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Background: The use of illicit substances is correlated, meaning that individuals who use one illicit substance are more likely to also use another illicit substance. This association could (partly) be explained by overlapping genetic factors. Genetic overlap may indicate a common underlying genetic predisposition, or can be the result of a causal association., Methods: Polygenic scores for lifetime cannabis use were generated in a sample of Dutch participants (N = 8348). We tested the association of a PGS for cannabis use with ecstasy, stimulants and a broad category of illicit drug use. To explore the nature of the relationship: (1) these analyses were repeated separately in cannabis users and non-users and (2) monozogytic twin pairs discordant for cannabis use were compared on their drug use., Results: The lifetime prevalence was 24.8 % for cannabis, 6.2 % for ecstasy, 6.5 % for stimulants and 7.1 % for any illicit drug use. Significant, positive associations were found between PGS for cannabis use with ecstasy use, stimulants and any illicit drug use. These associations seemed to be stronger in cannabis users compared to non-users for both ecstasy and stimulant use, but only in people born after 1968 and not significant after correction for multiple testing. The discordant twin pair analyses suggested that cannabis use could play a causal role in drug use., Conclusions: The genetic liability underlying cannabis use significantly explained variability in ecstasy, stimulant and any illicit drug use. Further research should further explore the underlying mechanism to understand the nature of the association., Competing Interests: Declaration of Competing Interest No conflict declared., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Human DNA polymorphisms vary across geographic regions, with the most commonly observed variation reflecting distant ancestry differences. Here we investigate the geographic clustering of common genetic variants that influence complex traits in a sample of ~450,000 individuals from Great Britain. Of 33 traits analysed, 21 showed significant geographic clustering at the genetic level after controlling for ancestry, probably reflecting migration driven by socioeconomic status (SES). Alleles associated with educational attainment (EA) showed the most clustering, with EA-decreasing alleles clustering in lower SES areas such as coal mining areas. Individuals who leave coal mining areas carry more EA-increasing alleles on average than those in the rest of Great Britain. The level of geographic clustering is correlated with genetic associations between complex traits and regional measures of SES, health and cultural outcomes. Our results are consistent with the hypothesis that social stratification leaves visible marks in geographic arrangements of common allele frequencies and gene-environment correlations.

Background: Because of practice variation and new developments in palliative pediatric care, the Dutch Association of Pediatrics decided to develop the clinical practice guideline (CPG) palliative care for children. With this guideline, the association also wanted to precipitate an attitude shift towards shared decision-making (SDM) and therefore integrated SDM in the CPG Palliative care for children. The aim was to gain insight if integrating SDM in CPGs can potentially encourage pediatricians to practice SDM. Its objectives were to explore pediatricians' attitudes and thoughts regarding (1) recommendations on SDM in CPGs in general and the guideline Palliative care for children specifically; (2) other SDM enhancing strategies or tools linked to CPGs., Methods: Semi-structured face-to-face interviews. Pediatricians (15) were recruited through purposive sampling in three university-based pediatric centers in the Netherlands. The interviews were audio-recorded and transcribed verbatim, coded by at least two authors and analyzed with NVivo., Results: Some pediatricians considered SDM a skill or attitude that cannot be addressed by clinical practice guidelines. According to others, however, clinical practice guidelines could enhance SDM. In case of the guideline Palliative care for children, the recommendations needed to focus more on how to practice SDM, and offer more detailed recommendations, preferring a recommendation stating multiple options. Most interviewed pediatricians felt that patient decisions aids were beneficial to patients, and could ensure that all topics relevant to the patient are covered, even topics the pediatrician might not consider him or herself, or deems less important. Regardless of the perceived benefit, some pediatricians preferred providing the information themselves instead of using a patient decision aid., Conclusions: For clinical practice guidelines to potentially enhance SDM, guideline developers should avoid blanket recommendations in the case of preference sensitive choices, and SDM should not be limited to recommendations on non-treatment decisions. Furthermore, preference sensitive recommendations are preferably linked with patient decision aids.