1. Influence of Coding Variability in APP-Aβ Metabolism Genes in Sporadic Alzheimer's Disease
- Author
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Sassi, Celeste, Ridge, Perry G, Medway, Christopher, Lord, Jenny, Turton, James, Consortium, ARUK, Morgan, Kevin, Powell, John F, Kauwe, John S, Cruchaga, Carlos, Bras, Jose, Goate, Alison M, Nalls, Michael A, Singleton, Andrew B, Guerreiro, Rita, Hardy, John, Gibbs, Raphael, Ding, Jinhui, Lupton, Michelle K, Troakes, Claire, Lunnon, Katie, Al-Sarraj, Safa, and Brown, Kristelle S
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Science ,metabolism [Amyloid beta-Peptides] ,genetics [Alzheimer Disease] ,Research and Analysis Methods ,Biochemistry ,Amyloid beta-Protein Precursor ,Elderly ,Alzheimer Disease ,metabolism [Amyloid beta-Protein Precursor] ,Mental Health and Psychiatry ,Medicine and Health Sciences ,Genetics ,genetics [Amyloid beta-Peptides] ,Humans ,Exome ,ddc:610 ,Genome Sequencing ,Molecular Biology Techniques ,Sequencing Techniques ,Molecular Biology ,Alleles ,Computational Neuroscience ,Damage Mechanics ,Coding Mechanisms ,Amyloid beta-Peptides ,Physics ,Computational Biology ,Classical Mechanics ,Biology and Life Sciences ,Catabolism ,Neurodegenerative Diseases ,Metabolism ,Neurology ,genetics [Amyloid beta-Protein Precursor] ,Age Groups ,Geriatrics ,Genetic Loci ,Physical Sciences ,People and Places ,Medicine ,Dementia ,Population Groupings ,metabolism [Alzheimer Disease] ,Research Article ,Neuroscience - 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 AD pathogenesis, we selected 29 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 AD cases 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
- Published
- 2015
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