Most recent publication
X chromosome-wide association studies in neurological disorders: uncovering the hidden influence of the X chromosome
Step K, Leal TP, Kamel WA, Waldo E, Bardien S, Mata IF. X chromosome-wide association studies in neurological disorders: uncovering the hidden influence of the X chromosome. Front Genet. 2025 Jul 30;16:1650259. doi: 10.3389/fgene.2025.1650259. PMID: 40809846; PMCID: PMC12343220.
Abstract
X chromosome-wide association studies (XWAS) have identified susceptibility variants for various neurodegenerative and neurodevelopmental diseases. The unique characteristics of the chromosome require more complex analytical approaches than standard genome-wide association studies. Over the past 2 decades, refined XWAS methods have better accounted for this biology. Given that many neurological diseases show sex-biased prevalence, XWAS offers a valuable framework for investigating sex-specific genetic contributions. This review summarizes published neurological XWAS (N = 10), highlighting methodological approaches. Despite the challenges of genetic analyses for the X chromosome, XWAS remains a key approach for studying its role in disease mechanisms.
Additional Publications
LRRK2: Genetic mechanisms vs genetic subtypes
Thomas Hugentobler Schlickmann, Marcelo Somma Tessari, Wyllians Vendramini Borelli, Gabriel Alves Marconi, Gabriela Magalhães Pereira Eduardo Zimmer, Alastair Noyce, Ignacio Fernandez Mata, Carlos Roberto de Mello Rieder, Daniel Teixeira-dos-Santos, Artur Francisco Schumacher Schuh. “Prevalence, Distribution and Future Projections of Parkinson Disease in Brazil: Insights from the ELSI-Brazil Cohort Study.” The Lancet Regional Health - Americas, vol. 44, 30 Mar. 2025, pp. 101046–101046, www.thelancet.com/journals/lanam/article/PIIS2667-193X(25)00056-0/fulltext, https://doi.org/10.1016/j.lana.2025.101046.
Sex differences in the diagnosis latency of Parkinson's disease in Latin America
Ramchandra J, Inca-Martinez M, Leal TP, Chaparro-Solano HM, Salim A, Gatto EM, Rojas NG, Da Prat G, Micheli F, Santos-Lobato BL, Cardoso FEC, Camargos S, Letro GH, Braga-Neto P, Peixoto VMT, Schuh AFS, Tumas V, Brito MM, Borges V, Candeias da Silva C, Ferraz HB, Chana-Cuevas P, Saffie-Awad P, Olguin P, Colombo A, de la Cerda A, Farías GA, Nuñez JC, Arboleda G, Arboleda H, Fernandez W, Arboleda-Bustos CE, Orozco JL, Muñoz-Ospina B, Velez-Pardo C, Jiménez-Del-Río M, Lopera F, Moreno S, Pineda DA, Buritica O, Torrealba-Acosta G, Medina Escobar A, Rodríguez-Violante M, Hernández-Medrano AJ, Martinez-Ramirez D, González-González M, Rentería ME, Alcauter S, Reyes-Pérez P, Medina-Rivera A, Vazquez-Guevara D, de María Ugalde-Mejía L, Valadez M MJ, Cárdenas-Sáenz O, Rodríguez-Leyva I, Guerra-Galicia CM, Gandarilla-Martínez NA, Matuk-Pérez Y, Morelos-Figaredo E, Salinas-Barboza K, Isais-Millán S, Pérez-Torres T, Deras Gaucin DC, Ruiz-Contreras AE, Estrada-Bellmann I, Rios-Pinto J, Cornejo-Olivas M, Cosentino C, Torres Ramirez L, Mori N, Mejía-Rojas K, Medina ÁC, Cornejo-Herrera I, Ochoa EM, Viñuela Á, Dieguez E, Amorín I, Lescano A, Mata IF. Sex differences in the diagnosis latency of Parkinson's disease in Latin America. Parkinsonism Relat Disord. 2025 May;134:107344. doi: 10.1016/j.parkreldis.2025.107344. Epub 2025 Feb 25. PMID: 40058072.
Multi-ancestry genome-wide association meta-analysis of Parkinson’s disease
Jonggeol Jeffrey Kim, Dan Vitale, Diego Véliz Otani, Michelle Mulan Lian, Karl Heilbron, the 23andMe Research Team, Hirotaka Iwaki, Julie Lake, Caroline Warly Solsberg, Hampton Leonard, Mary B. Makarious, Eng-King Tan, Andrew B. Singleton, Sara Bandres-Ciga, Alastair J. Noyce, the Global Parkinson’s Genetics Program (GP2), Cornelis Blauwendraat, Mike A. Nalls, Jia Nee Foo & Ignacio Mata “Multi-Ancestry Genome-Wide Association Meta-Analysis of Parkinson’s Disease.” Nature Genetics, vol. 56, no. 1, 28 Dec. 2023, pp. 27–36, www.nature.com/articles/s41588-023-01584-8#Sec2, https://doi.org/10.1038/s41588-023-01584-8.
