دورية أكاديمية
Characterizing the Genetic Architecture of Parkinson's Disease in Latinos.
العنوان: | Characterizing the Genetic Architecture of Parkinson's Disease in Latinos. |
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المؤلفون: | Loesch DP; Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD.; Program in Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, MD.; Department of Medicine, University of Maryland School of Medicine, Baltimore, MD., Horimoto ARVR; Department of Biostatistics, University of Washington, Seattle, WA., Heilbron K; 23andMe, Inc., Sunnyvale, CA., Sarihan EI; Lerner Research Institute, Genomic Medicine, Cleveland Clinic, Cleveland, OH., Inca-Martinez M; Lerner Research Institute, Genomic Medicine, Cleveland Clinic, Cleveland, OH., Mason E; Lerner Research Institute, Genomic Medicine, Cleveland Clinic, Cleveland, OH., Cornejo-Olivas M; Neurogenetics Research Center, Instituto Nacional de Ciencias Neurologicas, Lima, Peru.; Center for Global Health, Universidad Peruana Cayetano Heredia, Lima, Peru., Torres L; Movement Disorders Unit, Instituto Nacional de Ciencias Neurologicas, Lima, Peru.; School of Medicine, Universidad Nacional Mayor de San Marcos, Lima, Peru., Mazzetti P; Neurogenetics Research Center, Instituto Nacional de Ciencias Neurologicas, Lima, Peru.; School of Medicine, Universidad Nacional Mayor de San Marcos, Lima, Peru., Cosentino C; Movement Disorders Unit, Instituto Nacional de Ciencias Neurologicas, Lima, Peru.; School of Medicine, Universidad Nacional Mayor de San Marcos, Lima, Peru., Sarapura-Castro E; Neurogenetics Research Center, Instituto Nacional de Ciencias Neurologicas, Lima, Peru., Rivera-Valdivia A; Neurogenetics Research Center, Instituto Nacional de Ciencias Neurologicas, Lima, Peru., Medina AC; Universidad Nacional del Altiplano, Puno, Peru., Dieguez E; Neurology Institute, Universidad de la República, Montevideo, Uruguay., Raggio V; Department of Genetics, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay., Lescano A; Neurology Institute, Universidad de la República, Montevideo, Uruguay., Tumas V; Ribeirão Preto Medical School, Universidade de São Paulo, Ribeirão Preto, Brazil., Borges V; Movement Disorders Unit, Department of Neurology and Neurosurgery, Universidade Federal de São Paulo, São Paulo, Brazil., Ferraz HB; Movement Disorders Unit, Department of Neurology and Neurosurgery, Universidade Federal de São Paulo, São Paulo, Brazil., Rieder CR; Departamento de Neurologia, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil., Schumacher-Schuh A; Serviço de Neurologia, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.; Departamento de Farmacologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil., Santos-Lobato BL; Instituto de Ciências da Saúde, Universidade Federal do Pará, Belém, Brazil., Velez-Pardo C; Neuroscience Research Group, Medical Research Institute, Faculty of Medicine, Universidad de Antioquia (UdeA), Medellín, Colombia., Jimenez-Del-Rio M; Neuroscience Research Group, Medical Research Institute, Faculty of Medicine, Universidad de Antioquia (UdeA), Medellín, Colombia., Lopera F; Neuroscience Research Group, Medical Research Institute, Faculty of Medicine, Universidad de Antioquia (UdeA), Medellín, Colombia., Moreno S; Neuroscience Research Group, Medical Research Institute, Faculty of Medicine, Universidad de Antioquia (UdeA), Medellín, Colombia., Chana-Cuevas P; CETRAM, Facultad de ciencias Medicas, Universidad de Santiago de Chile, Santiago, Chile., Fernandez W; Neuroscience and Cell Death Research Groups, Medical School and Genetic Institute, Universidad Nacional de Colombia, Bogotá, Colombia., Arboleda G; Neuroscience and Cell Death Research Groups, Medical School and Genetic Institute, Universidad Nacional de Colombia, Bogotá, Colombia., Arboleda H; Neuroscience and Cell Death Research Groups, Medical School and Genetic Institute, Universidad Nacional de Colombia, Bogotá, Colombia., Arboleda-Bustos CE; Neuroscience and Cell Death Research Groups, Medical School and Genetic Institute, Universidad Nacional de Colombia, Bogotá, Colombia., Yearout D; Veterans Affairs Puget Sound Health Care System, Seattle, WA.; Department of Neurology, University of Washington, Seattle, WA., Zabetian