Genome-wide Association and Meta-analysis of Age at Onset in Parkinson Disease: Evidence From the COURAGE-PD Consortium.
Journal
Neurology
ISSN: 1526-632X
Titre abrégé: Neurology
Pays: United States
ID NLM: 0401060
Informations de publication
Date de publication:
16 08 2022
16 08 2022
Historique:
received:
17
11
2021
accepted:
23
03
2022
entrez:
15
8
2022
pubmed:
16
8
2022
medline:
18
8
2022
Statut:
ppublish
Résumé
Considerable heterogeneity exists in the literature concerning genetic determinants of the age at onset (AAO) of Parkinson disease (PD), which could be attributed to a lack of well-powered replication cohorts. The previous largest genome-wide association studies (GWAS) identified A meta-analysis was performed on PD AAO GWAS of 30 populations of predominantly European ancestry from the Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson's Disease (COURAGE-PD) Consortium. This was followed by combining our study with the largest publicly available European ancestry dataset compiled by the International Parkinson Disease Genomics Consortium (IPDGC). The COURAGE-PD Consortium included a cohort of 8,535 patients with PD (91.9%: Europeans and 9.1%: East Asians). The average AAO in the COURAGE-PD dataset was 58.9 years (SD = 11.6), with an underrepresentation of females (40.2%). The heritability estimate for AAO in COURAGE-PD was 0.083 (SE = 0.057). None of the loci reached genome-wide significance ( Our study further refines the genetic architecture of Chr 4 underlying the AAO of the PD phenotype through the identification of
Sections du résumé
BACKGROUND AND OBJECTIVES
Considerable heterogeneity exists in the literature concerning genetic determinants of the age at onset (AAO) of Parkinson disease (PD), which could be attributed to a lack of well-powered replication cohorts. The previous largest genome-wide association studies (GWAS) identified
METHODS
A meta-analysis was performed on PD AAO GWAS of 30 populations of predominantly European ancestry from the Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson's Disease (COURAGE-PD) Consortium. This was followed by combining our study with the largest publicly available European ancestry dataset compiled by the International Parkinson Disease Genomics Consortium (IPDGC).
RESULTS
The COURAGE-PD Consortium included a cohort of 8,535 patients with PD (91.9%: Europeans and 9.1%: East Asians). The average AAO in the COURAGE-PD dataset was 58.9 years (SD = 11.6), with an underrepresentation of females (40.2%). The heritability estimate for AAO in COURAGE-PD was 0.083 (SE = 0.057). None of the loci reached genome-wide significance (
DISCUSSION
Our study further refines the genetic architecture of Chr 4 underlying the AAO of the PD phenotype through the identification of
Identifiants
pubmed: 35970579
pii: WNL.0000000000200699
doi: 10.1212/WNL.0000000000200699
pmc: PMC9484604
doi:
Types de publication
Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e698-e710Informations de copyright
Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
Références
Nature. 2007 Mar 1;446(7131):41-5
pubmed: 17287729
Cytometry B Clin Cytom. 2013 Jul-Aug;84(4):207-17
pubmed: 23576305
Lancet Neurol. 2019 Dec;18(12):1091-1102
pubmed: 31701892
Bioinformatics. 2016 May 1;32(9):1423-6
pubmed: 27153000
Bioinformatics. 2010 Sep 1;26(17):2190-1
pubmed: 20616382
Neurology. 2012 Aug 14;79(7):659-67
pubmed: 22786590
Bioinformatics. 2010 Sep 15;26(18):2336-7
pubmed: 20634204
Proc Natl Acad Sci U S A. 2017 Feb 28;114(9):2389-2394
pubmed: 28193887
Nat Protoc. 2020 Sep;15(9):2759-2772
pubmed: 32709988
Biochem Soc Trans. 2007 Feb;35(Pt 1):109-14
pubmed: 17233614
Brain. 2021 Mar 3;144(2):462-472
pubmed: 33349842
Science. 1997 Jun 27;276(5321):2045-7
pubmed: 9197268
J Natl Cancer Inst. 1959 Apr;22(4):719-48
pubmed: 13655060
Control Clin Trials. 1986 Sep;7(3):177-88
pubmed: 3802833
Immunol Lett. 2019 Jan;205:59-64
pubmed: 29936181
Brain. 2019 Jan 1;143(1):234-248
pubmed: 31755958
Nat Neurosci. 2014 Oct;17(10):1418-1428
pubmed: 25174004
Neuropsychiatr Dis Treat. 2019 Apr 30;15:1089-1102
pubmed: 31118642
Ann Neurol. 2018 Jul;84(1):117-129
pubmed: 30146727
Front Behav Neurosci. 2014 Apr 22;8:133
pubmed: 24795584
Ann Neurol. 2021 Jul;90(1):22-34
pubmed: 33583074
Mov Disord. 2019 Jun;34(6):866-875
pubmed: 30957308
Nat Genet. 2015 Mar;47(3):291-5
pubmed: 25642630
Neurol Sci. 2020 Feb;41(2):271-280
pubmed: 31758346
Nature. 2016 May 5;533(7601):95-9
pubmed: 27096366
Mol Cell Probes. 2016 Dec;30(6):386-396
pubmed: 27818248
Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5325-9
pubmed: 8202488
Lancet. 2021 Jun 12;397(10291):2284-2303
pubmed: 33848468
BMC Neurosci. 2017 Mar 24;18(1):35
pubmed: 28340569
Mov Disord. 2021 Jul;36(7):1689-1695
pubmed: 33760272
Front Behav Neurosci. 2017 May 03;11:75
pubmed: 28515684
Nat Genet. 2009 Dec;41(12):1303-7
pubmed: 19915576
Stat Med. 2002 Jan 15;21(1):35-50
pubmed: 11782049
Nat Genet. 2017 Oct;49(10):1511-1516
pubmed: 28892059
Nat Genet. 2014 Sep;46(9):989-93
pubmed: 25064009
Mov Disord. 2021 Sep;36(9):2077-2084
pubmed: 33884653
JAMA Neurol. 2020 Jun 1;77(6):746-754
pubmed: 32310270
CNS Neurosci Ther. 2019 Apr;25(4):422-429
pubmed: 30676692
Science. 2015 May 8;348(6235):648-60
pubmed: 25954001
Genet Epidemiol. 2019 Oct;43(7):815-830
pubmed: 31332826