A Multi-center Genome-wide Association Study of Cervical Dystonia.
cervical dystonia
genome-wide association study (GWAS)
movement disorder
rare disease
Journal
Movement disorders : official journal of the Movement Disorder Society
ISSN: 1531-8257
Titre abrégé: Mov Disord
Pays: United States
ID NLM: 8610688
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
revised:
24
06
2021
received:
27
08
2019
accepted:
12
07
2021
pubmed:
29
7
2021
medline:
17
3
2022
entrez:
28
7
2021
Statut:
ppublish
Résumé
Several monogenic causes for isolated dystonia have been identified, but they collectively account for only a small proportion of cases. Two genome-wide association studies have reported a few potential dystonia risk loci; but conclusions have been limited by small sample sizes, partial coverage of genetic variants, or poor reproducibility. To identify robust genetic variants and loci in a large multicenter cervical dystonia cohort using a genome-wide approach. We performed a genome-wide association study using cervical dystonia samples from the Dystonia Coalition. Logistic and linear regressions, including age, sex, and population structure as covariates, were employed to assess variant- and gene-based genetic associations with disease status and age at onset. We also performed a replication study for an identified genome-wide significant signal. After quality control, 919 cervical dystonia patients compared with 1491 controls of European ancestry were included in the analyses. We identified one genome-wide significant variant (rs2219975, chromosome 3, upstream of COL8A1, P-value 3.04 × 10 The genetic underpinnings of cervical dystonia are complex and likely consist of multiple distinct variants of small effect sizes. Larger sample sizes may be needed to provide sufficient statistical power to address the presumably multi-genic etiology of cervical dystonia. © 2021 International Parkinson and Movement Disorder Society.
Sections du résumé
BACKGROUND
Several monogenic causes for isolated dystonia have been identified, but they collectively account for only a small proportion of cases. Two genome-wide association studies have reported a few potential dystonia risk loci; but conclusions have been limited by small sample sizes, partial coverage of genetic variants, or poor reproducibility.
OBJECTIVE
To identify robust genetic variants and loci in a large multicenter cervical dystonia cohort using a genome-wide approach.
METHODS
We performed a genome-wide association study using cervical dystonia samples from the Dystonia Coalition. Logistic and linear regressions, including age, sex, and population structure as covariates, were employed to assess variant- and gene-based genetic associations with disease status and age at onset. We also performed a replication study for an identified genome-wide significant signal.
RESULTS
After quality control, 919 cervical dystonia patients compared with 1491 controls of European ancestry were included in the analyses. We identified one genome-wide significant variant (rs2219975, chromosome 3, upstream of COL8A1, P-value 3.04 × 10
CONCLUSION
The genetic underpinnings of cervical dystonia are complex and likely consist of multiple distinct variants of small effect sizes. Larger sample sizes may be needed to provide sufficient statistical power to address the presumably multi-genic etiology of cervical dystonia. © 2021 International Parkinson and Movement Disorder Society.
Identifiants
pubmed: 34320236
doi: 10.1002/mds.28732
pmc: PMC8688173
mid: NIHMS1724288
doi:
Substances chimiques
DENND1A protein, human
0
Death Domain Receptor Signaling Adaptor Proteins
0
Guanine Nucleotide Exchange Factors
0
Types de publication
Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2795-2801Subventions
Organisme : NINDS NIH HHS
ID : R21 NS096455
Pays : United States
Organisme : NINDS NIH HHS
ID : U54 NS116025
Pays : United States
Organisme : NCATS NIH HHS
ID : KL2 TR001080
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH120262
Pays : United States
Organisme : NCATS NIH HHS
ID : U54 TR001456
Pays : United States
Organisme : NINDS NIH HHS
ID : U54 NS065701
Pays : United States
Organisme : NIDA NIH HHS
ID : UG3 DA048502
Pays : United States
Informations de copyright
© 2021 International Parkinson and Movement Disorder Society.
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