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

Impact of process intensification on a safe living environment

In de industrie worden in het proces- en installatieontwerp innovatieve benaderingen bedacht om grondstoffen en materialen efficiënter te gebruiken. Dat kan resulteren in aanzienlijk kleinere, schonere en meer energie-efficiënte technologie. Deze zogeheten procesintensificatie kan ook een manier zijn om industriële processen met gevaarlijke stoffen veiliger te maken. Het RIVM beschouwt 14 van deze procesintensificatie-technologieën als 'kansrijk' om omgevingsrisico's te verminderen. Het heeft hiervoor 69 wereldwijd ontwikkelde procesintensificatie-technologieën bekeken. De technologieën worden nog weinig in de praktijk gebruikt. Procesintensificatie kan op verschillende manieren de omgevingsrisico's verminderen. Het zou de kans op een ongeval kunnen verkleinen door de installatie veiliger te ontwerpen. Door de hoeveelheid gevaarlijke stoffen in de installatie te verminderen zijn de effecten van een ongeval op de omgeving bovendien kleiner. Verder zouden met procesintensificatie kleinere installaties kunnen worden gebouwd dicht bij producent of afnemer van de gevaarlijke stoffen. Door gevaarlijke stoffen minder te vervoeren, nemen de risico's voor de omgeving af. Een mogelijk nadeel van procesintensificatie kan zijn dat de procesvoering complexer wordt, waardoor risico's ook groter kunnen worden. Beleidsmakers kunnen de resultaten uit dit onderzoek van het RIVM gebruiken om instrumenten te ontwikkelen die risico's voor de omgeving voorkomen of verkleinen. Dit kan bijvoorbeeld door procesintensificatie-veiligheidsstudies te ondersteunen, of door eerste toepassingen in de praktijk te stimuleren. Ze kunnen bedrijven en toezichthouders er op wijzen dat procesintensificatie een manier is om de veiligheid bij risicovolle bedrijven continu te verbeteren. Dit onderzoek is uitgevoerd in opdracht van het ministerie van Infrastructuur en Waterstaat (IenW).Innovative approaches to the design of industrial processes and installations are being based on more efficient use of raw materials, and materials in general. It can lead to substantially smaller, cleaner and more energy efficient technology. This 'process intensification', as it is known, can also be used to make industrial processes involving dangerous goods safer. RIVM deems 14 of these process intensification technologies to be 'promising' when it comes to promoting a safe living environment. It looked at 69 globally-developed process intensification technologies before arriving at this conclusion. The application of these technologies is still limited. Process intensification can reduce environmental risks in different ways. By promoting the design of safer installations, it can lower the probability of accidents and by decreasing the quantity of dangerous goods in an installation, it can reduce the effects that accidents have on the environment. With process intensification, furthermore, smaller installations can be setup close to producers or end-users of dangerous goods. Environmental risks are reduced when dangerous goods are not transported. A disadvantage of process intensification is that it may make a process more complex or be more sensitive to process faults or deviations, so that the risks may also become greater. Policymakers can use the results of this research by RIVM to develop instruments that prevent, or reduce, these risks for the surroundings by, for example, supporting process intensification safety studies or by stimulating practical application. They can inform competent authorities that process intensification can be a way to continuously improve safety at high-risk companies. This research was commissioned by the Dutch Ministry of Infrastructure and Water Management (IenW).Ministerie van I&

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

BackgroundDespite 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.MethodsLinkage 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).ResultsPositive genetic correlation was observed between MD and AD (rg = + 0.47, P = 6.6 × 10 ). AC-quantity showed positive genetic correlation with both AD (rg = + 0.75, P = 1.8 × 10 ) and MD (rg = + 0.14, P = 2.9 × 10 ), while there was negative correlation of AC-frequency with MD (rg = -0.17, P = 1.5 × 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 ). There was no evidence for reverse causation.ConclusionThis 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