dc.contributor.author | NOYCE, AJ | |
dc.contributor.author | International Parkinson's Disease Genomics Consortium (IPDGC) | |
dc.date.accessioned | 2019-04-26T16:17:31Z | |
dc.date.available | 2019-01-01 | |
dc.date.available | 2019-04-26T16:17:31Z | |
dc.date.issued | 2019-04-07 | |
dc.identifier.citation | Blauwendraat, C. et al (2019), Parkinson's disease age at onset genome‐wide association study: Defining heritability, genetic loci, and α‐synuclein mechanisms. Mov Disord. doi:10.1002/mds.27659 | en_US |
dc.identifier.issn | 0885-3185 | |
dc.identifier.uri | https://qmro.qmul.ac.uk/xmlui/handle/123456789/57074 | |
dc.description.abstract | Background:
Increasing evidence supports an extensive and complex genetic contribution to PD. Previous genome‐wide association studies (GWAS) have shed light on the genetic basis of risk for this disease. However, the genetic determinants of PD age at onset are largely unknown.
Objectives:
To identify the genetic determinants of PD age at onset.
Methods:
Using genetic data of 28,568 PD cases, we performed a genome‐wide association study based on PD age at onset.
Results:
We estimated that the heritability of PD age at onset attributed to common genetic variation was ∼0.11, lower than the overall heritability of risk for PD (∼0.27), likely, in part, because of the subjective nature of this measure. We found two genome‐wide significant association signals, one at SNCA and the other a protein‐coding variant in TMEM175, both of which are known PD risk loci and a Bonferroni‐corrected significant effect at other known PD risk loci, GBA, INPP5F/BAG3, FAM47E/SCARB2, and MCCC1. Notably, SNCA, TMEM175, SCARB2, BAG3, and GBA have all been shown to be implicated in α‐synuclein aggregation pathways. Remarkably, other well‐established PD risk loci, such as GCH1 and MAPT, did not show a significant effect on age at onset of PD.
Conclusions:
Overall, we have performed the largest age at onset of PD genome‐wide association studies to date, and our results show that not all PD risk loci influence age at onset with significant differences between risk alleles for age at onset. This provides a compelling picture, both within the context of functional characterization of disease‐linked genetic variability and in defining differences between risk alleles for age at onset, or frank risk for disease. © 2019 International Parkinson and Movement Disorder Society | en_US |
dc.description.sponsorship | Intramural Research Programs of the National Institute of Neurological Disorders and Stroke (NINDS) | en_US |
dc.description.sponsorship | National Institute on Aging (NIA) | en_US |
dc.description.sponsorship | National Institute of Environmental Health Sciences | en_US |
dc.description.sponsorship | National Institutes of Health, Department of Health and Human Services; project numbers 1ZIA‐NS003154, Z01‐AG000949‐02, and Z01‐ES101986 | en_US |
dc.description.sponsorship | Department of Defense (award W81XWH‐09‐2‐0128) | en_US |
dc.description.sponsorship | Michael J Fox Foundation for Parkinson's Research | en_US |
dc.description.sponsorship | National Institutes of Health grants R01NS037167, R01CA141668, and P50NS071674 | en_US |
dc.description.sponsorship | American Parkinson Disease Association (APDA) | en_US |
dc.description.sponsorship | Barnes Jewish Hospital Foundation | en_US |
dc.description.sponsorship | Greater St Louis Chapter of the APDA | en_US |
dc.language.iso | en | en_US |
dc.publisher | Wiley | en_US |
dc.relation.ispartof | Movement Disorders | |
dc.relation.isreplacedby | 123456789/57077 | |
dc.relation.isreplacedby | https://qmro.qmul.ac.uk/xmlui/handle/123456789/57077 | |
dc.rights | "This is the peer reviewed version of the following article: Blauwendraat et al for the International Parkinson's Disease Genomics Consortium (IPDGC). Parkinson's disease age at onset genome‐wide association study: Defining heritability, genetic loci, and α‐synuclein mechanisms. Mov Disord. doi:10.1002/mds.27659. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions." | |
dc.subject | age at onset | en_US |
dc.subject | GBA | en_US |
dc.subject | Parkinson's disease | en_US |
dc.subject | SNCA | en_US |
dc.subject | TMEM175 | en_US |
dc.title | Parkinson's disease age at onset genome‐wide association study: Defining heritability, genetic loci, and α‐synuclein mechanisms | en_US |
dc.title.alternative | Parkinson disease age at onset GWAS: defining heritability, genetic loci and α-synuclein mechanisms | en_US |
dc.type | Article | en_US |
dc.identifier.doi | https://doi.org/10.1002/mds.27659 | |
pubs.notes | Not known | en_US |
pubs.publication-status | Accepted | en_US |
dcterms.dateAccepted | 2019-01-01 | |
rioxxterms.funder | Default funder | en_US |
rioxxterms.identifier.project | Default project | en_US |