X-Chromosome Association Study in Latin American Cohorts Identifies New Loci in Parkinson Disease
Leal, T. P.; Rao, S. C.; French-Kwawu, J. N.; GOUVEIA, M. H.; Borda, V.; Inca-Martinez, M.; Mason, E. A.; Horimoto, A. R.; Loesch, D.; Sarihan, E. I.; Cornejo-Olivas, M. R.; Torres, L. E.; Mazzetti-Soler, P. E.; Cosentino, C.; Sarapura-Castro, E. H.; Rivera-Valdivia, A.; COLQUE, A. C. M.; Dieguez, E. M.; Raggio, V. E.; Lescano, A.; Tumas, V.; Borges, V.; Ferraz, H. B.; Rieder, C. R. M.; Schumacher-Schuh, A. F.; Santos-Lobato, B. L.; VELEZ-PARDO, C.; JIMENEZ-DEL-RIO, M.; Lopera, F. J.; Masmela, S. M.; Chana-Cuevas, P.; Fernandez, W.; Arboleda, G.; Arboleda, H.; Arboleda-Bustos, C. E.; Yearout,
Show 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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