Investigation of Autosomal Genetic Sex Differences in Parkinson's Disease
Por:
Leonard H, Lake J, Kim JJ, Gibbs JR, Ruskey JA, Pihlstrøm L, Eerola-Rautio J, Tienari PJ, Grosset DG, Wood N, Noyce AJ, Middlehurst B, Kia DA, Tan M, Houlden H, Storm CS, Morris HR, Plun-Favreau H, Holmans P, Hardy J, Trabzuni D, Quinn J, Bubb V, Mok KY, Kinghorn KJ, Wood NW, Lewis P, Schreglmann SR, Lovering R, R'Bibo L, Manzoni C, Rizig M, Ryten M, Guelfi S, Escott-Price V, Chelban V, Foltynie T, Williams N, Morrison KE, Clarke C, Harvey K, Jacobs BM, Brice A, Danjou F, Lesage S, Corvol JC, Martinez M, Schulte C, Brockmann K, Simón-Sánchez J, Heutink P, Rizzu P, Sharma M, Gasser T, Schneider SA, Cookson MR, Bandres-Ciga S, Blauwendraat C, Craig DW, Billingsley K, Makarious MB, Narendra DP, Faghri F, Gibbs JR, Hernandez DG, Van Keuren-Jensen K, Shulman JM, Iwaki H, Leonard HL, Nalls MA, Robak L, Bras J, Guerreiro R, Lubbe S, Troycoco T, Finkbeiner S, Mencacci NE, Lungu C, Singleton AB, Scholz SW, Reed X, Uitti RJ, Ross OA, Grenn FP, Moore A, Alcalay RN, Wszolek ZK, Gan-Or Z, Rouleau GA, Krohn L, Mufti K, van Hilten JJ, Marinus J, Adarmes-Gómez AD, Aguilar M, Alvarez I, Alvarez V, Barrero FJ, Yarza JAB, Bernal-Bernal I, Blazquez M, Bonilla-Toribio M, Botía JA, Boungiorno MT, Buiza-Rueda D, Cámara A, Carrillo F, Carrión-Claro M, Cerdan D, Clarimón J, Compta Y, Diez-Fairen M, Dols-Icardo O, Duarte J, Duran R, Escamilla-Sevilla F, Ezquerra M, Feliz C, Fernández M, Fernández-Santiago R, Garcia C, García-Ruiz P, Gómez-Garre P, Heredia MJG, Gonzalez-Aramburu I, Pagola AG, Hoenicka J, Infante J, Jesús S, Jimenez-Escrig A, Kulisevsky J, Labrador-Espinosa MA, Lopez-Sendon JL, de Munain Arregui AL, Macias D, Torres IM, Marín J, Marti MJ, Martínez-Castrillo JC, Méndez-Del-Barrio C, González MM, Mata M, Mínguez A, Mir P, Rezola EM, Muñoz E, Pagonabarraga J, Pastor P, Errazquin FP, Periñán-Tocino T, Ruiz-Martínez J, Ruz C, Rodriguez AS, Sierra M, Suarez-Sanmartin E, Tabernero C, Tartari JP, Tejera-Parrado C, Tolosa E, Valldeoriola F, Vargas-González L, Vela L, Vives F, Zimprich A, Pihlstrom L, Toft M, Taba P, Koks S, Hassin-Baer S, Majamaa K, Siitonen A, Tienari P, Okubadejo NU, Ojo OO, Kaiyrzhanov R, Shashkin C, Zharkinbekova N, Akhmetzhanov V, Kaishybayeva G, Karimova A, Khaibullin T, Lynch TL and International Parkinson's Disease Genomics Consortium (IPDGC)
Publicada:
1 jul 2021
Ahead of Print:
1 may 2021
Resumen:
Objective: Parkinson's disease (PD) is a complex neurodegenerative disorder. Men are on average similar to 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 (similar to 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.
