Genetic variance and genotype reaction norms in response to larval food manipulation for a trait important in scorpionfly sperm competition.

Engqvist L. Genetic variance and genotype reaction norms in response to larval food manipulation for a trait important in scorpionfly sperm competition. Functional Ecology. 2008;22(1):070915213639001-???Sperm competition is an important attribute of many mating systems. Examining the genetic and environmental factors influencing male sperm competition success is essential in order to understand variation in reproductive success. In the scorpionfly Panorpa cognata, male success in sperm competition is influenced by the number of sperm transferred during copulation. This will be determined by copulation duration and the sperm transfer rate of males. Sperm transfer rate is a trait which shows considerable phenotypic variance. Here, I use a full-sib split-brood design in order to investigate both to what extent this trait is heritable and the influence of larval food availability on male sperm transfer rate. The results demonstrate considerable genetic variance underlying the phenotypic expression of sperm transfer rate. Heritability estimates were slightly larger, but not significantly so, for offspring reared at low food availability. In contrast, there was no straightforward evidence that larval food availability had an effect on the sperm transfer rate of males. However, a significant family x treatment interaction provided evidence of a genotype x environment effect on male sperm competitive ability. These results demonstrate different reaction norms for sperm transfer rate in response to larval treatment for individuals with different genetic background

Finding genetically-supported drug targets for Parkinson’s disease using Mendelian randomization of the druggable genome

Parkinson’s disease is a neurodegenerative movement disorder that currently has no disease-modifying treatment, partly owing to inefficiencies in drug target identification and validation. We use Mendelian randomization to investigate over 3,000 genes that encode druggable proteins and predict their efficacy as drug targets for Parkinson’s disease. We use expression and protein quantitative trait loci to mimic exposure to medications, and we examine the causal effect on Parkinson’s disease risk (in two large cohorts), age at onset and progression. We propose 23 drug-targeting mechanisms for Parkinson’s disease, including four possible drug repurposing opportunities and two drugs which may increase Parkinson’s disease risk. Of these, we put forward six drug targets with the strongest Mendelian randomization evidence. There is remarkably little overlap between our drug targets to reduce Parkinson’s disease risk versus progression, suggesting different molecular mechanisms. Drugs with genetic support are considerably more likely to succeed in clinical trials, and we provide compelling genetic evidence and an analysis pipeline to prioritise Parkinson’s disease drug development