@article{395b00a734a14c7b9c3cf8dda4cdb450,
title = "Influence of coding variability in APP-Aβ metabolism genes in sporadic Alzheimer's disease",
abstract = "The cerebral deposition of Aβ42, a neurotoxic proteolytic derivate of amyloid precursor protein (APP), is a central event in Alzheimer's disease (AD)(Amyloid hypothesis). Given the key role of APP-Aβ metabolism in ADpathogenesis, we selected29 genes involved in APP processing, Aβ degradation and clearance. We then used exome and genome sequencing to investigate the single independent (single-variant association test) and cumulative (gene-based association test) effect of coding variants in these genes as potential susceptibility factors for AD, in a cohort composed of 332 sporadic and mainly late-onset ADcases and 676 elderly controls from North America and the UK. Our study shows that common coding variability in these genes does not play a major role for the disease development. In the single-variant association analysis, the main hits, none of which statistically significant after multiple testing correction (1.9e-4-3 ",
author = "Celeste Sassi and Ridge, {Perry G.} and Nalls, {Michael A.} and Raphael Gibbs and Jinhui Ding and Lupton, {Michelle K.} and Claire Troakes and Katie Lunnon and Safa Al-Sarraj and Brown, {Kristelle S.} and Christopher Medway and Jenny Lord and James Turton and Kevin Morgan and Powell, {John F.} and Kauwe, {John S.} and Carlos Cruchaga and Jose Bras and Goate, {Alison M.} and Singleton, {Andrew B.} and Rita Guerreiro and John Hardy and Peter Passmore and David Craig and Janet Johnston and Bernadette McGuinness and Stephen Todd and Reinhard Heun and Heike K{\"o}lsch and Kehoe, {Patrick G.} and Hooper, {Nigel M.} and Vardy, {Emma R.L.C.} and Mann, {David M.} and James Lowe and {David Smith}, A. and Gordon Wilcock and Donald Warden and Clive Holmes",
note = "Funding Information: Tissue samples were supplied by The London Neurodegenerative Diseases Brain Bank, which receives funding from the MRC and as part of the Brains for Dementia Research programme, jointly funded by Alzheimer{\textquoteright}s Research UK and Alzheimer{\textquoteright}s Society. Funding Information: This study was supported by the Alzheimer's Research UK, the Medical Research Council (MRC), the Wellcome Trust/MRC Joint Call in Neurodegeneration Award (WT089698) to the UK Parkinson's Disease Consortium (whose members are from the University College London Institute of Neurology, the University of Sheffield, and the MRC Protein Phosphorylation Unit at the University of Dundee), grants (P50 AG016574, U01 AG006786, and R01 AG18023), the National Institute for Health Research Biomedical Research Unit in Dementia at University College London Hospitals, University College London; the Big Lottery (to Dr. Morgan); a fellowship from Alzheimer's Research UK (to Dr. Guerreiro); and the Intramural Research Programs of the National Institute on Aging and the National Institute of Neurological Disease and Stroke, National Institutes of Health (Department of Health and Human Services Project number, ZO1 AG000950-10). The MRC London Neurodegenerative Diseases Brain Bank and the Manchester Brain Bank from Brains for Dementia Research are jointly funded from ARUK and AS. The Alzheimer{\textquoteright}s Research UK (ARUK) Consortium: Peter Passmore, David Craig, Janet Johnston, Bernadette McGuinness, Stephen Todd, Queen{\textquoteright}s University Belfast, UK; Reinhard Heun, Royal Derby Hospital, UK; Heike K{\"o}lsch, University of Bonn, Germany; Patrick G. Kehoe, University of Bristol, UK; Nigel M. Hooper, University of Leeds, UK; Emma R.L.C. Vardy, University of Newcastle, UK; David M. Mann, Stuart Pickering-Brown, University of Manchester, UK; Kristelle Brown, James Lowe, Kevin Morgan, University of Nottingham, UK; A. David Smith, Gordon Wilcock, Donald Warden, University of Oxford (OPTIMA), UK; Clive Holmes, University of Southampton, UK. ",
year = "2016",
month = jun,
doi = "10.1371/journal.pone.0150079",
language = "English",
volume = "11",
journal = "PLoS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "6",
}