Investigation of Autosomal Genetic Sex Differences in Parkinson's Disease
Por:
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
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:
Blauwendraat, C:
NIH, Lab Neurogenet, NIA, Bldg 35,35 Convent Dr, Bethesda, MD 20892 USA
Iwaki, H:
NIH, Lab Neurogenet, NIA, Bldg 35,35 Convent Dr, Bethesda, MD 20892 USA
NIH, Ctr Alzheimers & Related Dementias, Bethesda, MD 20892 USA
Data Tecn Int, Glen Echo, MD USA
Makarious, MB:
NIH, Lab Neurogenet, NIA, Bldg 35,35 Convent Dr, Bethesda, MD 20892 USA
UCL Queen Sq Inst Neurol, Dept Clin & Movement Neurosci, London, England
Bandres-Ciga, S:
NIH, Lab Neurogenet, NIA, Bldg 35,35 Convent Dr, Bethesda, MD 20892 USA
Leonard, HL:
NIH, Lab Neurogenet, NIA, Bldg 35,35 Convent Dr, Bethesda, MD 20892 USA
NIH, Ctr Alzheimers & Related Dementias, Bethesda, MD 20892 USA
Data Tecn Int, Glen Echo, MD USA
Grenn, FP:
NIH, Lab Neurogenet, NIA, Bldg 35,35 Convent Dr, Bethesda, MD 20892 USA
Lake, J:
NIH, Lab Neurogenet, NIA, Bldg 35,35 Convent Dr, Bethesda, MD 20892 USA
Krohn, L:
McGill Univ, Dept Human Genet, Montreal, PQ, Canada
McGill Univ, Neuro Montreal Neurol Inst Hosp, Montreal, PQ, Canada
Tan, M:
UCL Queen Sq Inst Neurol, Dept Clin & Movement Neurosci, London, England
Oslo Univ Hosp, Dept Neurol, Oslo, Norway
Kim, JJ:
NIH, Lab Neurogenet, NIA, Bldg 35,35 Convent Dr, Bethesda, MD 20892 USA
Queen Mary Univ London, Wolfson Inst Prevent Med, Prevent Neurol Unit, London, England
Gibbs, JR:
NIH, Lab Neurogenet, NIA, Bldg 35,35 Convent Dr, Bethesda, MD 20892 USA
Hernandez, DG:
NIH, Lab Neurogenet, NIA, Bldg 35,35 Convent Dr, Bethesda, MD 20892 USA
Ruskey, JA:
McGill Univ, Dept Human Genet, Montreal, PQ, Canada
McGill Univ, Neuro Montreal Neurol Inst Hosp, Montreal, PQ, Canada
Pihlstrom, L:
Oslo Univ Hosp, Dept Neurol, Oslo, Norway
Toft, M:
Oslo Univ Hosp, Dept Neurol, Oslo, Norway
van Hilten, JJ:
Leiden Univ, Med Ctr, Dept Neurol, Leiden, Netherlands
Marinus, J:
Leiden Univ, Med Ctr, Dept Neurol, Leiden, Netherlands
Schulte, C:
Univ Tubingen, Hertie Inst Clin Brain Res, Tubingen, Germany
German Ctr Neurodegenerat Dis DZNE, Tubingen, Germany
Brockmann, K:
Univ Tubingen, Hertie Inst Clin Brain Res, Tubingen, Germany
German Ctr Neurodegenerat Dis DZNE, Tubingen, Germany
Sharma, M:
Univ Tubingen, Inst Clin Epidemiol & Appl Biometry, Ctr Genet Epidemiol, Tubingen, Germany
Siitonen, A:
Univ Oulu, Res Unit Clin Neurosci, Oulu, Finland
Oulu Univ Hosp, Dept Neurol, Oulu, Finland
Oulu Univ Hosp, Med Res Ctr, Oulu, Finland
Majamaa, K:
Univ Oulu, Res Unit Clin Neurosci, Oulu, Finland
