نبذة مختصرة : To investigate the biological etiology of human aggressive behavior through biomarker discovery and to explore the genetic etiology of variation in blood metabolite levels in humans, I analyzed twin-family data collected by the Netherlands Twin Register (NTR) and data of children referred to an academic centrum for child- and adolescent psychiatry. In my thesis, I argue for combining the classical twin design with genome-wide SNP (Single-Nucleotide Polymorphism) data to simultaneously estimate the total and SNP-based heritability. When analyzing 361 blood metabolites measured in a cohort of 5117 twin-family members, I applied this approach and found a stronger contribution of metabolite loci to lipids than to organic acids, and showed that the variance explained by metabolite loci differs significantly among metabolite classes and lipid species. These approaches based on measured SNPs are unsuitable for investigating the contribution of shared environmental factors. Therefore, I applied the classic twin design to 237 blood metabolite levels in 886 monozygotic (MZ) and 601 dizygotic (DZ) adult twin pairs, and reported significant estimates of the shared environment for only 6 out of 237 metabolites. To conclude, additive genetic factors contribute to approximately 50% of the individual variance in blood metabolites levels in adults. To look at aggression and biochemical biomarkers, I began with reviewing the existing literature for human aggression and related traits and found associations with biomarkers of multiple classes, including inflammation markers, neurotransmitters, lipoproteins, and thyroid and steroid hormones. However, I did not replicate the associations of lipid, inflammation, and related biomarkers with adult aggression in a twin-family cohort (N=5588), but found differences in glucose, fibrinogen, C-reactive protein, interleukin-6, and low-density lipoprotein cholesterol levels in the extremely discordant MZ twin pairs (12 pairs). I also tested the hypothesis that lipid CpG sites are ...
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