| Title: | Investigation of Autosomal Genetic Sex Differences in Parkinson's Disease |
| Journal: | Annals of Neurology |
| Published: | 24 May 2021 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/33901317/ |
| DOI: | https://doi.org/10.1002/ana.26090 |
| URL: | https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ana.26090 |
Publication 5278
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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.</p>
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.</p>
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%).</p>
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.</p>
10 Keywords
- Aged
- Female
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Genotype
- Humans
- Male
- Middle Aged
- Parkinson Disease
- Sex Characteristics
210 Authors
- Cornelis Blauwendraat
- Hirotaka Iwaki
- Mary B. Makarious
- Sara Bandres-Ciga
- Hampton L. Leonard
- Francis P. Grenn
- Julie Lake
- Lynne Krohn
- Manuela Tan
- Jonggeol J. Kim
- Jesse R. Gibbs
- Dena G. Hernandez
- Jennifer A. Ruskey
- Lasse Pihlstrøm
- Mathias Toft
- Jacobus J. van Hilten
- Johan Marinus
- Claudia Schulte
- Kathrin Brockmann
- Manu Sharma
- Ari Siitonen
- Kari Majamaa
- Johanna Eerola-Rautio
- Pentti J. Tienari
- Donald G. Grosset
- Suzanne Lesage
- Jean-Christophe Corvol
- Alexis Brice
- Nick Wood
- John Hardy
- Ziv Gan-Or
- Peter Heutink
- Thomas Gasser
- Huw R. Morris
- Alastair J. Noyce
- Mike A. Nalls
- Andrew B. Singleton
- Alastair J. Noyce
- Rauan Kaiyrzhanov
- Ben Middlehurst
- Demis A. Kia
- Manuela Tan
- Henry Houlden
- Catherine S. Storm
- Huw R. Morris
- Helene Plun-Favreau
- Peter Holmans
- John Hardy
- Daniah Trabzuni
- John Quinn
- Vivien Bubb
- Kin Y. Mok
- Kerri J. Kinghorn
- Nicholas W. Wood
- Patrick Lewis
- Sebastian R. Schreglmann
- Ruth Lovering
- Lea R'Bibo
- Claudia Manzoni
- Mie Rizig
- Mina Ryten
- Sebastian Guelfi
- Valentina Escott-Price
- Viorica Chelban
- Thomas Foltynie
- Nigel Williams
- Karen E. Morrison
- Carl Clarke
- Kirsten Harvey
- Benjamin M. Jacobs
- Alexis Brice
- Fabrice Danjou
- Suzanne Lesage
- Jean-Christophe Corvol
- Maria Martinez
- Claudia Schulte
- Kathrin Brockmann
- Javier Simón-Sánchez
- Peter Heutink
- Patrizia Rizzu
- Manu Sharma
- Thomas Gasser
- Susanne A. Schneider
- Mark R. Cookson
- Sara Bandres-Ciga
- Cornelis Blauwendraat
- David W. Craig
- Kimberley Billingsley
- Mary B. Makarious
- Derek P. Narendra
- Faraz Faghri
- J. Raphael Gibbs
- Dena G. Hernandez
- Kendall Van Keuren-Jensen
- Joshua M. Shulman
- Hirotaka Iwaki
- Hampton L. Leonard
- Mike A. Nalls
- Laurie Robak
- Jose Bras
- Rita Guerreiro
- Steven Lubbe
- Timothy Troycoco
- Steven Finkbeiner
- Niccolo E. Mencacci
- Codrin Lungu
- Andrew B. Singleton
- Sonja W. Scholz
- Xylena Reed
- Ryan J. Uitti
- Owen A. Ross
- Francis P. Grenn
- Anni Moore
- Roy N. Alcalay
- Zbigniew K. Wszolek
- Ziv Gan-Or
- Guy A. Rouleau
- Lynne Krohn
- Kheireddin Mufti
- Jacobus J. van Hilten
- Johan Marinus
- Astrid D. Adarmes-Gómez
- Miquel Aguilar
- Ignacio Alvarez
- Victoria Alvarez
- Francisco Javier Barrero
- Jesús Alberto Bergareche Yarza
- Inmaculada Bernal-Bernal
- Marta Blazquez
- Marta Bonilla-Toribio
- Juan A. Botía
- María Teresa Boungiorno
- Dolores Buiza-Rueda
- Ana Cámara
- Fátima Carrillo
- Mario Carrión-Claro
- Debora Cerdan
- Jordi Clarimón
- Yaroslau Compta
- Monica Diez-Fairen
- Oriol Dols-Icardo
- Jacinto Duarte
- Raquel Duran
- Francisco Escamilla-Sevilla
- Mario Ezquerra
- Cici Feliz
- Manel Fernández
- Rubén Fernández-Santiago
- Ciara Garcia
- Pedro García-Ruiz
- Pilar Gómez-Garre
- Maria Jose Gomez Heredia
- Isabel Gonzalez-Aramburu
- Ana Gorostidi Pagola
- Janet Hoenicka
- Jon Infante
- Silvia Jesús
- Adriano Jimenez-Escrig
- Jaime Kulisevsky
- Miguel A. Labrador-Espinosa
- Jose Luis Lopez-Sendon
- Adolfo López de Munain Arregui
- Daniel Macias
- Irene Martínez Torres
- Juan Marín
- Maria Jose Marti
- Juan Carlos Martínez-Castrillo
- Carlota Méndez-del-Barrio
- Manuel Menéndez González
- Marina Mata
- Adolfo Mínguez
- Pablo Mir
- Elisabet Mondragon Rezola
- Esteban Muñoz
- Javier Pagonabarraga
- Pau Pastor
- Francisco Perez Errazquin
- Teresa Periñán-Tocino
- Javier Ruiz-Martínez
- Clara Ruz
- Antonio Sanchez Rodriguez
- María Sierra
- Esther Suarez-Sanmartin
- Cesar Tabernero
- Juan Pablo Tartari
- Cristina Tejera-Parrado
- Eduard Tolosa
- Francesc Valldeoriola
- Laura Vargas-González
- Lydia Vela
- Francisco Vives
- Alexander Zimprich
- Lasse Pihlstrom
- Mathias Toft
- Pille Taba
- Sulev Koks
- Sharon Hassin-Baer
- Kari Majamaa
- Ari Siitonen
- Pentti Tienari
- Njideka U. Okubadejo
- Oluwadamilola O. Ojo
- Rauan Kaiyrzhanov
- Chingiz Shashkin
- Nazira Zharkinbekova
- Vadim Akhmetzhanov
- Gulnaz Kaishybayeva
- Altynay Karimova
- Talgat Khaibullin
- Timothy L. Lynch
Enabling scientific discoveries that improve human health