Clinical and Genetic Analysis of Costa Rican Patients With Parkinson's Disease

Background: Most research in genomics of Parkinson's disease (PD) has been done in subjects of European ancestry, leading to sampling bias and leaving Latin American populations underrepresented. We sought to clinically characterize PD patients of Costa Rican origin and to sequence familial PD and atypical parkinsonism-associated genes in cases and controls.Methods: We enrolled 118 PD patients with 97 unrelated controls. Collected information included demographics, exposure to risk and protective factors, and motor and cognitive assessments. We sequenced coding and untranslated regions in familial PD and atypical parkinsonism-associated genes including GBA, SNCA, VPS35, LRRK2, GCH1, PRKN, PINK1, DJ-1, VPS13C, and ATP13A2.Results: Mean age of PD probands was 62.12 ± 13.51 years; 57.6% were male. The frequency of risk and protective factors averaged ~45%. Physical activity significantly correlated with better motor performance despite years of disease. Increased years of education were significantly associated with better cognitive function, whereas hallucinations, falls, mood disorders, and coffee consumption correlated with worse cognitive performance. We did not identify an association between tested genes and PD or any damaging homozygous or compound heterozygous variants. Rare variants in LRRK2 were nominally associated with PD; six were located between amino acids p.1620 and 1623 in the C-terminal-of-ROC (COR) domain of Lrrk2. Non-synonymous GBA variants (p.T369M, p.N370S, and p.L444P) were identified in three healthy individuals. One PD patient carried a pathogenic GCH1 variant, p.K224R.Discussion: This is the first study that describes sociodemographics, risk factors, clinical presentation, and genetics of Costa Rican patients with PD, adding information to genomics research in a Latino population.

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Clinical and genetic analysis of Costa Rican patients with Parkinson's disease.

10.1101/2020.09.29.20202432 ◽

2020 ◽

Author(s):

Gabriel Torrealba-Acosta ◽

Eric Yu ◽

Tanya Lobo-Prada ◽

Javier Ruiz-Martínez ◽

Ana Gorostidi-Pagola ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Protective Factors ◽

Latin American ◽

Rare Variants ◽

Coffee Consumption ◽

Risk And Protective Factors ◽

Costa Rican ◽

European Ancestry ◽

Compound Heterozygous

Abstract Background: Parkinson's disease (PD) involves environmental risk and protective factors as well as genetic variance. Most of the research in genomics has been done in subjects of European ancestry leading to sampling bias and leaving Latin American populations underrepresented. Objective: We sought to phenotype and genotype Costa Rican PD cases and controls. Methods: We enrolled 118 PD patients with 97 unrelated controls. Collected information included demographics, exposure to risk and protective factors, motor and cognitive assessments. We sequenced coding and untranslated regions in familial PD and atypical parkinsonism-associated genes including GBA, SNCA, VPS35, LRRK2, GCH1, PRKN, PINK1, DJ-1, VPS13C, ATP13A2. Results: Mean age of PD probands was 62.12 ± 13.51 years, 57.6% were male. Prevalence of risk and protective factors reached 30%. Physical activity significantly correlated with better motor performance despite years of disease. Increased years of education were significantly associated with better cognitive function, whereas hallucinations, falls, mood disorders and coffee consumption correlated with worse cognitive performance. We did not identify an association between tested genes and PD or any damaging homozygous or compound heterozygous variants. Rare variants in LRRK2 were nominally associated with PD, six were located between amino acids p.1620-1623 in the C-terminal-of-ROC (COR) domain of LRRK2. Nonsynonymous GBA variants (p.T369M, p.N370S, p.L444P) were identified in three healthy individuals. One PD patient carried a pathogenic GCH1 variant, p.K224R. Conclusion: This is the first study that reports on sociodemographic, risk factors, clinical presentation and genetics of Costa Rican patients with PD.

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Modifiable risk and protective factors in disease development, progression and clinical subtypes of Parkinson's disease: What do prospective studies suggest?

