Autor(es)
Afiliação
Resumo em Inglês
Background:Sex differences inParkinson’s disease (PD) risk are well-known. How-ever, the role of sex chromosomes in the developmentand progression of PD is still unclear.Objective:The objective of this study was to perform thefirst X-chromosome–wide association study for PD risk ina Latin American cohort.Methods:We used data from three admixed cohorts:(1) Latin American Research consortium on the Genetics ofParkinson’s Disease (n=1504) as discover cohort, and(2) Latino cohort from International Parkinson DiseaseGenomics Consortium (n=155)and(3)BambuiAgingcohort (n=1442) as replication cohorts. We also devel-oped an X-chromosome framework specifically designedfor admixed populations.Results:We identified eight linkage disequilibrium regionsassociated with PD. We replicated one of these regions (topvariant rs525496; discovery odds ratio [95% confidenceinterval]: 0.60 [0.478–0.77],P=3.1310 5replicationodds ratio: 0.60 [0.37–0.98],P=0.04). rs5525496 is associ-ated with multiple expression quantitative trait loci in brainand non-brain tissues, includingRAB9B,H2BFM,TSMB15B,andGLRA4, but colocalization analysis suggeststhat rs5525496 may not mediate risk by expression of thesegenes. We also replicated a previous X-chromosome–wideassociation studyfinding (rs28602900), showing that thisvariant is associated with PD innon-European populations.Conclusions:Our results reinforce the importance ofincluding X-chromosome and diverse populations ingenetic studies. © 2023 The Authors.Movement Disor-derspublished by LLC on behalf ofInternational Parkinson and Movement Disorder Society.
Editor
Wiley Periodicals
Referência
LEAL, Thiago P. et al. X-Chromosome Association Study in Latin American Cohorts Identifies New Loci in Parkinson's Disease. Movement Disorders, 2023. doi.org/10.1002/mds.29508
ISSN
0885-3185
Notas
Shilpa C. Rao
The Parkinson’s Foundation. Miami, Florida, USA
Jennifer N. French-Kwawu
Institute for Genome Sciences. University of Maryland School of Medicine. Baltimore, Maryland, USA
Mateus H. Gouveia
Center for Research on Genomics and Global Health. National Human Genome Research Institute. National Institutes of Health. Bethesda,Maryland, USA
Victor Borda
Institute for Genome Sciences. University of Maryland School of Medicine. Baltimore, Maryland, USA
Sara Bandres-Ciga
Center for Alzheimer’s and Related Dementias. National Institutes of Health. Bethesda, Maryland, USA
Miguel Inca-Martinez
Lerner Research Institute. Genomic Medicine. Cleveland Clinic. Cleveland, Ohio, USA
Emily A. Mason
University of South Carolina School of Medicine. Columbia, South Carolina, USA
Andrea R.V.R. Horimoto
Division of Aging. Brigham and Women’s Hospital, Boston. Massachusetts, USA
Douglas P. Loesch
Institute for Genome Sciences. University of Maryland School of Medicine. Baltimore, Maryland, USA
Elif I. Sarihan
Lerner Research Institute. Genomic Medicine. Cleveland Clinic. Cleveland, Ohio, USA
Mario R. Cornejo-Olivas
Neurogenetics Working Group. Universidad Científica del Sur. Lima, Peru/Neurogenetics Research Center. Instituto Nacional de Ciencias Neurologicas. Lima, Peru
Luis E. Torres
Movement Disorders Unit. Instituto Nacional de Ciencias Neurologicas. Lima, Peru
Pilar E. Mazzetti-Soler
Neurogenetics Research Center. Instituto Nacional de Ciencias Neurologicas. Lima, Peru/Departamento de Medicina Humana. Universidad Nacional Mayor de San Marcos. Lima, Peru
Carlos Cosentino
Movement Disorders Unit. Instituto Nacional de Ciencias Neurologicas. Lima, Peru
Elison H. Sarapura-Castro
Neurogenetics Research Center. Instituto Nacional de Ciencias Neurologicas. Lima, Peru
Andrea Rivera-Valdivia
Neurogenetics Research Center. Instituto Nacional de Ciencias Neurologicas. Lima, Peru
Angel C. Medina
