<scp>X‐Chromosome</scp> Association Study in Latin American Cohorts Identifies New Loci in Parkinson's Disease
Thiago Peixoto Leal, Shilpa C. Rao, Jennifer N. French, Mateus H. Gouveia, Víctor Borda, Sara Bandrés‐Ciga, Miguel Inca‐Martinez, Emily Mason, Andréa R. V. R. Horimoto, Douglas P. Loesch, Elif Irem Sarihan, Mario Cornejo‐Olivas, Luis Torres, Pilar Mazzetti, Carlos Cosentino, Elison Sarapura‐Castro, Andrea Rivera‐Valdivia, Ángel C. Medina, Elena Diéguez, Víctor Raggio, Andrés G. Lescano, Vítor Tumas, Vanderci Borges, Henrique Ballalai Ferraz, Carlos Roberto de Mello Rieder, Artur Schumacher Schuh, Bruno Lopes Santos‐Lobato, Carlos Velez‐Pardo, Marlene Jiménez-Del-Río, Francisco Lopera, Sonia Moreno, Pedro Chaná‐Cuevas, William Fernández, Gonzálo Arboleda, Humberto Granados, Carlos Bustos, Dora Yearout, Maira Tonidandel Barbosa, Francisco Cardoso, Paulo Caramelli, Mauro César Quintão Cunningham, Débora Palma Maia, Maria Fernanda Lima‐Costa, Eduardo Tarazona‐Santos, Cyrus P. Zabetian, Timothy A. Thornton, Timothy D. O’Connor, Ignácio F. Mata
Abstract
BACKGROUND: Sex differences in Parkinson's disease (PD) risk are well-known. However, the role of sex chromosomes in the development and progression of PD is still unclear. OBJECTIVE: The objective of this study was to perform the first X-chromosome-wide association study for PD risk in a Latin American cohort. METHODS: We used data from three admixed cohorts: (1) Latin American Research consortium on the Genetics of Parkinson's Disease (n = 1504) as discover cohort, and (2) Latino cohort from International Parkinson Disease Genomics Consortium (n = 155) and (3) Bambui Aging cohort (n = 1442) as replication cohorts. We also developed an X-chromosome framework specifically designed for admixed populations. RESULTS: replication odds ratio: 0.60 [0.37-0.98], P = 0.04). rs5525496 is associated with multiple expression quantitative trait loci in brain and non-brain tissues, including RAB9B, H2BFM, TSMB15B, and GLRA4, but colocalization analysis suggests that rs5525496 may not mediate risk by expression of these genes. We also replicated a previous X-chromosome-wide association study finding (rs28602900), showing that this variant is associated with PD in non-European populations. CONCLUSIONS: Our results reinforce the importance of including X-chromosome and diverse populations in genetic studies. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.