Investigation of Autosomal Genetic Sex Differences in Parkinson's Disease.
Journal
Annals of neurology
ISSN: 1531-8249
Titre abrégé: Ann Neurol
Pays: United States
ID NLM: 7707449
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
revised:
24
04
2021
received:
19
01
2021
accepted:
24
04
2021
pubmed:
27
4
2021
medline:
15
9
2021
entrez:
26
4
2021
Statut:
ppublish
Résumé
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. 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. 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%). 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.
Identifiants
pubmed: 33901317
doi: 10.1002/ana.26090
pmc: PMC8422907
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
35-42Subventions
Organisme : Medical Research Council
ID : MR/K01417X/1
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : R01 CA141668
Pays : United States
Organisme : Medical Research Council
ID : G1001253
Pays : United Kingdom
Organisme : Intramural NIH HHS
ID : Z01 ES101986
Pays : United States
Organisme : German Federal Ministry of Education and Research
ID : 031A430A
Organisme : NIEHS NIH HHS
Pays : United States
Organisme : National Institutes of Health, Department of Health and Human Services
ID : Z01-AG000949-02
Organisme : Intramural NIH HHS
ID : Z01 AG000949
Pays : United States
Organisme : Parkinson's UK
ID : 8047
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/J004758/1
Pays : United Kingdom
Organisme : American Parkinson Disease Association (APDA)
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0701075
Pays : United Kingdom
Organisme : NIH HHS
ID : R01CA141668
Pays : United States
Organisme : Medical Research Council
ID : G1100643
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 076113
Pays : United Kingdom
Organisme : Department of Defense
ID : W81XWH-09-2-0128
Organisme : Wellcome Trust
ID : 090355
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L501542/1
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : K24 AG000949
Pays : United States
Organisme : NIH HHS
ID : R01NS037167
Pays : United States
Organisme : Parkinson's UK
ID : G-0907
Pays : United Kingdom
Organisme : German Federal Ministry of Education and Research
ID : 01ED1406
Organisme : Medical Research Council
ID : MR/N026004/1
Pays : United Kingdom
Organisme : Parkinson's UK
ID : G-1307
Pays : United Kingdom
Organisme : NINDS NIH HHS
ID : R01 NS037167
Pays : United States
Organisme : Parkinson's UK
ID : J-0804
Pays : United Kingdom
Organisme : Barnes Jewish Hospital Foundation; Greater St Louis Chapter of the APDA
Organisme : National Institutes of Health, Department of Health and Human Services
ID : Z01-ES101986
Organisme : National Institute of Neurological Disorders and Stroke (NINDS)
Organisme : Wellcome Trust
ID : 085475
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0901254
Pays : United Kingdom
Organisme : National Institute on Aging (NIA)
Organisme : NIH HHS
ID : P50NS071674
Pays : United States
Organisme : Medical Research Council
ID : G0700943
Pays : United Kingdom
Organisme : National Institutes of Health, Department of Health and Human Services
ID : 1ZIA-NS003154
Organisme : NINDS NIH HHS
ID : P50 NS071674
Pays : United States
Investigateurs
Alastair J Noyce
(AJ)
Rauan Kaiyrzhanov
(R)
Ben Middlehurst
(B)
Demis A Kia
(DA)
Manuela Tan
(M)
Henry Houlden
(H)
Catherine S Storm
(CS)
Huw R Morris
(HR)
Helene Plun-Favreau
(H)
Peter Holmans
(P)
John Hardy
(J)
Daniah Trabzuni
(D)
John Quinn
(J)
Vivien Bubb
(V)
Kin Y Mok
(KY)
Kerri J Kinghorn
(KJ)
Nicholas W Wood
(NW)
Patrick Lewis
(P)
