Miguel Inca-Martinez

The genetics of Parkinson’s disease (PD) in underrepresented populations remain poorly characterized, potentially overlooking population-specific contributions. We analyzed 461 Chilean PD cases from a movement disorders center. Pathogenic, likely pathogenic, or GBA1 risk variants were identified in 58 individuals (12.6%), mainly in LRRK2 (50%) and GBA1 (44.8%), while PRKN, SNCA , and SQSTM1 collectively represented 5.2%. All LRRK2 variants were p.G2019S, with an overall frequency of 6.3%, the highest reported in South America, and enrichment of Ashkenazi Jewish ancestry at this locus. These findings characterize the genetic landscape of PD in Chile and support its relevance for LRRK2 -targeted studies.

Background: Evidence on environmental determinants of Parkinson’s disease (PD) in Latin America is limited and their attributable burden remains poorly defined in the region. We examined associations between environmental exposures and PD and quantified their contribution to disease burden.Methods: We analyzed 9887 participants from nine Latin American countries in a case control study. Associations between environmental exposures and PD were estimated using logistic regression adjusted for age, sex, and country. Population attributable fractions (PAFs) were calculated for positively associated exposures, defined as severe head trauma or at least 5 years of exposure for other risk factors.Findings: Weekly caffeine consumption and tobacco use for at least 5 years were inversely associated with PD (adjusted OR [aOR] 0·77, p < 0·0001; aOR 0·83, p = 0·0009). Severe head trauma (aOR 1·35, p < 0·0001), occupational pesticide exposure (aOR 1·42, p = 0·0003), occupational metal exposure (aOR 1·29, p = 0·0299), rural living (aOR 1·60, p < 0·0001), and well water consumption (aOR 1·22, p = 0·0014) were positively associated with PD. Dose related associations were observed for caffeine, tobacco, occupational pesticides and metals, rural living, and well water consumption. The joint PAF across five risk exposures was 13·7% (95% CI 9·8 to 17·3), with higher estimates in El Salvador, Brazil, Colombia, males, and participants younger than 60 years. Sensitivity and lag analyses were directionally consistent.Interpretation: Selected environmental exposures may account for a meaningful proportion of PD burden in Latin America, supporting further research and public health attention to environmental determinants in the region.

Background: Although levodopa is the gold standard treatment for Parkinson's disease (PD), its chronic use is associated with levodopa-induced dyskinesia (LID), a motor complication that impacts prognosis, quality of life, and treatment costs. Most known LID-associated factors have been identified in European-descendant populations. Objectives: To describe the epidemiology of LID in Latin American and Caribbean (LATAM) countries and assess the relevance of known and novel LID-associated factors in this population. Methods: We conducted a cross-sectional study using data from the Latin American Research consortium on the Genetics of Parkinson's Disease (LARGE-PD). We included PD patients with information on LID status and levodopa use from eight LATAM countries. LID prevalence was calculated overall and by country. Countries were compared on demographic and clinical variables. Logistic regression was used to identify associations with LID. Results: A total of 3695 PD patients (58.8% male) were included. Overall LID prevalence was 25.4% [95% CI: 24.06–26.87], ranging from 9.3% in Colombia to 45.1% in Puerto Rico. Prevalence increased progressively with longer disease duration. Country comparisons showed that not all known LID-associated factors explained prevalence differences. In logistic regression, fast disease progression was significantly associated with LID (OR: 1.55, 95%CI: 1.16–2.07), while sex was not (OR: 1.02, 95%CI: 0.87–1.18). Conclusions: This is the largest study on LID epidemiology in LATAM. While some known risk factors remain relevant, others, like sex, do not, underscoring the need for population-specific studies. Future work should integrate environmental, clinical, and genetic data to better understand LID mechanisms.

Background: The global prevalence of Parkinson's disease (PD) is estimated to be 315 per 100,000 inhabitants, with variations across regions and depending on the epidemiological methods used. Door‐to‐door prevalence studies in Andean communities are notably underrepresented in the literature. Objective: The aim of this study was to estimate the PD prevalence in Jauja. Methods: A cross‐sectional community‐based door‐to‐door prevalence study was conducted from April 2018 to September 2019. We used a Spanish version of the 9‐item screening questionnaire (9‐item SQ). Trained interviewers conducted face‐to‐face screening surveys. Participants presenting “suspected parkinsonism” underwent further neurological assessment. PD cases responded to the LARGE‐PD questionnaire and “pesticide exposure questionnaire.” We calculated the crude prevalence, gender‐ and age‐specific rates, and age‐adjusted rates. Results: Out of 2527 eligible individuals, 1960 completed the screening survey. Of these, 563 were selected for neurological assessment, and 337 underwent neurological examination. PD was confirmed in 21 individuals, 16 of whom were identified using the 9‐item SQ with a crude prevalence of 816/100,000. We observed higher rates of PD in older age groups and in males compared to females (1.6 vs. 0.3%, P < 0.05). The age‐standardized prevalence was 566/100,000 (95% confidence interval [CI]: 496.6–635.2). Among PD cases, the most common environmental exposures were living near farming fields and pesticide exposure. Conclusions: The observed prevalence of PD in this town in the central highlands of Peru aligns with previous reports, with notably higher rates among individuals over the age of 80. Further prospective studies are warranted to investigate the potential influence of environmental factors on PD prevalence in this region.

