christopher E. Shaw; Magda Tsolaki; Andrew B. Singleton; Rita Guerreiro; Thomas W. Muehleisen; Markus M. Noethen; Susanne Moebus; Karl-Heinz Joeckel; Norman Klopp; H-Erich Wichmann; Minerva M. Carrasquillo; V. Shane Pankratz; Steven G. Younkin; Lesley Jones; Peter A. Holmans; Michael C. O'Donovan; Michael J. Owen; Julie Williams

doi:10.3233/JAD-2011-110824

Back

The Role of Variation at A beta PP, PSEN1, PSEN2, and MAPT in Late Onset Alzheimer's Disease

Journal article

Open access

Peer reviewed

The Role of Variation at A beta PP, PSEN1, PSEN2, and MAPT in Late Onset Alzheimer's Disease

Amy Gerrish, Giancarlo Russo, Alexander Richards, Valentina Moskvina, Dobril Ivanov, Denise Harold, Rebecca Sims, Richard Abraham, Paul Hollingworth, Jade Chapman, …

Journal of Alzheimer's disease, Vol.28(2), pp.377-387

01/01/2012

DOI: https://doi.org/10.3233/JAD-2011-110824

PMCID: PMC4118466

PMID: 22027014

Abstract

Life Sciences & Biomedicine

Neurosciences

Neurosciences & Neurology

Science & Technology

Rare mutations in A beta PP, 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 A beta PP, 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.

Files and links (1)

