Identification of novel risk loci for restless legs syndrome in genome-wide association studies in individuals of European ancestry : a meta-analysis

Background Restless legs syndrome is a prevalent chronic neurological disorder with potentially severe mental and physical health consequences. Clearer understanding of the underlying pathophysiology is needed to improve treatment options. We did a meta-analysis of genome-wide association studies (GWASs) to identify potential molecular targets. Methods In the discovery stage, we combined three GWAS datasets (EU-RLS GENE, INTERVAL, and 23andMe) with diagnosis data collected from 2003 to 2017, in face-to-face interviews or via questionnaires, and involving 15126 cases and 95 725 controls of European ancestry. We identified common variants by fixed-effect inverse-variance meta-analysis. Significant genome-wide signals (p Findings We identified and replicated 13 new risk loci for restless legs syndrome and confirmed the previously identified six risk loci. MEIS1 was confirmed as the strongest genetic risk factor for restless legs syndrome (odds ratio 1.92, 95% CI 1 85-1.99). Gene prioritisation, enrichment, and genetic correlation analyses showed that identified pathways were related to neurodevelopment and highlighted genes linked to axon guidance (associated with SEMA6D), synapse formation (NTNG1), and neuronal specification (HOXB cluster family and MYT1). Interpretation Identification of new candidate genes and associated pathways will inform future functional research. Advances in understanding of the molecular mechanisms that underlie restless legs syndrome could lead to new treatment options. We focused on common variants; thus, additional studies are needed to dissect the roles of rare and structural variations.Peer reviewe

Evidence of causal effect of major depression on alcohol dependence: findings from the psychiatric genomics consortium

BACKGROUND Despite established clinical associations among major depression (MD), alcohol dependence (AD), and alcohol consumption (AC), the nature of the causal relationship between them is not completely understood. We leveraged genome-wide data from the Psychiatric Genomics Consortium (PGC) and UK Biobank to test for the presence of shared genetic mechanisms and causal relationships among MD, AD, and AC. METHODS Linkage disequilibrium score regression and Mendelian randomization (MR) were performed using genome-wide data from the PGC (MD: 135 458 cases and 344 901 controls; AD: 10 206 cases and 28 480 controls) and UK Biobank (AC-frequency: 438 308 individuals; AC-quantity: 307 098 individuals). RESULTS Positive genetic correlation was observed between MD and AD (rgMD−AD = + 0.47, P = 6.6 × 10−10). AC-quantity showed positive genetic correlation with both AD (rgAD−AC quantity = + 0.75, P = 1.8 × 10−14) and MD (rgMD−AC quantity = + 0.14, P = 2.9 × 10−7), while there was negative correlation of AC-frequency with MD (rgMD−AC frequency = −0.17, P = 1.5 × 10−10) and a non-significant result with AD. MR analyses confirmed the presence of pleiotropy among these four traits. However, the MD-AD results reflect a mediated-pleiotropy mechanism (i.e. causal relationship) with an effect of MD on AD (beta = 0.28, P = 1.29 × 10−6). There was no evidence for reverse causation. CONCLUSION This study supports a causal role for genetic liability of MD on AD based on genetic datasets including thousands of individuals. Understanding mechanisms underlying MD-AD comorbidity addresses important public health concerns and has the potential to facilitate prevention and intervention efforts

Breaking of Henry's law for noble gas and CO2 solubility in silicate melt under pressure

International audienc

Survival and Recovery Following Wildfire in the Southern Range of the Coast Redwood Forest

Fire plays a central role in determining structure, composition, and recruitment in many forest types. In coast redwood forests, the role of fire is not well understood and scant literature exists on post-fire response, particularly in the southern part of the range. In order to better understand patterns of survival and recruitment following fire for coast redwood (Sequoia sempervirens [lamb. ex D. Don] Endl.) and associated tree species, three sites in the Santa Cruz Mountains, California, USA, were sampled following wildfire. Randomly selected 10 m diameter plots were used to collect data on survivorship and post fire regeneration in order to analyze short-term responses including mortality, crown retention, basal sprouting, canopy regeneration, and seedling production. Results indicated that coast redwood had the lowest percent mortality (11.98 %) and highest mean canopy retention (43.10 %) of all species sampled, followed by Douglas-fir (Pseudotsuga menziesii [Mirb.] Franco) (25.54 %), tanoak (Notholithocarpus densiflorus [Hook. & Arn.] Manos) (23.27 %), combined oak species (Quercus sp.) (6.67 %), and Pacific madrone (Arbutus menziesii Pursh) (4.13 %). In addition, associated species experienced higher survival rates when proximate to coast redwoods. Coast redwood trees also exhibited the highest canopy regeneration (53 %), the highest average density of basal sprouts (3.54 × 104 ha), and the greatest average number of seedlings, ranging from zero to 2.09 × 105seedlings ha-1. Overall, coast redwood appeared to have a balance of fire adaptive features, exceeding all associated species, which allow individual trees to withstand fire, while at the same time promoting recruitment following fire