Background: Although levodopa remains the gold standard treatment for Parkinson’s disease (PD), its chronic use is associated with levodopa-induced dyskinesia (LID), a motor complication that impacts prognosis, quality of life, and treatment costs. Most known LID-associated factors have been identified in European-descendant populations. Objectives: To describe the epidemiology of LID in Latin American and Caribbean (LATAM) countries and assess the relevance of known and novel LID-associated factors in this population. Methods: We conducted a cross-sectional study using data from the Latin American Research consortium on the Genetics of Parkinson’s Disease (LARGE-PD). We included PD patients with information on LID status and levodopa use from eight LATAM countries. LID prevalence was calculated overall and by country. Countries were compared on demographic and clinical variables. Logistic regression was used to identify associations with LID. Results: A total of 3,695 PD patients (58.8% male) were included. Overall LID prevalence was 25.4% [95% CI: 24.06–26.87], ranging from 9.3% in Colombia to 45.1% in Puerto Rico. Prevalence increased progressively with longer disease duration. Country comparisons showed that not all known LID-associated factors explained prevalence differences. In logistic regression, fast disease progression was significantly associated with LID (OR: 1.55, 95%CI: 1.16–2.07), while sex was not (OR: 1.02, 95%CI: 0.87–1.18). Conclusions: This is the largest study on LID epidemiology in LATAM. While some known risk factors remain relevant, others, like sex, do not, underscoring the need for population-specific studies. Future work should integrate environmental, clinical, and genetic data to better understand LID mechanisms.

Objective: This study aims to describe the establishment of the Mexican Parkinson’s Research Network (MEX-PD), a consortium dedicated to investigating the clinical, genetic, environmental, and neurophysiological underpinnings of phenotypic diversity in Mexican Parkinson’s disease (PD) patients and to present preliminary clinical and genetic outcomes. Methods: PD patients and control participants were recruited from medical centers across Mexico. The initial recruitment phase involved comprehensive neurological evaluations, cognitive assessments, and DNA collection. We conducted classical statistical analyses on clinical variables. Secondly, following genotyping with NeuroBooster array, quality control and imputation, preliminary analysis of ancestry composition, allele frequency calculation and association analysis was carried out for 294 samples. Results: The cohort consisted of 530 control participants and 470 PD patients, with a mean age of diagnosis of 59.9 ± 11.52 years. Among the PD patients, 21.2% were identified as having early-onset PD (NOTCH , LRRK2 , MTHFR and KPNA1 emerged as relevant to be prioritized in future studies. Conclusions: The MEX-PD consortium will contribute to the understanding of PD within the Mexican population. The data collected will enable a deeper comprehension of the specific contributions of genetic and environmental factors to these outcomes. Significance: This research advocates for the development of personalized treatments and aims to improve the quality of life for Mexican PD patients.

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 Parkinson’s 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 × 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.

Background: Juvenile‐onset Huntington's Disease (JoHD) or Huntington's disease (HD) with age of onset ≤20 years, is a rare clinical entity that often differs phenotypically from adult HD and represents only 1–15% of total HD cases.Objective: To characterize the genetic and clinical characteristics of 32 JoHD patients seen in a Peruvian Neurogenetics clinic from 2000–2018.Methods: This study is a retrospective clinical and genetic review. The clinical database in Lima, Peru was searched for HD patients seen in clinic between 2000 and 2018. Inclusion criteria were: (1) genetically confirmed disease; and (2) HD age of onset ≤20 years, according to the documented medical history.Results: Among 475 patients with genetically confirmed HD in the database, 32 patients (6.7%) had symptom onset at ≤20 years. Among JoHD patients with a known transmitting parent (30 of 32), paternal transmission accounted for 77% of cases. Anticipation was higher with paternal transmission compared to maternal transmission (27.5 ± 11.5 vs. 11.3 ± 7.1 years). Overall expanded CAG repeat length ranged from 44 to 110, with a mean length of 65.6 ± 15.4, and 14 (44%) cases had repeat length under 60. Of the 32 patients included in the study, 25 had detailed clinical symptomatology available, and many patients had unique clinical features such as prominent sleep disturbance (60% of patients), or parkinsonism (73%).Conclusions: This large case series of JoHD patients characterizes the Peruvian JoHD population, reports on unique familial relationships in JoHD, and highlights the varied symptomatic presentation of this rare disease.

Background: Parkinson's disease is the second most common neurodegenerative disorder and affects people from all ethnic backgrounds, yet little is known about the genetics of Parkinson's disease in non-European populations. In addition, the overall identification of copy number variants at a genome-wide level has been understudied in Parkinson's disease patients. Objectives: To understand the genome-wide burden of copy number variants in Latinos and its association with Parkinson's disease. Methods: We used genome-wide genotyping data from 747 Parkinson's disease patients and 632 ancestry matched controls from the Latin American Research Consortium on the Genetics of Parkinson's disease. Results: Genome-wide copy number burden analysis showed no difference between patients vs. controls, whereas patients were significantly enriched for copy number variants overlapping known Parkinson's disease genes compared to controls (Odds Ratio: 3.97 [1.69 - 10.5], P = 0.018). PARK2 showed the strongest copy number burden, with 20 copy number variant carriers. These patients presented an earlier age of disease onset compared to patients with other copy number variants (median age at onset: 31 years vs. 57 years, P = 7.46 x 10-7). Conclusions: We found that Parkinson's disease patients are significantly enriched with copy number variants affecting known Parkinson's disease genes. We also identified that out of 250 patients with early-onset disease, 5.6% carried a copy number variant on PARK2 in our cohort. Our study is the first to analyze genome-wide copy number variants association in Latino Parkinson's disease patients and provides insights about this complex disease in this understudied population.

The original version of this article unfortunately contained some mistakes in Table 2. The additional row (just above SCA2) with the following information