Gene-Environment Interactions for Parkinson's Disease.

OBJECTIVE: Parkinson's disease (PD) is a neurodegenerative disorder with complex etiology. Multiple genetic and environmental factors have been associated with PD, but most PD risk remains unexplained. The aim of this study was to test for statistical interactions between PD-related genetic and environmental exposures in the 23andMe, Inc. research dataset. METHODS: Using a validated PD polygenic risk score and common PD-associated variants in the GBA gene, we explored interactions between genetic susceptibility factors and 7 lifestyle and environmental factors: body mass index (BMI), type 2 diabetes (T2D), tobacco use, caffeine consumption, pesticide exposure, head injury, and physical activity (PA). RESULTS: We observed that T2D, as well as higher BMI, caffeine consumption, and tobacco use, were associated with lower odds of PD, whereas head injury, pesticide exposure, GBA carrier status, and PD polygenic risk score were associated with higher odds. No significant association was observed between PA and PD. In interaction analyses, we found statistical evidence for an interaction between polygenic risk of PD and the following environmental/lifestyle factors: T2D (p = 6.502 × 10-8), PA (p = 8.745 × 10-5), BMI (p = 4.314 × 10-4), and tobacco use (p = 2.236 × 10-3). Although BMI and tobacco use were associated with lower odds of PD regardless of the extent of individual genetic liability, the direction of the relationship between odds of PD and T2D, as well as PD and PA, varied depending on polygenic risk score. INTERPRETATION: We provide preliminary evidence that associations between some environmental and lifestyle factors and PD may be modified by genotype. ANN NEUROL 2024;95:677-687.

Association Between Postdischarge Medical Oncology Follow-Up Appointments and Downstream Health Care Use: A Single-Institution Experience.

PURPOSE: There is limited understanding of the role of postdischarge medical oncology follow-up during care transition periods. Our study describes the care transition patterns and the association between postdischarge medical oncology appointments and downstream health care use at a tertiary academic center. METHODS: We conducted a retrospective cohort study of 25,135 medical oncology admissions between 2018 and 2020 at Yale New Haven Hospital. We examined the association between postdischarge medical oncology appointment timing with 30-day all-cause readmissions and emergency department (ED) visits using multivariable logistic regression models and propensity score-matched analyses. RESULTS: Compared with admissions without appointment within 30 days, admissions with postdischarge medical oncology appointment within 30 days were associated with lower rates of all-cause 30-day readmission (odds ratio [OR] = 0.56, 95% CI, 0.52 to 0.59; P < .001) and ED visit (OR = 0.56, 95% CI, 0.52 to 0.59; P < .001). Admissions with appointment ≤ 14 days were associated with lower rates of 30-day readmission (OR = 0.28, 95% CI, 0.25 to 0.32; P < .001) and ED visit (OR = 0.56, 95% CI, 0.52 to 0.63; P < .001) compared with those with appointment within 15-30 days. Similar patterns in health care use were seen with propensity score matching. Subgroup analyses of cancer types with the most admissions observed similar trends between 30-day readmission and ED visits with appointment timing. CONCLUSION: Timely postdischarge medical oncology appointments were associated with significantly lower likelihood of 30-day readmission and ED visits, suggesting a potential role for postdischarge follow-up as an intervention to decrease health care use.