X-Chromosome Association Study in Latin American Cohorts Identifies New Loci in Parkinson's Disease
Leal TP, Rao SC, French-Kwawu JN, Gouveia MH, Borda V, Bandres-Ciga S, Inca-Martinez M, Mason EA, Horimoto ARVR, Loesch DP, Sarihan EI, Cornejo-Olivas MR, Torres LE, Mazzetti-Soler PE, Cosentino C, Sarapura-Castro EH, Rivera-Valdivia A, Medina AC, Dieguez EM, Raggio VE, Lescano A, Tumas V, Borges V, Ferraz HB, Rieder CR, Schumacher Schuh A, Santos-Lobato BL, Velez-Pardo C, Jimenez-Del-Rio M, Lopera F, Moreno S, Chana-Cuevas P, Fernandez W, Arboleda G, Arboleda H, Arboleda Bustos CE, Yearout D, Barbosa MT, Cardoso FEC, Caramelli P, Cunningham MCQ, Maia DP, Lima-Costa MF, Tarazona-Santos E, Zabetian CP; International Parkinson Disease Genomics Consortium (IPDGC); Thornton TA, O'Connor TD, Mata IF; Latin American Research Consortium on the Genetics of Parkinson's Disease (LARGE-PD). X-Chromosome Association Study in Latin American Cohorts Identifies New Loci in Parkinson's Disease. Mov Disord. 2023 Sep;38(9):1625-1635. doi: 10.1002/mds.29508. Epub 2023 Jul 20. PMID: 37469269; PMCID: PMC10524402.
Association of women-specific health factors in the severity of Parkinson’s disease
Shilpa C. Rao, Yadi Li, Brittany Lapin, Sreya Pattipati, Kamalini Ghosh Galvelis, Anna Naito, Nicolas Gutierrez, Thiago Peixoto Leal, Amira Salim, Philippe A. Salles, Maria De Leon & Ignacio F. Mata “Association of Women-Specific Health Factors in the Severity of Parkinson’s Disease.” Npj Parkinson’s Disease, vol. 9, no. 1, 5 June 2023, pp. 1–16, www.nature.com/articles/s41531-023-00524-x, https://doi.org/10.1038/s41531-023-00524-x.
Polygenic risk prediction and SNCA haplotype analysis in a Latino Parkinson's disease cohort
Douglas P. Loesch, Andrea R.V.R. Horimoto, Elif Irem Sarihan, Miguel Inca-Martinez, Emily Mason, Mario Cornejo-Olivas, Luis Torres, Pilar Mazzetti, Carlos Cosentino, Elison Sarapura-Castro, Andrea Rivera-Valdivia, Angel C. Medina, Elena Dieguez, Victor Raggio, Andres Lescano, Vitor Tumas, Vanderci Borges, Henrique B. Ferraz, Carlos R. Rieder, Artur Schumacher-Schuh, Timothy D. O'Connor “Polygenic Risk Prediction and SNCA Haplotype Analysis in a Latino Parkinson’s Disease Cohort.” Parkinsonism & Related Disorders, vol. 102, 1 Sept. 2022, pp. 7–15, www.sciencedirect.com/science/article/pii/S1353802022001936, https://doi.org/10.1016/j.parkreldis.2022.06.010.
Promoting Gender Inclusivity: A Questionnaire for Women's Health Factors in Parkinson's Disease
Shilpa C. Rao BS, Sreya Pattipati, Amira Salim BS, Nicolas Gutierrez BS, Anna Naito PhD, Kamalini Ghosh MS, Maria De Leon MD, Ignacio Mata PhD “Promoting Gender Inclusivity: A Questionnaire for Women’s Health Factors in Parkinson’s Disease.” Movement Disorders, vol. 37, no. 5, May 2022, pp. 1112–1113, https://doi.org/10.1002/mds.29020.
Genome-Wide Analysis of Copy Number Variation in Latin American Parkinson's Disease Patients
Elif Irem Sarihan MD, Eduardo Pérez-Palma PhD, Lisa-Marie Niestroj PhD, Douglas Loesch BA, AS, Miguel Inca-Martinez BS, Andrea R.V.R. Horimoto PhD, Mario Cornejo-Olivas MD, Luis Torres MD, Pilar Mazzetti MD, Carlos Cosentino MD, Elison Sarapura-Castro MD, Andrea Rivera-Valdivia MD, Elena Dieguez MD, Victor Raggio MD, Andres Lescano MD, Vitor Tumas MD, PhD, Vanderci Borges MD, PhD, Henrique B. Ferraz MD, PhD, Carlos R. Rieder PhD, Artur F. Schumacher-Schuh MD, PhD, Bruno L. Santos-Lobato MD, PhD, Carlos Velez-Pardo PhD, Marlene Jimenez-Del-Rio PhD, Francisco Lopera MD, Sonia Moreno PhD, Pedro Chana-Cuevas MD, William Fernandez MD, Gonzalo Arboleda MD, PhD, Humberto Arboleda MD, MS, Carlos E. Arboleda-Bustos PhD, Dora Yearout BS, Cyrus P. Zabetian MD, MS, Timothy A. Thornton PhD, Timothy D. O'Connor PhD, Dennis Lal PhD, Ignacio F. Mata PhD, and members of theLatin American Research Consortium on the Genetics of Parkinson's Disease (LARGE-PD)‡ “Genome‐Wide Analysis of Copy Number Variation in Latin American Parkinson’s Disease Patients.” Movement Disorders, vol. 36, no. 2, 5 Nov. 2020, pp. 434–441, https://doi.org/10.1002/mds.28353.
