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Genome-wide Analysis of Copy Number Variation in Latin American Parkinson's Disease Patients.

Sarihan, E.I., Pérez‐Palma, E., Niestroj, L.‐M., Loesch, D., Inca‐Martinez, M., Horimoto, A.R., Cornejo‐Olivas, M., Torres, L., Mazzetti, P., Cosentino, C., Sarapura‐Castro, E., Rivera‐Valdivia, A., Dieguez, E., Raggio, V., Lescano, A., Tumas, V., Borges, V., Ferraz, H.B., Rieder, C.R., Schumacher‐Schuh, A.F., Santos‐Lobato, B.L., Velez‐Pardo, C., Jimenez‐Del‐Rio, M., Lopera, F., Moreno, S., Chana‐Cuevas, P., Fernandez, W., Arboleda, G., Arboleda, H., Arboleda‐Bustos, C.E., Yearout, D., Zabetian, C.P., Thornton, T.A., O'Connor, T.D., Lal, D., Mata, I.F. and (2021), Genome‐Wide Analysis of Copy Number Variation in Latin American Parkinson's Disease Patients. Mov Disord, 36: 434-441. https://doi.org/10.1002/mds.28353

The overall identification of copy number variants (CNV) at a genome-wide level has been understudied in PD patients since most studies only screen a few known PD genes. Here we used genome-wide genotyping data from 747 PD patients and 632 ancestry matched controls from LARGE-PD to understand the genome-wide burden of copy number variants in Latinos and its association with disease:

  • Genome-wide copy number burden analysis showed no difference between patients vs. controls.
  • Patients were significantly enriched for CNVs overlapping known PD genes (OR: 3.97 [1.69 - 10.5], P = 0.018), with PARK2 showing the strongest burden.
  • Patients carrying a CNV in known PD genes present an disease symptoms 26 years earlier compared to patients with CNVs in other genes.
  • In Latin America 5.6% of Early-Onset PD patients carry a CNV in PARK2.
    • The distribution and risk effect of GBA_ first page 2pic

    The distribution and risk effect of GBA variants in a large cohort of PD patients from Colombia and Peru.

    Velez-Pardo C, Lorenzo-Betancor O, Jimenez-Del-Rio M, Moreno S, Lopera F, Cornejo-Olivas M, Torres L, Inca-Martinez M, Mazzetti P, Cosentino C, Yearout D, Waldherr SM, Zabetian CP, Mata IF. Parkinsonism Relat Disord.2019 Jun;63:204-208. doi: 10.1016/j.parkreldis.2019.01.030.Epub 2019 Feb 4.

    GBA is the most important risk factor for PD, however little is known about its effects on Latinos. Here we screened 602 PD patients and 319 controls from Colombia and Peru. The key findings were:

  • GBA is an important risk factor in these populations too, increase the risk to develop PD around 4.5 and 6.2 fold in Peru and Colombia respectively.
  • While frequency in PD patients from Peru is similar to the frequency in other countries (5.5%), frequency in Colombia is double (9.9%) due to the presence of a newly described population-specific mutation (p.K198E).
  • Mutations in GBA not only increase the risk to develop PD but also advances the age at onset by about 8 years.
    • LARGE-PD_Examinig the Genetics of PD in Latam_first page pic

    LARGE-PD: Examining the Genetics of Parkinson’s Disease in Latin America.

    Zabetial CP, Mata IF on behalf of the Latin American Research Consortium on the Genetics of PD (LARGE-PD) Mov Disord . 2017 Sep;32(9):1330-1331. doi: 10.1002/mds.27081. Epub 2017 Jun 28.

    Mutations located in codons G2019 and R1441 of the leucine-rich repeat kinase 2 (LRRK2) gene represent the most common genetic cause of PD in patients of European origin. Here, we show that, in the LARGE-PD cohort, the combined frequency of these LRRK2 mutations varies substantially across countries in Latin America and is directly correlated with the estimated proportion of European ancestry at each site. This indicates that the genetic architecture of PD might differ between Latinos and other population groups, as it has been shown in several other diseases, including cancer

    See a complete list of publications for Ignacio Mata, PhD on PubMed.