Genome-wide association and Meta-analysis of age at onset in Parkinson Disease

Background and Objectives Considerable heterogeneity exists in the literature concerning genetic determinants of the age at onset (AAO) of Parkinson disease (PD), which could be attributed to a lack of well-powered replication cohorts. The previous largest genome-wide association studies (GWAS) identified SNCA and TMEM175 loci on chromosome (Chr) 4 with a significant influence on the AAO of PD; these have not been independently replicated. This study aims to conduct a meta-analysis of GWAS of PD AAO and validate previously observed findings in worldwide populations. Methods A meta-analysis was performed on PD AAO GWAS of 30 populations of predominantly European ancestry from the Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson's Disease (COURAGE-PD) Consortium. This was followed by combining our study with the largest publicly available European ancestry dataset compiled by the International Parkinson Disease Genomics Consortium (IPDGC). Results The COURAGE-PD Consortium included a cohort of 8,535 patients with PD (91.9%: Europeans and 9.1%: East Asians). The average AAO in the COURAGE-PD dataset was 58.9 years (SD = 11.6), with an underrepresentation of females (40.2%). The heritability estimate for AAO in COURAGE-PD was 0.083 (SE = 0.057). None of the loci reached genome-wide significance (p < 5 × 10−8). Nevertheless, the COURAGE-PD dataset confirmed the role of the previously published TMEM175 variant as a genetic determinant of the AAO of PD with Bonferroni-corrected nominal levels of significance (p < 0.025): (rs34311866: β(SE)COURAGE = 0.477(0.203), pCOURAGE = 0.0185). The subsequent meta-analysis of COURAGE-PD and IPDGC datasets (Ntotal = 25,950) led to the identification of 2 genome-wide significant association signals on Chr 4, including the previously reported SNCA locus (rs983361: β(SE)COURAGE+IPDGC = 0.720(0.122), pCOURAGE+IPDGC = 3.13 × 10−9) and a novel BST1 locus (rs4698412: β(SE)COURAGE+IPDGC = −0.526(0.096), pCOURAGE+IPDGC = 4.41 × 10−8). Discussion Our study further refines the genetic architecture of Chr 4 underlying the AAO of the PD phenotype through the identification of BST1 as a novel AAO PD locus. These findings open a new direction for the development of treatments to delay the onset of PD

Somatosensory modulation of perceptual vestibular detection

Vestibular-multisensory interactions are essential for self-motion, navigation and postural stability. Despite evidence suggesting shared brain areas between vestibular and somatosensory inputs, no study has yet investigated whether somatosensory information influences vestibular perception. Here, we used signal detection methods to identify whether somatosensory stimulation might interact with vestibular events in a vestibular detection task. Participants were instructed to detect near-threshold vestibular roll-rotation sensations delivered by galvanic vestibular stimulation in one-half of experimental trials. A vibrotactile signal occurred to the index fingers of both hands in half of the trials, independent of vestibular signals. We found that vibrotactile somatosensory stimulation decreased perceptual vestibular sensitivity. The results are compatible with a gain regulation mechanism between vestibular and somatosensory modalities

Investigation of Shared Genetic Risk Factors Between Parkinson's Disease and Cancers

Background Epidemiological studies that examined the association between Parkinson's disease (PD) and cancers led to inconsistent results, but they face a number of methodological difficulties. Objective We used results from genome-wide association studies (GWASs) to study the genetic correlation between PD and different cancers to identify common genetic risk factors. Methods We used individual data for participants of European ancestry from the Courage-PD (Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson's Disease; PD, N = 16,519) and EPITHYR (differentiated thyroid cancer, N = 3527) consortia and summary statistics of GWASs from iPDGC (International Parkinson Disease Genomics Consortium; PD, N = 482,730), Melanoma Meta-Analysis Consortium (MMAC), Breast Cancer Association Consortium (breast cancer), the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (prostate cancer), International Lung Cancer Consortium (lung cancer), and Ovarian Cancer Association Consortium (ovarian cancer) (N comprised between 36,017 and 228,951 for cancer GWASs). We estimated the genetic correlation between PD and cancers using linkage disequilibrium score regression. We studied the association between PD and polymorphisms associated with cancers, and vice versa, using cross-phenotypes polygenic risk score (PRS) analyses. Results We confirmed a previously reported positive genetic correlation of PD with melanoma (Gcorr = 0.16 [0.04; 0.28]) and reported an additional significant positive correlation of PD with prostate cancer (Gcorr = 0.11 [0.03; 0.19]). There was a significant inverse association between the PRS for ovarian cancer and PD (odds ratio [OR] = 0.89 [0.84; 0.94]). Conversely, the PRS of PD was positively associated with breast cancer (OR = 1.08 [1.06; 1.10]) and inversely associated with ovarian cancer (OR = 0.95 [0.91; 0.99]). The association between PD and ovarian cancer was mostly driven by rs183211 located in an intron of the NSF gene (17q21.31). Conclusions We show evidence in favor of a contribution of pleiotropic genes to the association between PD and specific cancers. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA

Monitoring of climate change in Germany – data, products and services of Germany's National Climate Data Centre

Germany's national meteorological service (Deutscher Wetterdienst, DWD) is the responsible authority for monitoring climate change in Germany. To fulfill this task it operates the National Climate Data Centre ("Nationales KlimaDatenZentrum, NKDZ"). The historical and current instrumental measurements and visual observations of DWD's station network are archived, quality-controlled and used to provide aggregated products, as for example daily and monthly means or climate normals. Gridded data are generated and used to derive time series of national and regional averages. Phenological observations and radiosonde data are also part of the data base. <br><br> In recent years, additional historical data have been digitized to expand the data base. The products are used for informing the public, e.g. as an element of the German climate atlas (<a href="http://www.deutscher-klimaatlas.de"target="_blank">http://www.deutscher-klimaatlas.de</a>). One major recent activity was the provision of information for the new climatological reference interval 1981–2010 and an updated climatological analysis based on the newly digitized data

Sensitivity of Human Visual and Vestibular Cortical Regions to Egomotion-Compatible Visual Stimulation

The analysis and representation of visual cues to self-motion (egomotion) is primarily associated with cortical areas MST, VIP, and (recently) cingulate sulcus visual area (CSv). Various other areas, including visual areas V6 and V6A, and vestibular areas parietoinsular vestibular cortex (PIVC), putative area 2v (p2v), and 3aNv, are also potentially suited to processing egomotion (in some cases based on multisensory cues), but it is not known whether they are in fact involved in this process. In a functional magnetic resonance imaging (fMRI) experiment, we presented human participants with 2 types of random dot kinematograms. Both contained coherent motion but one simulated egomotion while the other did not. An area in the parieto-occipital sulcus that may correspond to V6, PIVC, and p2v were all differentially responsive to egomotion-compatible visual stimuli, suggesting that they may be involved in encoding egomotion. More generally, we show that the use of such stimuli provides a simple and reliable fMRI localizer for human PIVC and p2v, which hitherto required galvanic or caloric stimulation to be identified