Investigation of Autosomal Genetic Sex Differences in Parkinson's Disease. Issue 1 (24th May 2021)

• Record Type: Journal Article
• Authors: Blauwendraat, Cornelis; Iwaki, Hirotaka; Makarious, Mary B.; Bandres‐Ciga, Sara; Leonard, Hampton L.; Grenn, Francis P.; Lake, Julie; Krohn, Lynne; Tan, Manuela; Kim, Jonggeol J.; Gibbs, Jesse R.; Hernandez, Dena G.; Ruskey, Jennifer A.; Pihlstrøm, Lasse; Toft, Mathias; van Hilten, Jacobus J.; Marinus, Johan; Schulte, Claudia; Brockmann, Kathrin; Sharma, Manu; Siitonen, Ari; Majamaa, Kari; Eerola‐Rautio, Johanna; Tienari, Pentti J.; Grosset, Donald G.; Lesage, Suzanne; Corvol, Jean‐Christophe; Brice, Alexis; Wood, Nick; Hardy, John; Gan‐Or, Ziv; Heutink, Peter; Gasser, Thomas; Morris, Huw R.; Noyce, Alastair J.; Nalls, Mike A.; Singleton, Andrew B.;
• Other Names: Noyce Alastair J. investigator.; Kaiyrzhanov Rauan investigator.; Middlehurst Ben investigator.; Kia Demis A. investigator.; Tan Manuela investigator.; Houlden Henry investigator.; Storm Catherine S. investigator.; Morris Huw R. investigator.; Plun‐Favreau Helene investigator.; Holmans Peter investigator.; Hardy John investigator.; Trabzuni Daniah investigator.; Quinn John investigator.; Bubb Vivien investigator.; Mok Kin Y. investigator.; Kinghorn Kerri J. investigator.; Wood Nicholas W. investigator.; Lewis Patrick investigator.; Schreglmann Sebastian R. investigator.; Lovering Ruth investigator.; R'Bibo Lea investigator.; Manzoni Claudia investigator.; Rizig Mie investigator.; Ryten Mina investigator.; Guelfi Sebastian investigator.; Escott‐Price Valentina investigator.; Chelban Viorica investigator.; Foltynie Thomas investigator.; Williams Nigel investigator.; Morrison Karen E. investigator.; Clarke Carl investigator.; Harvey Kirsten investigator.; Jacobs Benjamin M. investigator.; Brice Alexis investigator.; Danjou Fabrice investigator.; Lesage Suzanne investigator.; Corvol Jean‐Christophe investigator.; Martinez Maria investigator.; Schulte Claudia investigator.; Brockmann Kathrin investigator.; Simón‐Sánchez Javier investigator.; Heutink Peter investigator.; Rizzu Patrizia investigator.; Sharma Manu investigator.; Gasser Thomas investigator.; Schneider Susanne A. investigator.; Cookson Mark R. investigator.; Bandres‐Ciga Sara investigator.; Blauwendraat Cornelis investigator.; Craig David W. investigator.; Billingsley Kimberley investigator.; Makarious Mary B. investigator.; Narendra Derek P. investigator.; Faghri Faraz investigator.; Gibbs J. Raphael investigator.; Hernandez Dena G. investigator.; Van Keuren‐Jensen Kendall investigator.; Shulman Joshua M. investigator.; Iwaki Hirotaka investigator.; Leonard Hampton L. investigator.; Nalls Mike A. investigator.; Robak Laurie investigator.; Bras Jose investigator.; Guerreiro Rita investigator.; Lubbe Steven investigator.; Troycoco Timothy investigator.; Finkbeiner Steven investigator.; Mencacci Niccolo E. investigator.; Lungu Codrin investigator.; Singleton Andrew B. investigator.; Scholz Sonja W. investigator.; Reed Xylena investigator.; Uitti Ryan J. investigator.; Ross Owen A. investigator.; Grenn Francis P. investigator.; Moore Anni investigator.; Alcalay Roy N. investigator.; Wszolek Zbigniew K. investigator.; Gan‐Or Ziv investigator.; Rouleau Guy A. investigator.; Krohn Lynne investigator.; Mufti Kheireddin investigator.; van Hilten Jacobus