Sebastian R Schreglmann
(SR)
Ruth Lovering
(R)
Lea R'Bibo
(L)
Claudia Manzoni
(C)
Mie Rizig
(M)
Mina Ryten
(M)
Sebastian Guelfi
(S)
Valentina Escott-Price
(V)
Viorica Chelban
(V)
Thomas Foltynie
(T)
Nigel Williams
(N)
Karen E Morrison
(KE)
Carl Clarke
(C)
Kirsten Harvey
(K)
Benjamin M Jacobs
(BM)
Alexis Brice
(A)
Fabrice Danjou
(F)
Suzanne Lesage
(S)
Jean-Christophe Corvol
(JC)
Maria Martinez
(M)
Claudia Schulte
(C)
Kathrin Brockmann
(K)
Javier Simón-Sánchez
(J)
Peter Heutink
(P)
Patrizia Rizzu
(P)
Manu Sharma
(M)
Thomas Gasser
(T)
Susanne A Schneider
(SA)
Mark R Cookson
(MR)
Sara Bandres-Ciga
(S)
Cornelis Blauwendraat
(C)
David W Craig
(DW)
Kimberley Billingsley
(K)
Mary B Makarious
(MB)
Derek P Narendra
(DP)
Faraz Faghri
(F)
J Raphael Gibbs
(JR)
Dena G Hernandez
(DG)
Kendall Van Keuren-Jensen
(K)
Joshua M Shulman
(JM)
Hirotaka Iwaki
(H)
Hampton L Leonard
(HL)
Mike A Nalls
(MA)
Laurie Robak
(L)
Jose Bras
(J)
Rita Guerreiro
(R)
Steven Lubbe
(S)
Timothy Troycoco
(T)
Steven Finkbeiner
(S)
Niccolo E Mencacci
(NE)
Codrin Lungu
(C)
Andrew B Singleton
(AB)
Sonja W Scholz
(SW)
Xylena Reed
(X)
Ryan J Uitti
(RJ)
Owen A Ross
(OA)
Francis P Grenn
(FP)
Anni Moore
(A)
Roy N Alcalay
(RN)
Zbigniew K Wszolek
(ZK)
Ziv Gan-Or
(Z)
Guy A Rouleau
(GA)
Lynne Krohn
(L)
Kheireddin Mufti
(K)
Jacobus J van Hilten
(JJ)
Johan Marinus
(J)
Astrid D Adarmes-Gómez
(AD)
Miquel Aguilar
(M)
Ignacio Alvarez
(I)
Victoria Alvarez
(V)
Francisco Javier Barrero
(FJ)
Jesús Alberto Bergareche Yarza
(JAB)
Inmaculada Bernal-Bernal
(I)
Marta Blazquez
(M)
Marta Bonilla-Toribio
(M)
Juan A Botía
(JA)
María Teresa Boungiorno
(MT)
Dolores Buiza-Rueda
(D)
Ana Cámara
(A)
Fátima Carrillo
(F)
Mario Carrión-Claro
(M)
Debora Cerdan
(D)
Jordi Clarimón
(J)
Yaroslau Compta
(Y)
Monica Diez-Fairen
(M)
Oriol Dols-Icardo
(O)
Jacinto Duarte
(J)
Raquel Duran
(R)
Francisco Escamilla-Sevilla
(F)
Mario Ezquerra
(M)
Cici Feliz
(C)
Manel Fernández
(M)
Rubén Fernández-Santiago
(R)
Ciara Garcia
(C)
Pedro García-Ruiz
(P)
Pilar Gómez-Garre
(P)
Maria Jose Gomez Heredia
(MJG)
Isabel Gonzalez-Aramburu
(I)
Ana Gorostidi Pagola
(AG)
Janet Hoenicka
(J)
Jon Infante
(J)
Silvia Jesús
(S)
Adriano Jimenez-Escrig
(A)
Jaime Kulisevsky
(J)
Miguel A Labrador-Espinosa
(MA)
Jose Luis Lopez-Sendon
(JL)
Adolfo López de Munain Arregui
(AL)
Daniel Macias
(D)
Irene Martínez Torres
(IM)
Juan Marín
(J)
Maria Jose Marti
(MJ)
Juan Carlos Martínez-Castrillo
(JC)
Carlota Méndez-Del-Barrio
(C)
Manuel Menéndez González
(MM)
Marina Mata
(M)
Adolfo Mínguez
(A)
Pablo Mir
(P)
Elisabet Mondragon Rezola
(EM)
Esteban Muñoz
(E)
Javier Pagonabarraga
(J)
Pau Pastor
(P)
Francisco Perez Errazquin
(FP)
Teresa Periñán-Tocino
(T)
Javier Ruiz-Martínez
(J)
Clara Ruz
(C)
Antonio Sanchez Rodriguez
(AS)
María Sierra
(M)
Esther Suarez-Sanmartin
(E)
Cesar Tabernero
(C)
Juan Pablo Tartari
(JP)
Cristina Tejera-Parrado
(C)
Eduard Tolosa
(E)
Francesc Valldeoriola
(F)
Laura Vargas-González
(L)
Lydia Vela
(L)
Francisco Vives
(F)
Alexander Zimprich
(A)
Lasse Pihlstrom
(L)
Mathias Toft
(M)
Pille Taba
(P)
Sulev Koks
(S)
Sharon Hassin-Baer
(S)
Kari Majamaa
(K)
Ari Siitonen
(A)
Pentti Tienari
(P)
Njideka U Okubadejo
(NU)
Oluwadamilola O Ojo
(OO)
Rauan Kaiyrzhanov
(R)
Chingiz Shashkin
(C)
Nazira Zharkinbekova
(N)
Vadim Akhmetzhanov
(V)
Gulnaz Kaishybayeva
(G)
Altynay Karimova
(A)
Talgat Khaibullin
(T)
Timothy L Lynch
(TL)
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2021 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association. This article has been contributed to by US Government employees and their work is in the public domain in the USA.
