Abstract

Objective: Parkinson's disease (PD) is a complex neurodegenerative disorder. Men are on average ~ 1.5 times more likely to develop PD compared to women with European ancestry. Over the years, genomewide association studies (GWAS) have identified numerous genetic risk factors for PD, however, it is unclear whether genetics contribute to disease etiology in a sex-specific manner. Methods: In an effort to study sex-specific genetic factors associated with PD, we explored 2 large genetic datasets from the International Parkinson's Disease Genomics Consortium and the UK Biobank consisting of 13,020 male PD cases, 7,936 paternal proxy cases, 89,660 male controls, 7,947 female PD cases, 5,473 maternal proxy cases, and 90,662 female controls. We performed GWAS meta-analyses to identify distinct patterns of genetic risk contributing to disease in male versus female PD cases. Results: In total, 19 genomewide significant regions were identified and no sex-specific effects were observed. A high genetic correlation between the male and female PD GWAS were identified (rg = 0.877) and heritability estimates were identical between male and female PD cases (~ 20%). Interpretation: We did not detect any significant genetic differences between male or female PD cases. Our study does not support the notion that common genetic variation on the autosomes could explain the difference in prevalence of PD between males and females cases at least when considering the current sample size under study. Further studies are warranted to investigate the genetic architecture of PD explained by X and Y chromosomes and further evaluate environmental effects that could potentially contribute to PD etiology in male versus female patients. ANN NEUROL 2021;90:41–48.

Original languageEnglish
Pages (from-to)35-42
Number of pages8
JournalAnnals of Neurology
Volume90
Issue number1
DOIs
StatePublished - Jul 2021

Funding

FundersFunder number
Forschungszentrum für Umwelt und Gesundheit
German Federal Ministry of Education, Science, Research, and Technology
Greater St Louis Chapter of the APDA
International Parkinson Disease Genomics Consortium
National Institute of Neurological Disorders and Stroke Human Genetics Resource Center
Wellcome Trust Case
National Institutes of Health
U.S. Department of DefenseW81XWH‐09‐2‐0128, R01CA141668
U.S. Department of Defense
U.S. Department of Health and Human Services1ZIA‐NS003154, Z01‐ES101986, Z01‐AG000949‐02
U.S. Department of Health and Human Services
National Institute on Aging
National Institute of Neurological Disorders and StrokeP50NS071674, R01NS037167
National Institute of Neurological Disorders and Stroke
National Institute of Environmental Health Sciences
Michael J. Fox Foundation for Parkinson's Research
American Parkinson Disease Association
Foundation for Barnes-Jewish Hospital
Helsingin Yliopisto
Helsingin ja Uudenmaan Sairaanhoitopiiri
McGill University
Wellcome Trust085475, 076113, 090355
Wellcome Trust
EU Joint Programme – Neurodegenerative Disease Research01ED1406
EU Joint Programme – Neurodegenerative Disease Research
Consortium canadien en neurodégénérescence associée au vieillissement
Parkinson Society Canada
Medical Research CouncilG1100643, G0700943
Medical Research Council
Parkinson's UK8047, J‐0804
Parkinson's UK
Bundesministerium für Bildung und Forschung031A430A
Bundesministerium für Bildung und Forschung
Sigrid Juséliuksen Säätiö
Canada First Research Excellence Fund

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