Search

Earlier findings of international comparisons on school achievement are often interpreted to mean that there is only a small percentage of excellent students in the Netherlands. Inspired by research in behaviour genetics, it was investigated whether Dutch high-scoring children are less sensitive to environmental influences than the non-high-scoring students. To test this, the reading and mathematics scores from high-scoring and non-high-scoring students participating in the Programme for International Student Achievement (PISA) 2012, the Trends in International Mathematics and Science Study (TIMSS) 2011 and the Progress in International Reading and Literacy Study (PIRLS) 2011 were analyzed. Contrary to our expectations, the results suggest that high-scoring children are as sensitive to school influences as are non-high-scoring students, but more sensitive to the influence of individual socioeconomic status.

Systemic as well as adipose tissue inflammation contributes to the development of obesity-associated diseases. This thesis describes three targets to battle this chronic inflammation in a model of diet-induced obesity in mice. First, we studied inflammation in obese white - and brown adipose tissue and whether the immune system contributes to adaptive thermogenesis. We show that short-term high-fat diet causes an accumulation of lipids, macrophages infiltration and pro-inflammatory cytokines and chemokines in brown adipose tissue. Furthermore, a high-fat diet leads to a rapid decline in eosinophils within both white - and brown adipose tissue. We identify an interesting crosstalk between immune cell cytokines and brown adipocyte derived chemokines, which is involved in the regulation of brown adipocyte activity. However, short-term treatment with helminth antigens in high-fat diet-fed mice induces an adipose depot-specific type 2 immune response which does not contribute to thermogenic activation. We then explored how the chronic low-grade inflammatory state in obesity and the continuous recruitment of immune cells affects hematopoietic stem cells in the bone marrow. Obesity induces long-term alterations on hematopoietic stem cells including loss of stemcellness, increased differentiation potential and reduced proliferation. Lastly, we demonstrate that inhibiting the interaction between the co-stimulatory molecule CD40 and its adaptor protein TRAF6 using a small-molecule inhibitor improves glucose tolerance and reduces adipose tissue immune cells in diet-induced obese mice.

The often-used ACE model which decomposes phenotypic variance into additive genetic (A), common-environmental (C) and unique-environmental (E) parts can be extended to include covariates. Collection of these variables however often leads to a large amount of missing data, for example when self-reports (e.g. questionnaires) are not fully completed. The usual approach to handle missing covariate data in twin research results in reduced power to detect statistical effects, as only phenotypic and covariate data of individual twins with complete data can be used. Here we present a full information approach to handle missing covariate data that makes it possible to use all available data. A simulation study shows that, independent of missingness scenario, number of covariates or amount of missingness, the full information approach is more powerful than the usual approach. To illustrate the new method, we applied it to test scores on a Dutch national school achievement test (Eindtoets Basisonderwijs) in the final grade of primary school of 990 twin pairs. The effects of school-aggregated measures (e.g. school denomination, pedagogical philosophy, school size) and the effect of the sex of a twin on these test scores were tested. None of the covariates had a significant effect on individual differences in test scores.