Références
Mov Disord. 2000 Jul;15(4):669-77
pubmed: 10928577
Neurology. 1988 Sep;38(9):1402-6
pubmed: 3412587
Nat Genet. 2016 Oct;48(10):1279-83
pubmed: 27548312
Nat Genet. 2015 Mar;47(3):291-5
pubmed: 25642630
Lancet Neurol. 2019 Dec;18(12):1091-1102
pubmed: 31701892
Mov Disord. 2020 Nov;35(11):2056-2067
pubmed: 32864809
Brain. 2020 Jul 1;143(7):2272-2280
pubmed: 32591829
J Parkinsons Dis. 2021;11(4):1981-1993
pubmed: 34275906
Nature. 2018 Oct;562(7726):203-209
pubmed: 30305743
PLoS Med. 2015 Mar 31;12(3):e1001779
pubmed: 25826379
Nat Genet. 2017 Mar;49(3):325-331
pubmed: 28092683
Neurology. 2016 Feb 9;86(6):520-6
pubmed: 26764029
Brain. 2019 Mar 1;142(3):744-759
pubmed: 30789229
Ann Neurol. 2021 Jul;90(1):22-34
pubmed: 33583074
Mov Disord. 2019 Jun;34(6):866-875
pubmed: 30957308
Nat Genet. 2016 Oct;48(10):1284-1287
pubmed: 27571263
Dialogues Clin Neurosci. 2016 Dec;18(4):437-446
pubmed: 28179815
Gigascience. 2015 Feb 25;4:7
pubmed: 25722852
Bioinformatics. 2017 Sep 01;33(17):2776-2778
pubmed: 28475694
Nat Commun. 2013;4:2771
pubmed: 24264146
Proc Natl Acad Sci U S A. 2019 Aug 13;116(33):16577-16582
pubmed: 31371505
J Neurol Neurosurg Psychiatry. 2016 Sep;87(9):952-7
pubmed: 26701996
Am J Epidemiol. 2004 Nov 15;160(10):977-84
pubmed: 15522854
Mov Disord. 2021 Jan;36(1):106-117
pubmed: 33002231
Am J Hum Genet. 2011 Jan 7;88(1):76-82
pubmed: 21167468
Mov Disord. 2015 Oct;30(12):1591-601
pubmed: 26474316
Lancet Neurol. 2020 Feb;19(2):170-178
pubmed: 31521533
J Neurol Neurosurg Psychiatry. 2007 Aug;78(8):905-6
pubmed: 17635983
Bioinformatics. 2016 May 1;32(9):1423-6
pubmed: 27153000
Int J Environ Res Public Health. 2016 Sep 03;13(9):
pubmed: 27598189
Science. 2020 Sep 11;369(6509):
pubmed: 32913072
Bioinformatics. 2010 Sep 1;26(17):2190-1
pubmed: 20616382
PLoS Genet. 2011 Jun;7(6):e1002142
pubmed: 21738488
JAMA Neurol. 2020 Jun 1;77(6):746-754
pubmed: 32310270