Neurobiology of Disease ◽

10.1016/j.nbd.2019.104671 ◽

2020 ◽

Vol 134 ◽

pp. 104671 ◽

Cited By ~ 5

Author(s):

Daniele Belvisi ◽

Roberta Pellicciari ◽

Giovanni Fabbrini ◽

Michele Tinazzi ◽

Alfredo Berardelli ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Protective Factors ◽

Prospective Studies ◽

Risk And Protective Factors ◽

Disease Development

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RIC3 variants are not associated with Parkinson's Disease in large European, Latin American, or East Asian cohorts

10.1101/2021.06.22.21259012 ◽

2021 ◽

Author(s):

Kajsa Brolin ◽

Sara Bandres Ciga ◽

Hampton Leonard ◽

Mary B Makarious ◽

Cornelis Blauwendraat ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Latin American ◽

Rare Variants ◽

Neurodegenerative Disorder ◽

Disease Risk ◽

East Asian ◽

European Ancestry ◽

Common Genetic Variants

Parkinson's disease (PD) is a complex neurodegenerative disorder in which both rare and common genetic variants contribute to disease risk. Multiple genes have been reported to be linked to monogenic PD, but these only explain a fraction of the observed familial aggregation. Rare variants in RIC3 have been suggested to be associated with PD in the Indian population. However, replication studies yielded inconsistent results. We further investigate the role of RIC3 variants in PD in European cohorts using individual-level genotyping data from 14,671 PD patients and 17,667 controls, as well as whole-genome sequencing data from 1,615 patients and 961 controls. We also investigated RIC3 using summary statistics from a Latin American cohort of 1,481 individuals, and from a cohort of 31,575 individuals of East Asian ancestry. We did not identify any association between RIC3 and PD in any of the cohorts. However, more studies of rare variants in non-European ancestry populations, in particular South Asian populations, are necessary to further evaluate the world-wide role of RIC3 in PD etiology.

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Respiratory dysfunction in Parkinson's disease: a narrative review

ERJ Open Research ◽

10.1183/23120541.00165-2020 ◽

2020 ◽

Vol 6 (4) ◽

pp. 00165-2020

Author(s):

Andrea D'Arrigo ◽

Stefano Floro ◽

Francesca Bartesaghi ◽

Chiara Casellato ◽

Giuseppe Francesco Sferrazza Papa ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Protective Factors ◽

Respiratory Symptoms ◽

Current Knowledge ◽

Atypical Parkinsonism ◽

Ventilatory Control ◽

Respiratory Dysfunction ◽

Pathogenetic Mechanisms ◽

The Impact

The presence of respiratory symptoms in Parkinson's disease (PD) has been known since the first description of the disease, even though the prevalence and incidence of these disturbances are not well defined. Several causes have been reported, comprising obstructive and restrictive pulmonary disease and changes in the central ventilatory control, and different pathogenetic mechanisms have been postulated accordingly. In our review, we encompass the current knowledge about respiratory abnormalities in PD, as well as the impact of anti-Parkinsonian drugs as either risk or protective factors. A description of putative pathogenetic mechanisms is also provided, and possible treatments are discussed, focusing on the importance of recognising and treating respiratory symptoms as a key manifestation of the disease itself. A brief description of respiratory dysfunctions in atypical Parkinsonism, especially α-synucleinopathies, is also provided.

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Risk and protective factors for Parkinson's disease: A study in Swedish twins

Annals of Neurology ◽

10.1002/ana.20307 ◽

2004 ◽

Vol 57 (1) ◽

pp. 27-33 ◽

Cited By ~ 82

Author(s):

Karin Wirdefeldt ◽

Margaret Gatz ◽

Yudi Pawitan ◽

Nancy L. Pedersen

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Protective Factors ◽

Risk And Protective Factors

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Causal Association between Periodontitis and Parkinson’s Disease: A Bidirectional Mendelian Randomization Study

Genes ◽

10.3390/genes12050772 ◽

2021 ◽

Vol 12 (5) ◽

pp. 772

Author(s):

