Analysis of Y chromosome haplogroups in Parkinson's disease.

Parkinson’s disease chromosome Y genetics

Journal

Brain communications
ISSN: 2632-1297
Titre abrégé: Brain Commun
Pays: England
ID NLM: 101755125

Informations de publication

Date de publication:
2022
Historique:
received: 03 03 2022
revised: 01 07 2022
accepted: 27 10 2022
entrez: 17 11 2022
pubmed: 18 11 2022
medline: 18 11 2022
Statut: epublish

Résumé

Parkinson's disease is a complex neurodegenerative disorder that is about 1.5 times more prevalent in males than females. Extensive work has been done to identify the genetic risk factors behind Parkinson's disease on autosomes and more recently on Chromosome X, but work remains to be done on the male-specific Y chromosome. In an effort to explore the role of the Y chromosome in Parkinson's disease, we analysed whole-genome sequencing data from the Accelerating Medicines Partnership-Parkinson's disease initiative (1466 cases and 1664 controls), genotype data from NeuroX (3491 cases and 3232 controls) and genotype data from UKBiobank (182 517 controls, 1892 cases and 3783 proxy cases), all consisting of male European ancestry samples. We classified sample Y chromosomes by haplogroup using three different tools for comparison (Snappy, Yhaplo and Y-LineageTracker) and meta-analysed this data to identify haplogroups associated with Parkinson's disease. This was followed up with a Y-chromosome association study to identify specific variants associated with disease. We also analysed blood-based RNASeq data obtained from the Accelerating Medicines Partnership-Parkinson's disease initiative (1020 samples) and RNASeq data obtained from the North American Brain Expression Consortium (171 samples) to identify Y-chromosome genes differentially expressed in cases, controls, specific haplogroups and specific tissues. RNASeq analyses suggest Y-chromosome gene expression differs between brain and blood tissues but does not differ significantly in cases, controls or specific haplogroups. Overall, we did not find any strong associations between Y-chromosome genetics and Parkinson's disease, suggesting the explanation for the increased prevalence in males may lie elsewhere.

Identifiants

pubmed: 36387750
doi: 10.1093/braincomms/fcac277
pii: fcac277
pmc: PMC9665271
doi:

Types de publication

Journal Article

Langues

eng

Pagination

fcac277

Subventions

Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : Intramural NIH HHS
ID : Z01 ES101986
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA AG000935
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA NS003154
Pays : United States
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom

Informations de copyright

Published by Oxford University Press on behalf of the Guarantors of Brain 2022.

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Auteurs

Francis P Grenn (FP)

Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.

Mary B Makarious (MB)

Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK.
UCL Movement Disorders Centre, University College London, London, UK.

Sara Bandres-Ciga (S)

Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.

Hirotaka Iwaki (H)

Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Data Tecnica International, Washington, DC, USA.

Andrew B Singleton (AB)

Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.

Mike A Nalls (MA)

Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Data Tecnica International, Washington, DC, USA.

Cornelis Blauwendraat (C)

Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Integrative Neurogenomics Unit, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.

Classifications MeSH