CP; Veterans Affairs Puget Sound Health Care System, Seattle, WA.; Department of Neurology, University of Washington, Seattle, WA., Cannon P; 23andMe, Inc., Sunnyvale, CA., Thornton TA; Department of Biostatistics, University of Washington, Seattle, WA., O'Connor TD; Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD.; Program in Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, MD.; Department of Medicine, University of Maryland School of Medicine, Baltimore, MD., Mata IF; Lerner Research Institute, Genomic Medicine, Cleveland Clinic, Cleveland, OH.; Veterans Affairs Puget Sound Health Care System, Seattle, WA.; Department of Neurology, University of Washington, Seattle, WA. |
مؤلفون مشاركون: | 23andMe Research Team, Latin American Research Consortium on the Genetics of Parkinson's Disease (LARGE-PD) |
المصدر: | Annals of neurology [Ann Neurol] 2021 Sep; Vol. 90 (3), pp. 353-365. Date of Electronic Publication: 2021 Jul 22. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Wiley-Liss Country of Publication: United States NLM ID: 7707449 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1531-8249 (Electronic) Linking ISSN: 03645134 NLM ISO Abbreviation: Ann Neurol Subsets: MEDLINE |
أسماء مطبوعة: | Publication: New York, NY : Wiley-Liss Original Publication: Boston, Little, Brown. |
مواضيع طبية MeSH: | Genetic Loci/*genetics , Genetic Variation/*genetics , Genome-Wide Association Study/*methods , Hispanic or Latino/*genetics , Parkinson Disease/*ethnology , Parkinson Disease/*genetics, Adult ; Aged ; Cohort Studies ; Female ; Humans ; Male ; Middle Aged ; Parkinson Disease/diagnosis ; Polymorphism, Single Nucleotide/genetics ; South America/ethnology |
مستخلص: | Objective: This work was undertaken in order to identify Parkinson's disease (PD) risk variants in a Latino cohort, to describe the overlap in the genetic architecture of PD in Latinos compared to European-ancestry subjects, and to increase the diversity in PD genome-wide association (GWAS) data. Methods: We genotyped and imputed 1,497 PD cases and controls recruited from nine clinical sites across South America. We performed a GWAS using logistic mixed models; variants with a p-value <1 × 10 -5 were tested in a replication cohort of 1,234 self-reported Latino PD cases and 439,522 Latino controls from 23andMe, Inc. We also performed an admixture mapping analysis where local ancestry blocks were tested for association with PD status. Results: One locus, SNCA, achieved genome-wide significance (p-value <5 × 10 -8 ); rs356182 achieved genome-wide significance in both the discovery and the replication cohorts (discovery, G allele: 1.58 OR, 95% CI 1.35-1.86, p-value 2.48 × 10 -8 ; 23andMe, G allele: 1.26 OR, 95% CI 1.16-1.37, p-value 4.55 × 10 -8 ). In our admixture mapping analysis, a locus on chromosome 14, containing the gene STXBP6, achieved significance in a joint test of ancestries and in the Native American single-ancestry test (p-value <5 × 10 -5 ). A second locus on chromosome 6, containing the gene RPS6KA2, achieved significance in the African single-ancestry test (p-value <5 × 10 -5 ). Interpretation: This study demonstrated the importance of the SNCA locus for the etiology of PD in Latinos. By leveraging the demographic history of our cohort via admixture mapping, we identified two potential PD risk loci that merit further study. ANN NEUROL 2021;90:353-365. (© 2021 American Neurological Association.) |
التعليقات: | Comment in: Ann Neurol. 2021 Sep;90(3):350-352. (PMID: 34309075) Comment in: Mov Disord. 2021 Nov;36(11):2505. (PMID: 34476843) |
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معلومات مُعتمدة: | R35 HG010692 United States HG NHGRI NIH HHS; R01 NS112499 United States NS NINDS NIH HHS; R35HG010692 United States HG NHGRI NIH HHS; T32HL007698 United States HL NHLBI NIH HHS; T32 HL007698 United States HL NHLBI NIH HHS; 2020-31455 Universidad de Antioquia |
تواريخ الأحداث: | Date Created: 20210706 Date Completed: 20211108 Latest Revision: 20220902 |
رمز التحديث: | 20221213 |
مُعرف محوري في PubMed: | PMC8457043 |
DOI: | 10.1002/ana.26153 |
PMID: | 34227697 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1531-8249 |
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DOI: | 10.1002/ana.26153 |