J. investigator.; Marinus Johan investigator.; Adarmes‐Gómez Astrid D. investigator.; Aguilar Miquel investigator.; Alvarez Ignacio investigator.; Alvarez Victoria investigator.; Barrero Francisco Javier investigator.; Yarza Jesús Alberto Bergareche investigator.; Bernal‐Bernal Inmaculada investigator.; Blazquez Marta investigator.; Bonilla‐Toribio Marta investigator.; Botía Juan A. investigator.; Boungiorno María Teresa investigator.; Buiza‐Rueda Dolores investigator.; Cámara Ana investigator.; Carrillo Fátima investigator.; Carrión‐Claro Mario investigator.; Cerdan Debora investigator.; Clarimón Jordi investigator.; Compta Yaroslau investigator.; Diez‐Fairen Monica investigator.; Dols‐Icardo Oriol investigator.; Duarte Jacinto investigator.; Duran Raquel investigator.; Escamilla‐Sevilla Francisco investigator.; Ezquerra Mario investigator.; Feliz Cici investigator.; Fernández Manel investigator.; Fernández‐Santiago Rubén investigator.; Garcia Ciara investigator.; García‐Ruiz Pedro investigator.; Gómez‐Garre Pilar investigator.; Heredia Maria Jose Gomez investigator.; Gonzalez‐Aramburu Isabel investigator.; Pagola Ana Gorostidi investigator.; Hoenicka Janet investigator.; Infante Jon investigator.; Jesús Silvia investigator.; Jimenez‐Escrig Adriano investigator.; Kulisevsky Jaime investigator.; Labrador‐Espinosa Miguel A. investigator.; Lopez‐Sendon Jose Luis investigator.; de Munain Arregui Adolfo López investigator.; Macias Daniel investigator.; Torres Irene Martínez investigator.; Marín Juan investigator.; Marti Maria Jose investigator.; Martínez‐Castrillo Juan Carlos investigator.; Méndez‐del‐Barrio Carlota investigator.; González Manuel Menéndez investigator.; Mata Marina investigator.; Mínguez Adolfo investigator.; Mir Pablo investigator.; Rezola Elisabet Mondragon investigator.; Muñoz Esteban investigator.; Pagonabarraga Javier investigator.; Pastor Pau investigator.; Errazquin Francisco Perez investigator.; Periñán‐Tocino Teresa investigator.; Ruiz‐Martínez Javier investigator.; Ruz Clara investigator.; Rodriguez Antonio Sanchez investigator.; Sierra María investigator.; Suarez‐Sanmartin Esther investigator.; Tabernero Cesar investigator.; Tartari Juan Pablo investigator.; Tejera‐Parrado Cristina investigator.; Tolosa Eduard investigator.; Valldeoriola Francesc investigator.; Vargas‐González Laura investigator.; Vela Lydia investigator.; Vives Francisco investigator.; Zimprich Alexander investigator.; Pihlstrom Lasse investigator.; Toft Mathias investigator.; Taba Pille investigator.; Koks Sulev investigator.; Hassin‐Baer Sharon investigator.; Majamaa Kari investigator.; Siitonen Ari investigator.; Tienari Pentti investigator.; Okubadejo Njideka U. investigator.; Ojo Oluwadamilola O. investigator.; Kaiyrzhanov Rauan investigator.; Shashkin Chingiz investigator.; Zharkinbekova Nazira investigator.; Akhmetzhanov Vadim investigator.; Kaishybayeva Gulnaz investigator.; Karimova Altynay investigator.; Khaibullin Talgat investigator.; Lynch Timothy L. investigator.;
• Is Part Of: Annals of neurology. Volume 90:Issue 1(2021)
• Page Start: 35
• Page End: 42
• Publication Date: 2021-05-24
• Subjects: Neurology -- Periodicals; Pediatric neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; 616.8
• DOI: 10.1002/ana.26090
• Languages: English
• ISSNs: 0364-5134

Abstract

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