Sassi, C;
Nalls, MA;
Ridge, PG;
Gibbs, JR;
Ding, J;
Lupton, MK;
Troakes, C;
... Hardy, J; + view all
(2016)
ABCA7 p.G215S as potential protective factor for Alzheimer's disease.
Neurobiology of Aging
10.1016/j.neurobiolaging.2016.04.004.
Preview |
Text (Article)
1-s2.0-S0197458016300318-main.pdf - Published Version Download (751kB) | Preview |
Preview |
Text (Supplementary data)
mmc1-3.pdf Download (1MB) | Preview |
Abstract
Genome-wide association studies (GWASs) have been effective approaches to dissect common genetic variability underlying complex diseases in a systematic and unbiased way. Recently, GWASs have led to the discovery of over 20 susceptibility loci for Alzheimer's disease (AD). Despite the evidence showing the contribution of these loci to AD pathogenesis, their genetic architecture has not been extensively investigated, leaving the possibility that low frequency and rare coding variants may also occur and contribute to the risk of disease. We have used exome and genome sequencing data to analyze the single independent and joint effect of rare and low-frequency protein coding variants in 9 AD GWAS loci with the strongest effect sizes after APOE (BIN1, CLU, CR1, PICALM, MS4A6A, ABCA7, EPHA1, CD33, and CD2AP) in a cohort of 332 sporadic AD cases and 676 elderly controls of British and North-American ancestry. We identified coding variability in ABCA7 as contributing to AD risk. This locus harbors a low-frequency coding variant (p.G215S, rs72973581, minor allele frequency = 4.3%) conferring a modest but statistically significant protection against AD (p-value = 0.024, odds ratio = 0.57, 95% confidence interval = 0.41-0.80). Notably, our results are not driven by an enrichment of loss of function variants in ABCA7, recently reported as main pathogenic factor underlying AD risk at this locus. In summary, our study confirms the role of ABCA7 in AD and provides new insights that should address functional studies.
| Type: | Article |
|---|---|
| Title: | ABCA7 p.G215S as potential protective factor for Alzheimer's disease |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.neurobiolaging.2016.04.004 |
| Publisher version: | http://dx.doi.org/10.1016/j.neurobiolaging.2016.04... |
| Language: | English |
| Additional information: | © 2016 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | ABCA7, Alzheimer's disease (AD), Genome-wide association studies (GWASs), Protective variant, Whole exome sequencing (WES), Whole genome sequencing (WGS) |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1499807 |
Archive Staff Only
 |
View Item |
