Investigation of Autosomal Genetic Sex Differences in Parkinson's Disease
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, ho...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2021 |
| País: | España |
| Institución: | Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau) |
| Repositorio: | r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau |
| OAI Identifier: | oai:iibsantpau.fundanetsuite.com:p7994 |
| Acceso en línea: | https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=7994 http://hdl.handle.net/10138/332389 |
| Access Level: | acceso abierto |
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Investigation of Autosomal Genetic Sex Differences in Parkinson's DiseaseBlauwendraat, CIwaki, HMakarious, MBBandres-Ciga, SLeonard, HLGrenn, FPLake, JKrohn, LTan, MKim, JJGibbs, JRHernandez, DGRuskey, JAPihlstrom, LToft, Mvan Hilten, JJMarinus, JSchulte, CBrockmann, KSharma, MSiitonen, AMajamaa, KEerola-Rautio, JTienari, PJGrosset, DGLesage, SCorvol, JCBrice, AWood, NHardy, JGan-Or, ZHeutink, PGasser, TMorris, HRNoyce, AJNalls, MASingleton, ABClarimón J.Dols-Icardo, OKulisevsky J.Pagonabarraga, JInt Parkinsons Dis Genomics ConsorObjective: 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.WILEY2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=7994http://hdl.handle.net/10138/332389ANNALS OF NEUROLOGYISSN: 03645134ISSNe: 15318249reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pauinstname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)Inglésinfo:eu-repo/semantics/openAccessoai:iibsantpau.fundanetsuite.com:p79942026-06-14T12:41:47Z |
| dc.title.none.fl_str_mv |
Investigation of Autosomal Genetic Sex Differences in Parkinson's Disease |
| title |
Investigation of Autosomal Genetic Sex Differences in Parkinson's Disease |
| spellingShingle |
Investigation of Autosomal Genetic Sex Differences in Parkinson's Disease Blauwendraat, C |
| title_short |
Investigation of Autosomal Genetic Sex Differences in Parkinson's Disease |
| title_full |
Investigation of Autosomal Genetic Sex Differences in Parkinson's Disease |
| title_fullStr |
Investigation of Autosomal Genetic Sex Differences in Parkinson's Disease |
| title_full_unstemmed |
Investigation of Autosomal Genetic Sex Differences in Parkinson's Disease |
| title_sort |
Investigation of Autosomal Genetic Sex Differences in Parkinson's Disease |
| dc.creator.none.fl_str_mv |
Blauwendraat, C Iwaki, H Makarious, MB Bandres-Ciga, S Leonard, HL Grenn, FP Lake, J Krohn, L Tan, M Kim, JJ Gibbs, JR Hernandez, DG Ruskey, JA Pihlstrom, L Toft, M van Hilten, JJ Marinus, J Schulte, C Brockmann, K Sharma, M Siitonen, A Majamaa, K Eerola-Rautio, J Tienari, PJ Grosset, DG Lesage, S Corvol, JC Brice, A Wood, N Hardy, J Gan-Or, Z Heutink, P Gasser, T Morris, HR Noyce, AJ Nalls, MA Singleton, AB Clarimón J. Dols-Icardo, O Kulisevsky J. Pagonabarraga, J Int Parkinsons Dis Genomics Consor |
| author |
Blauwendraat, C |
| author_facet |
Blauwendraat, C Iwaki, H Makarious, MB Bandres-Ciga, S Leonard, HL Grenn, FP Lake, J Krohn, L Tan, M Kim, JJ Gibbs, JR Hernandez, DG Ruskey, JA Pihlstrom, L Toft, M van Hilten, JJ Marinus, J Schulte, C Brockmann, K Sharma, M Siitonen, A Majamaa, K Eerola-Rautio, J Tienari, PJ Grosset, DG Lesage, S Corvol, JC Brice, A Wood, N Hardy, J Gan-Or, Z Heutink, P Gasser, T Morris, HR Noyce, AJ Nalls, MA Singleton, AB Clarimón J. Dols-Icardo, O Kulisevsky J. Pagonabarraga, J Int Parkinsons Dis Genomics Consor |
| author_role |
author |
| author2 |
Iwaki, H Makarious, MB Bandres-Ciga, S Leonard, HL Grenn, FP Lake, J Krohn, L Tan, M Kim, JJ Gibbs, JR Hernandez, DG Ruskey, JA Pihlstrom, L Toft, M van Hilten, JJ Marinus, J Schulte, C Brockmann, K Sharma, M Siitonen, A Majamaa, K Eerola-Rautio, J Tienari, PJ Grosset, DG Lesage, S Corvol, JC Brice, A Wood, N Hardy, J Gan-Or, Z Heutink, P Gasser, T Morris, HR Noyce, AJ Nalls, MA Singleton, AB Clarimón J. Dols-Icardo, O Kulisevsky J. Pagonabarraga, J Int Parkinsons Dis Genomics Consor |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| description |
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. |
| publishDate |
2021 |
| dc.date.none.fl_str_mv |
2021 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=7994 http://hdl.handle.net/10138/332389 |
| url |
https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=7994 http://hdl.handle.net/10138/332389 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess |
| eu_rights_str_mv |
openAccess |
| dc.publisher.none.fl_str_mv |
WILEY |
| publisher.none.fl_str_mv |
WILEY |
| dc.source.none.fl_str_mv |
ANNALS OF NEUROLOGY ISSN: 03645134 ISSNe: 15318249 reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau instname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau) |
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Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau) |
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r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau |
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r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau |
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15.811543 |