Genetic Association Studies in Restless Legs Syndrome: Risk Variants & Ethnic Differences.

BACKGROUND: Genetic association studies have not produced consistent results in restless legs syndrome (RLS). OBJECTIVES: To conduct a systematic review on genetic association studies in RLS to highlight the common gene variants and ethnic differences. METHODOLOGY: We conducted Pubmed, Embase, and Cochrane search using terms "Genetic association studies" and "restless legs syndrome" for candidate gene-based studies. Out of the initial 43 studies, 18 case control studies (from 2012 to 2022) were included. Thirteen studies including 10794 Caucasian subjects (4984 RLS cases and 5810 controls) and five studies involving 2009 Asian subjects (796 RLS cases and 1213 controls) were tabulated and analyzed. In addition, three Genome-Wide Association Studies (GWAS) in Asians and Europeans/Caucasians were included for comparisons. RESULTS: In the Asian population, gene variants in BST1, SNCA Rep1, IL1B, BTBD9, and MAP2K5/SKOR1 increased the risk of RLS (odds ratio range 1.2-2.8). In Caucasian populations, examples of variants that were associated with an increased risk of RLS (odds ratio range 1.1-1.9) include those in GABRR3 TOX3, ADH1B, HMOX1, GLO1, DCDC2C, BTBD9, SKOR1, and SETBP1. Based on the meta-analysis of GWAS studies, the rs9390170 variant in UTRN gene was identified to be a novel genetic marker for RLS in Asian cohorts, whereas rs113851554 in MEIS1 gene was a strong genetic factor among the >20 identified gene variants for RLS in Caucasian populations. CONCLUSION: Our systemic review demonstrates that multiple genetic variants modulate risk of RLS in Caucasians (such as MEIS1 BTBD9, MAP2K5) and in Asians (such as BTBD9, MAP2K5, and UTRN).

Association between Type 1 Diabetes Mellitus and Parkinson's Disease: A Mendelian Randomization Study.

While much evidence suggests that type 2 diabetes mellitus increases the risk of Parkinson's disease (PD), the relationship between type 1 diabetes mellitus (T1DM) and PD is unclear. To study their association, we performed a two-sample Mendelian randomization (MR) using the following statistical methods: inverse variance weighting (IVW), MR-Egger, weight median, and weighted mode. Independent datasets with no sample overlap were retrieved from the IEU GWAS platform. All the MR methods found a lower risk of PD in T1DM (IVW-OR 0.93, 95% CI 0.91-0.96, p = 3.12 × 10-5; MR-Egger-OR 0.93, 95% CI 0.88-0.98, p = 1.45 × 10-2; weighted median-OR 0.93, 95% CI 0.89-0.98, p = 2.76 × 10-3; and weighted mode-OR 0.94, 95% CI 0.9-0.98, p = 1.58 × 10-2). The findings were then replicated with another independent GWAS dataset on T1DM (IVW-OR 0.97, 95% CI 0.95-0.99, p = 3.10 × 10-3; MR-Egger-OR 0.96, 95% CI 0.93-0.99, p = 1.08 × 10-2; weighted median-OR 0.97, 95% CI 0.94-0.99, p = 1.88 × 10-2; weighted mode-OR 0.97, 95% CI 0.94-0.99, p = 1.43 × 10-2). Thus, our study provides evidence that T1DM may have a protective effect on PD risk, though further studies are needed to clarify the underlying mechanisms.

Impact of COVID-19 pandemic on patients with Parkinson's disease: A meta-analysis of 13,878 patients.

BACKGROUND: The clinical, neuropsychological, and socioeconomic factors affecting Parkinson's disease (PD) during COVID-19 pandemic across different populations have not been systematically studied. To address this, we conducted a meta-analysis of factors that impact the well-being of PD patients during the pandemic. METHODS: Medline and Embase were searched for articles published between 2020 and 2022. We conducted random-effects pooling of estimates and meta-regression. RESULTS: Twenty-seven studies involving 13,878 patients from America, Europe, Asia, and Africa were included. There is a high prevalence of decreased physical activity and exercise, and worsening motor and neuropsychiatric symptoms (17-56%). Patients in lower-income countries more frequently reported worsening anxiety (adjusted OR [aOR] 8.94, 95% confidence interval [CI] 1.62-49.28, p = 0.012), sleep (aOR 5.16, 95% CI 1.15-23.17, p = 0.032), and PD symptoms (aOR 3.57, 95% CI 0.96-13.34, p = 0.058). Lockdown was associated with decreased exercise levels (aOR 0.13, 95% CI 0.02-0.78, p = 0.025) and worsening mood (aOR 0.48, 95% CI 0.24-0.95, p = 0.035). Younger age correlated with decreased physical activity (ß -0.30, 95% CI -0.53 to -0.07, p = 0.012), exercise (ß -0.11, 95% CI -0.15 to -0.07, p < 0.001), worsening PD symptoms (ß -0.08, 95% CI -0.15 to -0.01, p = 0.018), and sleep (ß -0.14, 95% CI -0.27 to 0, p = 0.044). Female PD patients reported a greater decrease in physical activity (ß 11.94, 95% CI 2.17-21.71, p = 0.017) and worse sleep (ß 10.76, 95% CI 2.81-18.70, p = 0.008). CONCLUSION: This large meta-analysis of PD patients in diverse populations identified a high prevalence of physical and mental worsening during the COVID-19 pandemic, with patients in lower-income countries being exceptionally vulnerable.