Increasing the power of genome wide association studies in natural populations using repeated measures : evaluation and implementation

1. Genomewide association studies (GWAS) enable detailed dissections of the genetic basis for organisms' ability to adapt to a changing environment. In long-term studies of natural populations, individuals are often marked at one point in their life and then repeatedly recaptured. It is therefore essential that a method for GWAS includes the process of repeated sampling. In a GWAS, the effects of thousands of single-nucleotide polymorphisms (SNPs) need to be fitted and any model development is constrained by the computational requirements. A method is therefore required that can fit a highly hierarchical model and at the same time is computationally fast enough to be useful. 2. Our method fits fixed SNP effects in a linear mixed model that can include both random polygenic effects and permanent environmental effects. In this way, the model can correct for population structure and model repeated measures. The covariance structure of the linear mixed model is first estimated and subsequently used in a generalized least squares setting to fit the SNP effects. The method was evaluated in a simulation study based on observed genotypes from a long-term study of collared flycatchers in Sweden. 3. The method we present here was successful in estimating permanent environmental effects from simulated repeated measures data. Additionally, we found that especially for variable phenotypes having large variation between years, the repeated measurements model has a substantial increase in power compared to a model using average phenotypes as a response. 4. The method is available in the R package RepeatABEL. It increases the power in GWAS having repeated measures, especially for long-term studies of natural populations, and the R implementation is expected to facilitate modelling of longitudinal data for studies of both animal and human populations.

Estimation of genetic variance for macro- and micro-environmental sensitivity using double hierarchical generalized linear models

Background: Genetic variation for environmental sensitivity indicates that animals are genetically different in their response to environmental factors. Environmental factors are either identifiable (e.g. temperature) and called macro-environmental or unknown and called micro-environmental. The objectives of this study were to develop a statistical method to estimate genetic parameters for macro- and micro-environmental sensitivities simultaneously, to investigate bias and precision of resulting estimates of genetic parameters and to develop and evaluate use of Akaike’s information criterion using h-likelihood to select the best fitting model. Methods: We assumed that genetic variation in macro- and micro-environmental sensitivities is expressed as genetic variance in the slope of a linear reaction norm and environmental variance, respectively. A reaction norm model to estimate genetic variance for macro-environmental sensitivity was combined with a structural model for residual variance to estimate genetic variance for micro-environmental sensitivity using a double hierarchical generalized linear model in ASReml. Akaike’s information criterion was constructed as model selection criterion using approximated h-likelihood. Populations of sires with large half-sib offspring groups were simulated to investigate bias and precision of estimated genetic parameters. Results: Designs with 100 sires, each with at least 100 offspring, are required to have standard deviations of estimated variances lower than 50% of the true value. When the number of offspring increased, standard deviations of estimates across replicates decreased substantially, especially for genetic variances of macro- and micro-environmental sensitivities. Standard deviations of estimated genetic correlations across replicates were quite large (between 0.1 and 0.4), especially when sires had few offspring. Practically, no bias was observed for estimates of any of the parameters. Using Akaike’s information criterion the true genetic model was selected as the best statistical model in at least 90% of 100 replicates when the number of offspring per sire was 100. Application of the model to lactation milk yield in dairy cattle showed that genetic variance for micro- and macro-environmental sensitivities existed. Conclusion: The algorithm and model selection criterion presented here can contribute to better understand genetic control of macro- and micro-environmental sensitivities. Designs or datasets should have at least 100 sires each with 100 offspring.

Flipped classroom and learning strategies

This paper seeks to answer the research question "How does the flipped classroom affect students’ learning strategies?" In e-learning research, several studies have focused on how students and teachers perceive the flipped classroom approach. In general, these studies have reported pleasing results. Nonetheless, few, if any, studies have attempted to find out the potential effects of the flipped classroom approach on how students learn. This study was based on two cases: 1) a business modelling course and 2) a research methodology course. In both cases, participating students were from information systems courses at Dalarna University in Sweden. Recorded lectures replaced regular lectures. The recorded lectures were followed by seminars that focused on the learning content of each lecture in various ways. Three weeks after the final seminar, we arranged for two focus group interviews to take place in each course, with 8 to 10 students participating in each group. We asked open questions on how the students thought they had been affected and more dedicated questions that were generated from a literature study on the effects of flipped classroom courses. These questions dealt with issues about mobility, the potential for repeating lectures, formative feedback, the role of seminars, responsibility, empowerment, lectures before seminars, and any problems encountered. Our results show that, in general, students thought differently about learning after the courses in relation to more traditional approaches, especially regarding the need to be more active. Most students enjoyed the mobility aspect and the accessibility of recorded lectures, although a few claimed it demanded a more disciplined attitude. Most students also expressed a feeling of increased activity and responsibility when participating in seminars. Some even felt empowered because they could influence seminar content. The length of and possibility to navigate in recorded lectures was also considered important. The arrangement of the seminar rooms should promote face-to-face discussions. Finally, the types of questions and tasks were found to affect the outcomes of the seminars. The overall conclusion with regard to students’ learning strategies is that to be an active, responsible, empowered, and critical student you have to be an informed student with possibilities and mandate to influence how, where and when to learn and be able to receive continuous feedback during the learning process. Flipped classroom can support such learning.