X-Chromosome Association Study in Latin American Cohorts Identifies New Loci in Parkinson Disease

Thiago Peixoto Leal; Jennifer N. French; Mateus Henrique Gouveia; Víctor Borda; Miguel Inca‐Martinez; Emily A Mason; Andréa R. V. R. Horimoto; Douglas P. Loesch; Elif Irem Sarihan; Mario Cornejo‐Olivas; Luis Torres; Pilar Mazzetti; Carlos Cosentino; Elison H. Sarapura‐Castro; Andrea Rivera‐Valdivia; Ángel C. Medina; Elena Diéguez; Víctor E. Raggio; Andrés Lescano; Vítor Tumas; Vanderci Borges; Henrique Ballalai Ferraz; Carlos Roberto de Mello Rieder; Artur Francisco Schumacher Schuh; Bruno Lopes Santos‐Lobato; Carlos Velez‐Pardo; Marlene Jiménez-Del-Río; Francisco Javier Lopera; Sonia Moreno; Pedro Chaná‐Cuevas

doi:10.1101/2023.01.31.23285199

Genetic & Genomic MedicinemedRxivJan 31, 2023

Preprint

X-Chromosome Association Study in Latin American Cohorts Identifies New Loci in Parkinson Disease

Thiago Peixoto Leal iD, Jennifer N. French iD, Mateus Henrique Gouveia iD, Víctor Borda iD, Miguel Inca‐Martinez iD, Emily A Mason iD, Andréa R. V. R. Horimoto iD, Douglas P. Loesch iD, Elif Irem Sarihan iD, Mario Cornejo‐Olivas iD, Luis Torres iD, Pilar Mazzetti iD, Carlos Cosentino iD, Elison H. Sarapura‐Castro iD, Andrea Rivera‐Valdivia iD, Ángel C. Medina, Elena Diéguez, Víctor E. Raggio iD, Andrés Lescano, Vítor Tumas iD, Vanderci Borges iD, Henrique Ballalai Ferraz iD, Carlos Roberto de Mello Rieder iD, Artur Francisco Schumacher Schuh iD, Bruno Lopes Santos‐Lobato iD, , Ignacio Fernandez Mata iD

Abstract

Sex differences in Parkinson Disease (PD) risk are well-known. However, it is still unclear the role of sex chromosomes in the development and progression of PD. We performed the first X-chromosome Wide Association Study (XWAS) for PD risk in Latin American individuals. We used data from three admixed cohorts: (i) Latin American Research consortium on the GEnetics of Parkinsons Disease (n=1,504) as discover cohort and (ii) Latino cohort from International Parkinson Disease Genomics Consortium (n = 155) and (iii) Bambui Aging cohort (n= 1,442) as replication cohorts. After developing a X-chromosome framework specifically designed for admixed populations, we identified eight linkage disequilibrium regions associated with PD. We fully replicated one of these regions (top variant rs525496; discovery OR [95%CI]: 0.60 [0.478 - 0.77], p = 3.13 x 10-5 ; replication OR: 0.60 [0.37-0.98], p = 0.04). rs525496 is an expression quantitative trait loci for several genes expressed in brain tissues, including RAB9B, H2BFM, TSMB15B and GLRA4. We also replicated a previous XWAS finding (rs28602900), showing that this variant is associated with PD in non-European populations. Our results reinforce the importance of including X-chromosome and diverse populations in genetic studies.

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