url

https://doi.org/10.3233/JAD-2011-110824View

Published (Version of record) Open

Metrics

1 Record Views

See more details

Details

Title: The Role of Variation at A beta PP, PSEN1, PSEN2, and MAPT in Late Onset Alzheimer's Disease
Creators - without role: Amy Gerrish - Cardiff University
Giancarlo Russo - Cardiff University
Alexander Richards - Cardiff University
Valentina Moskvina - Cardiff University
Dobril Ivanov - Cardiff University
Denise Harold - Cardiff University
Rebecca Sims - Cardiff University
Richard Abraham - Cardiff University
Paul Hollingworth - Cardiff University
Jade Chapman - Cardiff University
Marian Hamshere - Cardiff University
Jaspreet Singh Pahwa - Cardiff University
Kimberley Dowzell - Cardiff University
Amy Williams - Cardiff University
Nicola Jones - Cardiff University
Charlene Thomas - Cardiff University
Alexandra Stretton - Cardiff University
Angharad R. Morgan - Cardiff University
Simon Lovestone
John Powell - Kings Coll London, Inst Psychiat, Dept Neurosci, London WC2R 2LS, England
Petroula Proitsi - Kings Coll London, Inst Psychiat, Dept Neurosci, London WC2R 2LS, England
Michelle K. Lupton - Kings Coll London, Inst Psychiat, Dept Neurosci, London WC2R 2LS, England
Carol Brayne - University of Cambridge
David C. Rubinsztein - University of Cambridge
Michael Gill - St James Hosp, Mercers Inst Res Aging, Dublin 8, Ireland
Brian Lawlor - St James Hosp, Mercers Inst Res Aging, Dublin 8, Ireland
Aoibhinn Lynch - St James Hosp, Mercers Inst Res Aging, Dublin 8, Ireland
Kevin Morgan - University of Nottingham
Kristelle S. Brown - University of Nottingham
Peter A. Passmore - Queens University
David Craig - Queens University
Bernadette McGuinness - Queens University
Stephen Todd - Queens University
Janet A. Johnston - Queens University
Clive Holmes - University of Southampton
David Mann - University of Manchester
A. David Smith - University of Oxford
Seth Love - University of Bristol
Patrick G. Kehoe - University of Bristol
John Hardy - Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England
Simon Mead - MRC Prion Unit
Nick Fox - UCL Inst Neurol, Dept Neurodegenerat Dis, Dementia Res Ctr, London, England
Martin Rossor - UCL Inst Neurol, Dept Neurodegenerat Dis, Dementia Res Ctr, London, England
John Collinge - UCL, Inst Neurol, Dept Neurodegenerat Dis, London WC1E 6BT, England
Wolfgang Maier - University of Bonn
Frank Jessen - University of Bonn
Heike Koelsch - University of Bonn
Reinhard Heun - University of Bonn
Britta Schuermann - University of Bonn
Hendrik van den Bussche - Eppendorf
Isabella Heuser - Charité - Universitätsmedizin Berlin
Johannes Kornhuber - Univ Erlangen Nurnberg, Dept Psychiat & Psychotherapy, Erlangen, Germany
Jens Wiltfang - University of Duisburg-Essen
Martin Dichgans - Klinikum Univ Munchen, Inst Stroke & Dementia Res, Munich, Germany
Lutz Froelich - Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Geriatr Psychiat, D-6800 Mannheim, Germany
Harald Hampel - Goethe University Frankfurt
Michael Huell - Univ Munich, Dept Psychiat, D-8000 Munich, Germany
Dan Rujescu - Univ Munich, Dept Psychiat, D-8000 Munich, Germany
Alison M. Goate - Supreme Council Of Health
John S. K. Kauwe - Brigham Young University
Carlos Cruchaga - Supreme Council Of Health
Petra Nowotny - Supreme Council Of Health
John C. Morris - Supreme Council Of Health
Kevin Mayo - Supreme Council Of Health
Gill Livingston - UCL, Mental Hlth Unit, London, England
Nicholas J. Bass - UCL, Mental Hlth Unit, London, England
Hugh Gurling - UCL, Mental Hlth Unit, London, England
Andrew McQuillin - UCL, Mental Hlth Unit, London, England
Rhian Gwilliam - Wellcome Sanger Institute
Panagiotis Deloukas - Wellcome Sanger Institute
Gail Davies - University of Edinburgh
Sarah E. Harris - University of Edinburgh
John M. Starr - University of Edinburgh
Ian J. Deary - University of Edinburgh
Ammar Al-Chalabi - Massachusetts Rehabilitation Commission
Christopher E. Shaw - Massachusetts Rehabilitation Commission
Magda Tsolaki - Aristotle University of Thessaloniki
Andrew B. Singleton - NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA
Rita Guerreiro - NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA
Thomas W. Muehleisen - University of Bonn
Markus M. Noethen - University of Bonn
Susanne Moebus - University of Duisburg-Essen
Karl-Heinz Joeckel - University of Duisburg-Essen
Norman Klopp - Helmholtz Zentrum München
H-Erich Wichmann - Helmholtz Zentrum München
Minerva M. Carrasquillo - College Station Medical Center
V. Shane Pankratz - Mayo Clin & Mayo Fdn, Div Biomed Stat & Informat, Rochester, MN 55905 USA
Steven G. Younkin - College Station Medical Center
Lesley Jones - Cardiff University
Peter A. Holmans - Cardiff University
Michael C. O'Donovan - Cardiff University
Michael J. Owen - Cardiff University
Julie Williams - Cardiff University
Publication Details: Journal of Alzheimer's disease, Vol.28(2), pp.377-387
Publisher: Ios Press
Number of pages: 11
Grant note: Heinz Nixdorf Foundation Welsh Assembly Government German Federal Ministry of Education and Research (BMBF); Federal Ministry of Education & Research (BMBF) Royal College of Physicians-Dunhill Medical Trust; Dunhill Medical Trust Helmholtz Zentrum Munchen; Helmholtz Association MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) US National Institutes of Health (NIH); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA BMBF; Federal Ministry of Education & Research (BMBF) Trinity College group Alfried Krupp von Bohlen und Halbach-Stiftung Bristol Research into Alzheimer's and Care of the Elderly German National Genome Research Network German Research Center for Environmental Health ARUK Ulster Garden Villages ESRC; UK Research & Innovation (UKRI); Economic & Social Research Council (ESRC) Barnes Jewish Foundation National Institute on Aging; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) Juvenile Diabetes Research Foundation International; Juvenile Diabetes Research Foundation NF-SI-0611-10084; NF-SI-0508-10123 / National Institute for Health Research; National Institute for Health Research (NIHR) Charles and Joanne Knight Alzheimer's Research Initiative National Human Genome Research Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI) G-0907 / Parkinson's UK Wellcome Trust NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Royal Society Competence Network Dementia and Competence Network Degenerative Dementia Chief Scientist Office of the Scottish Government BB/F019394/1 / Biotechnology and Biological Sciences Research Council; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC) Alzheimer's Society National Institute of Child Health and Human Development; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) Northern Ireland Research and Development Office ART-RF2007-3; ART-BIG2009-1; ART-PPG2011A-14; ART-PG2010-1 / Alzheimers Research UK; Alzheimer's Research UK (ARUK) US National Institute of Neurological Disorders and Stroke; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) G0700704; MC_U123160657; G0601846; MC_U123160651; G0701075; G0902227; G0900688 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) Lundbeck SA; Lundbeck Corporation Motor Neurone Disease Association EPSRC; UK Research & Innovation (UKRI); Engineering & Physical Sciences Research Council (EPSRC) BB/F019394/1 / BBSRC; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC) Palumbo Professorship in AD Research Munich Center of Health Sciences UK's Biotechnology and Biological Sciences Research Council (BBSRC); UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC) Medical Research Council (MRC, UK); UK Research & Innovation (UKRI); Medical Research Council UK (MRC) MC_U123160657; G0900688; G0902227; G0700704; G0801418B; MC_U123160651; G0700704B; G0701075; G0601846 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) Alzheimer's Research UK (ARUK) Oxford Project BBSRC; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC) US National Institute of Diabetes and Digestive and Kidney Diseases; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) National Institute of Allergy and Infectious Diseases; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) American Federation for Aging Research for the Paul Beeson Career Development Awards
Identifiers: 9939252708331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article