دورية أكاديمية
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Polygenic risk prediction and SNCA haplotype analysis in a Latino Parkinson's disease cohort.

التفاصيل البيبلوغرافية
العنوان: Polygenic risk prediction and SNCA haplotype analysis in a Latino Parkinson's disease cohort.
المؤلفون: Loesch DP; Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA; Program in Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, MD, USA; Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA., Horimoto ARVR; Department of Biostatistics, University of Washington, Seattle, WA, USA., Sarihan EI; Lerner Research Institute, Genomic Medicine, Cleveland Clinic, Cleveland, OH, USA., Inca-Martinez M; Lerner Research Institute, Genomic Medicine, Cleveland Clinic, Cleveland, OH, USA., Mason E; Lerner Research Institute, Genomic Medicine, Cleveland Clinic, Cleveland, OH, USA., 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; Department of Genetics, Facultad de Medicina, 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, 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, Antioquia, Colombia., Jimenez-Del-Rio M; Neuroscience Research Group, Medical Research Institute, Faculty of Medicine, Universidad de Antioquia (UdeA), Medellín, Antioquia, Colombia., Lopera F; Neuroscience Research Group, Medical Research Institute, Faculty of Medicine, Universidad de Antioquia (UdeA), Medellín, Antioquia, Colombia., Moreno S; Neuroscience Research Group, Medical Research Institute, Faculty of Medicine, Universidad de Antioquia (UdeA), Medellín, Antioquia, Colombia., Chana-Cuevas P; CETRAM, Facultad de ciencias Medicas, Universidad de Santiago de Chile, 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, USA; Department of Neurology, University of Washington, Seattle, WA, USA., Zabetian CP; Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA; Department of Neurology, University of Washington, Seattle, WA, USA., Thornton TA; Department of Biostatistics, University of Washington, Seattle, WA, USA., Mata IF; Lerner Research Institute, Genomic Medicine, Cleveland Clinic, Cleveland, OH, USA; Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA; Department of Neurology, University of Washington, Seattle, WA, USA. Electronic address: matai@ccf.org., O'Connor TD; Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA; Program in Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, MD, USA; Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA. Electronic address: timothydoconnor@gmail.com.
مؤلفون مشاركون: International Parkinson Disease Genomics Consortium (IPDGC), Latin American Research Consortium on the Genetics of Parkinson's Disease (LARGE-PD)
المصدر: Parkinsonism & related disorders [Parkinsonism Relat Disord] 2022 Sep; Vol. 102, pp. 7-15. Date of Electronic Publication: 2022 Jun 18.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: Elsevier Science Country of Publication: England NLM ID: 9513583 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-5126 (Electronic) Linking ISSN: 13538020 NLM ISO Abbreviation: Parkinsonism Relat Disord Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Kidlington, Oxford, U.K. ; Tarrytown, NY : Elsevier Science, c1995-
مواضيع طبية MeSH: Genome-Wide Association Study* , Parkinson Disease*/genetics, Genetic Predisposition to Disease/genetics ; Haplotypes ; Hispanic or Latino/genetics ; Humans ; Polymorphism, Single Nucleotide/genetics ; Risk Factors ; alpha-Synuclein/genetics
مستخلص: Background: Large-scale Parkinson's disease (PD) genome-wide association studies (GWAS) have, until recently, only been conducted on subjects with European-ancestry. Consequently, polygenic risk scores (PRS) constructed using PD GWAS data are likely to be less predictive when applied to non-European cohorts.
Methods: Using GWAS data from the largest study to date, we constructed a PD PRS for a Latino PD cohort (1497 subjects from LARGE-PD) and tested it for association with PD status and age at onset. We validated the PRS performance by testing it in an independent Latino cohort (448 subjects) and by repeating the analysis in LARGE-PD with the addition of 440 external Peruvian controls. We also tested SNCA haplotypes for association with PD risk in LARGE-PD and a European-ancestry PD cohort.
Results: The GWAS-significant PD PRS had an area under the receiver-operator curve (AUC) of 0.668 (95% CI: 0.640-0.695) in LARGE-PD. The inclusion of external Peruvian controls mitigated this result, dropping the AUC 0.632 (95% CI: 0.607-0.657). At the SNCA locus, haplotypes differ by ancestry. Ancestry-specific SNCA haplotypes were associated with PD status in both LARGE-PD and the European-ancestry cohort (p-value < 0.05). These haplotypes both include the rs356182 G-allele, but only share 14% of their variants overall.
Conclusion: The PD PRS has potential for PD risk prediction in Latinos, but variability caused by admixture patterns and bias in a European-ancestry PD PRS data limits its utility. The inclusion of diverse subjects can help elucidate PD risk loci and improve risk prediction in non-European cohorts.
Competing Interests: Declaration of competing interests The authors declare no competing interests.
(Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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معلومات مُعتمدة: D43 TW009345 United States TW FIC NIH HHS; R01 NS112499 United States NS NINDS NIH HHS; R35 HG010692 United States HG NHGRI NIH HHS; T32 HL007698 United States HL NHLBI NIH HHS
المشرفين على المادة: 0 (SNCA protein, human)
0 (alpha-Synuclein)
تواريخ الأحداث: Date Created: 20220802 Date Completed: 20220928 Latest Revision: 20231102
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC10112543
DOI: 10.1016/j.parkreldis.2022.06.010
PMID: 35917738
قاعدة البيانات: MEDLINE
الوصف
تدمد:1873-5126
DOI:10.1016/j.parkreldis.2022.06.010