General population normative scores for interpreting the BODY-Q

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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.

BACKGROUND: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. RESULTS: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. CONCLUSIONS: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk

Broadening the debate on shale gas : guidelines for decision-making based on the Dutch experience

This paper focuses on the debate on shale gas in the Netherlands. In the political decision-making process relating to shale gas, the national government has highlighted the importance of clarifying the opportunities and risks related to shale gas extraction, and the question of whether this is properly regulated. This has given rise to a study commissioned by the Ministry of Economic Affairs aimed at investigating whether shale gas can be safely extracted in the Netherlands. (In the remainder of this paper this study will be referred to as the so-called ‘risk and safety’ study). The Rathenau Instituut found that the focus of the ‘risk and safety’ study was out of sync with the political and public debate about shale gas extraction in the Netherlands. For example, a media analysis showed that, besides safety risks and environmental risks, the debate also focused on how the role of shale gas extraction worldwide affects the Netherlands, as well as on local support (Waes, 2013). Also various members of parliament stressed the need for a broader debate, including the national usefulness and necessity of shale gas extraction, and the location-specific aspects relating to this issue