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Biology subjects

Johnson, M. B.

Publications and source records attributed to Johnson, M. B..

2 recordsLinked to original sources

Correlates of cannabinoid concentrations, real-world driving, and driving-related skills

Research on the relationship between cannabis use and safe driving has produced mixed results. Most studies have focused exclusively on the presence or concentration of delta-9-tetrahydrocannabinol (THC), the primary psychoactive ingredient in the drug. However, cannabis is a complex substance, and both toxicological research and user experience suggests that some cannabis strains--often those with at least moderate levels of cannabidiol (CBD)-- produce a different, more sedating \"high\" than cannabis strains with no or low levels of CBD. We hypothesize that the sedating properties of some high-CBD cannabis strains has potential to impair driving and driving-related skills above and beyond the effects of THC intoxication. Three studies--one instrumented vehicle driving study and two laboratory-style epidemiological studies--examined real driving and computerized task performance as a function THC and CBD concentrations (and their interactions). In all three studies, higher CBD levels predicted greater impairment. There was relatively little evidence of impairment when CBD was zero, even at high THC levels. The results suggest that THC concentrations alone are not sufficient to predict impairment due to cannabis use. Results are interpreted in the context of drug tolerance.

epidemiology

Heterozygous RFX6 protein truncating variants cause Maturity-Onset Diabetes of the Young (MODY) with reduced penetrance

Finding new genetic causes of monogenic diabetes can help to understand development and function of the human pancreas. We aimed to find novel protein-truncating variants causing Maturity-Onset Diabetes of the Young (MODY), a subtype of monogenic diabetes. We used a combination of next-generation sequencing of MODY cases with unknown aetiology along with comparisons to the ExAC database to identify new MODY genes. In the discovery cohort of 36 European patients, we identified two probands with novel RFX6 heterozygous nonsense variants. RFX6 protein truncating variants were enriched in the MODY discovery cohort compared to the European control population within ExAC (odds ratio, OR=131, P=lxl0-4). We found similar results in non-Finnish European (n=348, OR=43, P=5xl0-5) and Finnish (n=80, OR=22, P=1xl0-6) replication cohorts. The overall meta-analysis OR was 34 (P=lxl0-16). RFX6 heterozygotes had reduced penetrance of diabetes compared to common HNF1A and HNF4A-MODY mutations (27%, 70% and 55% at 25 years of age, respectively). The hyperglycaemia resulted from beta-cell dysfunction and was associated with lower fasting and stimulated gastric inhibitory polypeptide (GIP) levels. Our study demonstrates that heterozygous RFX6 protein truncating variants are associated with MODY with reduced penetrance.

genetics