Missing heritability is a common problem in psychiatry that impedes precision medicine approaches to autism and other heritable complex disorders. This proof-of-concept study uses a systematic... Show moreMissing heritability is a common problem in psychiatry that impedes precision medicine approaches to autism and other heritable complex disorders. This proof-of-concept study uses a systematic review and meta-analysis of the association between variants of the serotonin transporter promoter (5-HTTLPR) and autism to explore the hypothesis that some missing heritability can be explained using an optimum curve. A systematic literature search was performed to identify transmission disequilibrium tests on the short/long (S/L) 5-HTTLPR polymorphism in relation to autism. We analysed five American, seven European, four Asian and two American/European samples. We found no transmission preference in the joint samples and in Europe, preferential transmission of S in America and preferential transmission of L in Asia. Heritability will be underestimated or missed in genetic association studies if two alternative genetic variants are associated with the same disorder in different subsets of a sample. An optimum curve, relating a multifactorial biological variable that incorporates genes and environment to a score for a human trait, such as social competence, can explain this. We suggest that variants of functionally related genes will sometimes appear in fixed combinations at both sides of an optimum curve and propose that future association studies should account for such combinations. Show less
Heijungs, R.; Koning, A. de; Wegener Sleeswijk, A. 2015
Sustainability research has entered an era of data abundance, in which online repositories offer millions of facts on production, consumption, pollution, and impacts. The combination of such facts... Show moreSustainability research has entered an era of data abundance, in which online repositories offer millions of facts on production, consumption, pollution, and impacts. The combination of such facts in linear models leads increasingly to computational problems, relating to memory, speed, accuracy, and stability. This paper examines this phenomenon from the perspective of three widely-used types of sustainability analysis: multimedia fate and exposure models, life cycle assessment of products, and environmentally extended input-output analysis. The paper describes the various theoretical arguments, some indicators, and some solutions. Moreover, it adds the empirical evidence from one of these analysis types, namely life cycle assessment. It concludes that the phenomena indeed occur in practice, that abstract indicators ignore the subtle differences between different types of environmental impacts, and that a sound strategy for dealing with these problems is the critical analysis of results together with the variation of the computational principles. Show less
Environmental life cycle assessment (LCA) is a method for the quantitative assessment of the environmental impacts of products. A number of impact categories are related to toxic effects of... Show moreEnvironmental life cycle assessment (LCA) is a method for the quantitative assessment of the environmental impacts of products. A number of impact categories are related to toxic effects of chemicals. Multimedia models for substance fate, supplemented with models for human exposure, have been developed in the context of human and environmental risk assessment (HERA). Different authors have adapted such models for use in LCA, largely on a continental level. It has sometimes been suggested to merge LCA toxicity assessment and HERA into one common tool. Here, it is demonstrated that LCA and HERA cannot be merged, due to a fundamental difference concerning their respective goals. Subsequently, adaptations to existing multimedia models are proposed to make it possible to extend multimedia models with a module for metals. The core of the thesis is formed by the GLOBOX model: a global, regionally differentiated fate, intake and effect model for LCA toxicity assessment. For emissions of any organic chemical or metal to any compartment in any country or at any sea, this model calculates region-specific characterisation factors. Finally, an updated set of LCA normalisation factors is provided, with which the relative contributions of a product to the different impact categories can be evaluated. Show less
Guinée, J.B.; Heijungs, R.; Kleijn, R.; Voet, E. van der; Koning, A. de; Oers, L. van; ... ; Wegener Sleeswijk, A. 2006