João Botelho ◽

Vanessa Machado ◽

José João Mendes ◽

Paulo Mascarenhas

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Instrumental Variables ◽

Mendelian Randomization ◽

Association Studies ◽

European Ancestry ◽

Genome Wide Association Studies ◽

Nucleotide Polymorphisms ◽

Genetic Liability ◽

Bidirectional Association

The latest evidence revealed a possible association between periodontitis and Parkinson’s disease (PD). We explored the causal relationship of this bidirectional association through two-sample Mendelian randomization (MR) in European ancestry populations. To this end, we used openly accessible data of genome-wide association studies (GWAS) on periodontitis and PD. As instrumental variables for periodontitis, seventeen single-nucleotide polymorphisms (SNPs) from a GWAS of periodontitis (1817 periodontitis cases vs. 2215 controls) and eight non-overlapping SNPs of periodontitis from an additional GWAS for validation purposes. Instrumental variables to explore for the reverse causation included forty-five SNPs from a GWAS of PD (20,184 cases and 397,324 controls). Multiple approaches of MR were carried-out. There was no evidence of genetic liability of periodontitis being associated with a higher risk of PD (B = −0.0003, Standard Error [SE] 0.0003, p = 0.26). The eight independent SNPs (B = −0.0000, SE 0.0001, p = 0.99) validated this outcome. We also found no association of genetically primed PD towards periodontitis (B = −0.0001, SE 0.0001, p = 0.19). These MR study findings do not support a bidirectional causal genetic liability between periodontitis and PD. Further GWAS studies are needed to confirm the consistency of these results.

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Cross-Cultural Validation of the Scales for Outcomes in Parkinson's Disease-Psychosocial Questionnaire (SCOPA-PS) in Four Latin American Countries

Value in Health ◽

10.1111/j.1524-4733.2008.00436.x ◽

2009 ◽

Vol 12 (2) ◽

pp. 385-391 ◽

Cited By ~ 9

Author(s):

Javier Virués-Ortega ◽

Francisco Javier Carod-Artal ◽

Marcos Serrano-Dueñas ◽

Gabriela Ruiz-Galeano ◽

Gloria Meza-Rojas ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Latin American ◽

Cross Cultural ◽

Latin American Countries ◽

Cultural Validation

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Differences in MTHFR and LRRK2 variant’s association with sporadic Parkinson’s disease in Mexican Mestizos correlated to Native American ancestry

npj Parkinson s Disease ◽

10.1038/s41531-021-00157-y ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Elizabeth Romero-Gutiérrez ◽

Paola Vázquez-Cárdenas ◽

Hortensia Moreno-Macías ◽

José Salas-Pacheco ◽

Teresa Tusié-Luna ◽

...

Keyword(s):

Risk Factors ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Native American ◽

Neurodegenerative Disorder ◽

European Ancestry ◽

Native American Ancestry ◽

Risk Effect ◽

Mexican Mestizos ◽

Shared Risk

AbstractParkinson’s disease (PD), a common neurodegenerative disorder, has a complex etiology where environmental and genetic factors intervene. While a number of genes and variants have been identified in recent decades as causative or protective agents of this condition, a limited number of studies have been conducted in mixed populations, such as Mexican Mestizos. The historical convergence of two founding groups and three ethnicities, and the increasing north-to-south gradient of Native American ancestry in Mexico resulted in a subpopulation structure with considerable genetic diversity. In this work, we investigate the influence of 21 known susceptibility variants for PD. Our case–control study, with a cohort of 311 Mexican Mestizo subjects, found a significant risk association for the variant rs1491942 in LRRK2. However, when stratification by ancestry was performed, a risk effect for MTHFR rs1801133 was observed only in the group with the highest percentage of European ancestry, and the PD risk effect for LRRK2 rs1491942 was significant in subjects with a higher ratio of Native American ancestry. Meta-analyses of these SNP revealed the effect of LRRK2 rs1491942 to be even more significant than previously described in populations of European descent. Although corroboration is necessary, our findings suggest that polymorphism rs1491942 may be useful as a risk marker of PD in Mexican Mestizos with greater Native American ancestry. The absence of associations with the remaining known risk factors is, in itself, a relevant finding and invites further research into the shared risk factors’ role in the pathophysiological mechanisms of this neurodegenerative disorder.

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