Filiaciones:
Leonard H:
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA
Center for Alzheimer's and Related Dementias, National Institutes of Health, Bethesda, Maryland, USA, 20892
Data Tecnica International, Glen Echo, Maryland, USA
Lake J:
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA
Kim JJ:
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA
Gibbs JR:
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA
Ruskey JA:
Department of Human Genetics, McGill University, Montreal, Quebec, Canada
The Neuro (Montreal Neurological Institute-Hospital), McGill University, Montreal, Quebec, Canada
Pihlstrøm L:
Department of Neurology, Oslo University Hospital, Oslo, Norway
Eerola-Rautio J:
Department of Neurology, Helsinki University Hospital, and Molecular Neurology, Research Programs Unit, Biomedicum, University of Helsinki, Helsinki, Finland
Tienari PJ:
Department of Neurology, Helsinki University Hospital, and Molecular Neurology, Research Programs Unit, Biomedicum, University of Helsinki, Helsinki, Finland
Grosset DG:
Department of Neurology, Institute of Neurological Sciences, Queen Elizabeth University Hospital, Glasgow, Scotland, UK
Wood N:
Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK
Noyce AJ:
Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK
Preventive Neurology Unit, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK
Tan M:
Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK
Morris HR:
Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK
Hardy J:
Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK
Brice A:
Department of Neurology and Genetics, Sorbonne Université, Paris Brain Institute - ICM, Assistance Publique Hôpitaux de Paris, Inserm, CNRS, Paris, France
Lesage S:
Department of Neurology and Genetics, Sorbonne Université, Paris Brain Institute - ICM, Assistance Publique Hôpitaux de Paris, Inserm, CNRS, Paris, France
Corvol JC:
Department of Neurology and Genetics, Sorbonne Université, Paris Brain Institute - ICM, Assistance Publique Hôpitaux de Paris, Inserm, CNRS, Paris, France
Schulte C:
Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
German Center for Neurodegenerative Diseases (DZNE), Tuebingen, Germany
Brockmann K:
Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
German Center for Neurodegenerative Diseases (DZNE), Tuebingen, Germany
Heutink P:
German Center for Neurodegenerative Diseases (DZNE), Tuebingen, Germany
Centre for Genetic Epidemiology, Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany
Sharma M:
Centre for Genetic Epidemiology, Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany
Gasser T:
German Center for Neurodegenerative Diseases (DZNE), Tuebingen, Germany
Centre for Genetic Epidemiology, Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany
Bandres-Ciga S:
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA
Blauwendraat C:
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA
Makarious MB:
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA
Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK
Hernandez DG:
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA
Iwaki H:
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA
Center for Alzheimer's and Related Dementias, National Institutes of Health, Bethesda, Maryland, USA, 20892
Data Tecnica International, Glen Echo, Maryland, USA
Nalls MA:
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA
Center for Alzheimer's and Related Dementias, National Institutes of Health, Bethesda, Maryland, USA, 20892
Data Tecnica International, Glen Echo, Maryland, USA
Singleton AB:
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA
Data Tecnica International, Glen Echo, Maryland, USA
Grenn FP:
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA
Gan-Or Z:
Department of Human Genetics, McGill University, Montreal, Quebec, Canada
The Neuro (Montreal Neurological Institute-Hospital), McGill University, Montreal, Quebec, Canada
Department of Neurology & Neurosurgery, McGill University, Montreal, Quebec, Canada
Krohn L:
Department of Human Genetics, McGill University, Montreal, Quebec, Canada
The Neuro (Montreal Neurological Institute-Hospital), McGill University, Montreal, Quebec, Canada
van Hilten JJ:
Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands
Marinus J:
Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands
Toft M:
Department of Neurology, Oslo University Hospital, Oslo, Norway
Majamaa K:
Institute of Clinical Medicine, Department of Neurology, University of Oulu, Oulu, Finland
Department of Neurology and Medical Research Center, Oulu University Hospital, Oulu, Finland
Siitonen A:
Institute of Clinical Medicine, Department of Neurology, University of Oulu, Oulu, Finland
Department of Neurology and Medical Research Center, Oulu University Hospital, Oulu, Finland
Green Published, Green Submitted, hybrid
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