The distribution and risk effect of GBA variants in a large cohort of PD patients from Colombia and Peru
Carlos Velez-Pardo, Oswaldo Lorenzo-Betancor, Marlene Jimenez-Del-Rio, Sonia Moreno, Francisco Lopera, Mario Cornejo-Olivas, Luis Torres, Miguel Inca-Martinez, Pilar Mazzetti, Carlos Cosentino, Dora Yearout, Sarah M. Waldherr, Cyrus P. Zabetian, Ignacio F. Mata “The Distribution and Risk Effect of GBA Variants in a Large Cohort of PD Patients from Colombia and Peru.” Parkinsonism & Related Disorders, vol. 63, 4 Feb. 2019, pp. 204–208, www.prd-journal.com/article/S1353-8020(19)30030-6/fulltext, https://doi.org/10.1016/j.parkreldis.2019.01.030.
Variable frequency of LRRK2 variants in the Latin American research consortium on the genetics of Parkinson’s disease (LARGE-PD), a case of ancestry
Mario Cornejo-Olivas, Luis Torres, Mario R. Velit-Salazar, Miguel Inca-Martinez, Pilar Mazzetti, Carlos Cosentino, Federico Micheli, Claudia Perandones, Elena Dieguez, Victor Raggio, Vitor Tumas, Vanderci Borges, Henrique B. Ferraz, Carlos R. M. Rieder, Artur Shumacher-Schuh, Carlos Velez-Pardo, Marlene Jimenez-Del-Rio, Francisco Lopera, Jorge Chang-Castello, Brennie Andreé-Munoz, Sarah Waldherr, Dora Yearout, Cyrus P. Zabetian & Ignacio F. Mata “Variable Frequency of LRRK2 Variants in the Latin American Research Consortium on the Genetics of Parkinson’s Disease (LARGE-PD), a Case of Ancestry.” Npj Parkinson’s Disease, vol. 3, no. 1, 2 June 2017, www.nature.com/articles/s41531-017-0020-6#citeas, https://doi.org/10.1038/s41531-017-0020-6.
LARGE-PD: Examining the genetics of Parkinson's disease in Latin America
Zabetian, Cyrus P, and Ignacio F. Mata. “LARGE-PD: Examining the Genetics of Parkinson’s Disease in Latin America.” Movement Disorders, vol. 32, no. 9, 28 June 2017, pp. 1330–1331, https://doi.org/10.1002/mds.27081.
LRRK2 mutations in patients with Parkinson's disease from Peru and Uruguay
Ignacio F. Mata, Carlos Cosentino, Victoria Marca, Luis Torres, Pilar Mazzetti, Olimpio Ortega, Victor Raggio, Ruth Aljanati, Ricardo Buzó, Dora Yearout, Elena Dieguez, Cyrus P. Zabetian "LRRK2 mutations in patients with Parkinson's disease from Peru and Uruguay" Parkinsonism & Related Disorders, Volume 15, Issue 5, 2009, Pages 370-373, ISSN 1353-8020, https://doi.org/10.1016/j.parkreldis.2008.09.002 (https://www.sciencedirect.com/science/article/pii/S1353802008002538)
LRRK2 mutations are a common cause of Parkinson's disease in Spain
Mata IF, Ross OA, Kachergus J, Huerta C, Ribacoba R, Moris G, Blazquez M, Guisasola LM, Salvador C, Martinez C, Farrer M, Alvarez V. LRRK2 mutations are a common cause of Parkinson's disease in Spain. Eur J Neurol. 2006 Apr;13(4):391-4. doi: 10.1111/j.1468-1331.2006.01256.x. PMID: 16643318.
LRRK2 R1441G in Spanish patients with Parkinson's disease
Ignacio F. Mata, Julie P. Taylor, Jennifer Kachergus, Mary Hulihan, Cecilia Huerta, Carlos Lahoz, Marta Blazquez, Luis M. Guisasola, Carlos Salvador, Renee Ribacoba, Carmen Martinez, Matthew Farrer, Victoria Alvarez, LRRK2 R1441G in Spanish patients with Parkinson's disease, Neuroscience Letters, Volume 382, Issue 3, 2005, Pages 309-311, ISSN 0304-3940, https://doi.org/10.1016/j.neulet.2005.03.033. (https://www.sciencedirect.com/science/article/pii/S0304394005003289)