Oulu Univ Hosp, Dept Neurol, Oulu, Finland
Oulu Univ Hosp, Med Res Ctr, Oulu, Finland
Eerola-Rautio, J:
Helsinki Univ Hosp, Dept Neurol, Helsinki, Finland
Univ Helsinki, Biomedicum, Res Programs Unit, Mol Neurol, Helsinki, Finland
Tienari, PJ:
Helsinki Univ Hosp, Dept Neurol, Helsinki, Finland
Univ Helsinki, Biomedicum, Res Programs Unit, Mol Neurol, Helsinki, Finland
Grosset, DG:
Queen Elizabeth Univ Hosp, Inst Neurol Sci, Dept Neurol, Glasgow, Lanark, Scotland
Lesage, S:
Sorbonne Univ, AP HP, Paris Brain Inst Inst Cerveau ICM, INSERM,CNRS,Dept Neurol & Genet, Paris, France
Corvol, JC:
Sorbonne Univ, AP HP, Paris Brain Inst Inst Cerveau ICM, INSERM,CNRS,Dept Neurol & Genet, Paris, France
Brice, A:
Sorbonne Univ, AP HP, Paris Brain Inst Inst Cerveau ICM, INSERM,CNRS,Dept Neurol & Genet, Paris, France
Wood, N:
UCL Queen Sq Inst Neurol, Dept Clin & Movement Neurosci, London, England
Hardy, J:
UCL Queen Sq Inst Neurol, Dept Clin & Movement Neurosci, London, England
Gan-Or, Z:
McGill Univ, Dept Human Genet, Montreal, PQ, Canada
McGill Univ, Neuro Montreal Neurol Inst Hosp, Montreal, PQ, Canada
McGill Univ, Dept Neurol & Neurosurg, Montreal, PQ, Canada
Heutink, P:
Univ Tubingen, Hertie Inst Clin Brain Res, Tubingen, Germany
German Ctr Neurodegenerat Dis DZNE, Tubingen, Germany
Gasser, T:
Univ Tubingen, Hertie Inst Clin Brain Res, Tubingen, Germany
German Ctr Neurodegenerat Dis DZNE, Tubingen, Germany
Morris, HR:
UCL Queen Sq Inst Neurol, Dept Clin & Movement Neurosci, London, England
Noyce, AJ:
UCL Queen Sq Inst Neurol, Dept Clin & Movement Neurosci, London, England
Queen Mary Univ London, Wolfson Inst Prevent Med, Prevent Neurol Unit, London, England
Nalls, MA:
NIH, Lab Neurogenet, NIA, Bldg 35,35 Convent Dr, Bethesda, MD 20892 USA
NIH, Ctr Alzheimers & Related Dementias, Bethesda, MD 20892 USA
Data Tecn Int, Glen Echo, MD USA
Singleton, AB:
NIH, Lab Neurogenet, NIA, Bldg 35,35 Convent Dr, Bethesda, MD 20892 USA
NIH, Ctr Alzheimers & Related Dementias, Bethesda, MD 20892 USA
Clarimón J.:
Institut d’Investigació Biomèdica Sant Pau (IIB SANT PAU), Sant Quintí 77-79, 08041 Barcelona, Spain
Dols-Icardo, O:
Institut d’Investigació Biomèdica Sant Pau (IIB SANT PAU), Sant Quintí 77-79, 08041 Barcelona, Spain
Kulisevsky J.:
Institut d’Investigació Biomèdica Sant Pau (IIB SANT PAU), Sant Quintí 77-79, 08041 Barcelona, Spain
Pagonabarraga, J:
Institut d’Investigació Biomèdica Sant Pau (IIB SANT PAU), Sant Quintí 77-79, 08041 Barcelona, Spain
University College Dublin, Dublin, Ireland
Green Published, hybrid, Green Submitted
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