Universidad Nacional del Altiplano. Puno, Peru
Elena M. Dieguez
Neurology Institute. Universidad de la República. Montevideo, Uruguay
Víctor E. Raggio
Department of Genetics. Facultad de Medicina. Universidad de la República. Montevideo, Uruguay
Andrés Lescano
Neurology Institute. Universidad de la República. Montevideo, Uruguay
Vitor Tumas
Ribeirao Preto Medical School. Universidade de Sao Paulo. Ribeirao Preto, RS, Brazil
Vanderci Borges
Movement Disorders Unit. Department of Neurology and Neurosurgery. Universidade Federal de Sao Paulo. Sao Paulo, SP, Brazil
Henrique B. Ferraz
Movement Disorders Unit. Department of Neurology and Neurosurgery. Universidade Federal de Sao Paulo. Sao Paulo, SP, Brazil
Carlos R. Rieder
Departamento de Neurologia. Universidade Federal de Ciências da Saúde de Porto Alegre. Porto Alegre, RS, Brazil
Artur Schumacher Schuh
Serviço de Neurologia. Hospital de Clínicas de Porto Alegre. Porto Alegre, RS, Brazil/Departamento de Farm Fundaçao cologia. Universidade Federal do Rio Grande do Sul. Porto Alegre, RS, Brazil
Bruno L. Santos-Lobato
Instituto de Ciências da Saúde. Universidade Federal do Para. Belém, PA, Brazil
Carlos Velez-Pardo
Neuroscience Research Group. Medical Research Institute. Faculty of Medicine. Universidad de Antioquia. Medellín, Colombia
Marlene Jimenez-Del-Rio
Neuroscience Research Group. Medical Research Institute. Faculty of Medicine. Universidad de Antioquia. Medellín, Colombia
Francisco Lopera
Neuroscience Research Group. Medical Research Institute. Faculty of Medicine. Universidad de Antioquia. Medellín, Colombia
Sonia Moreno
Neuroscience Research Group. Medical Research Institute. Faculty of Medicine. Universidad de Antioquia. Medellín, Colombia
Pedro Chana-Cuevas
CETRAM. Facultad de Ciencias Médicas. Universidad de Santiago de Chile. Santiago, Chile
William Fernandez
Neuroscience and Cell Death Research Groups. Medical School and Genetic Institute. Universidad Nacional de Colombia. Bogota, Colombia
Gonzalo Arboleda
Neuroscience and Cell Death Research Groups. Medical School and Genetic Institute. Universidad Nacional de Colombia. Bogota, Colombia
Humberto Arboleda
Neuroscience and Cell Death Research Groups. Medical School and Genetic Institute. Universidad Nacional de Colombia. Bogota, Colombia
Carlos E. Arboleda Bustos
Neuroscience and Cell Death Research Groups. Medical School and Genetic Institute. Universidad Nacional de Colombia. Bogota, Colombia
Dora Yearout
Veterans Affairs Puget Sound Health Care System. Seattle, Washington, USA/Department of Neurology. University of Washington. Seattle, Washington, USA
Eduardo Tarazona-Santos
Department of Genetics. Ecology and Evolution. Institute of Biological Sciences. Universidade Federal de Minas Gerais. Belo Horizonte, MG, Brazil
Cyrus P. Zabetian
Veterans Affairs Puget Sound Health Care System. Seattle, Washington, USA/Department of Neurology. University of Washington. Seattle, Washington, USA
International Parkinson Disease Genomics Consortium (IPDGC),
Timothy A. Thornton
Department of Biostatistics. University of Washington. Seattle, Washington, USA
Timothy D. O’Connor
Institute for Genome Sciences. University of Maryland School of Medicine. Baltimore, Maryland, USA/Program in Health Equity and Population Health. University of Maryland School of Medicine. Baltimore, Maryland, USA/Program in Personalized and Genomic Medicine. University of Maryland School of Medicine. Baltimore, Maryland, USA/Department of Medicine. University of Maryland School of Medicine. Baltimore, Maryland, USA
Ignacio F. Mata
Lerner Research Institute. Genomic Medicine. Cleveland Clinic. Cleveland, Ohio, USA
Latin American Research Consortium on the Genetics of Parkinson’s Disease (LARGE-PD)
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