Year: 2018
Type: dissertation
Abstract: 2015).Although a moderate number of studies has been conducted, a meta-analysis including 12 candidate genes did not reveal any significant associations with aggressive behavior (Vassos et al., 2014).However, this meta-analysis might have suffered from the extensive heterogeneity of assessed phenotypes.A later meta-analysis, which investigated candidate variants in the SLC6A4 and MOAO genes specifically, did confirm association with antisocial behaviour (Ficks and Waldman, 2014).Specifically for the MAOA gene, more meta-analysic evidence for association of genetic variation with aggression is available.MAOA is an enzyme that breaks down monoamine neurotransmitters like serotonin and dopamine through oxidative deamination (Youdim and Bakhle, 2006).Meta-analysis showed significant interaction between MAOA genotype and environmental adversity, affecting antisocial behavior in a sex-dependent manner.Males with an allele of a common variable number tandem repeat (VNTR) polymorphism in the promoter region of this gene, causing low enzyme activity, appear to experience a stronger effect of maltreatment on antisocial behavior compared to males with the high activity variant.In females, an opposite and weaker effect of MAOA genotype was suggested by the data, with the high activity variant increasing risk for antisocial behavior after maltreatment (Byrd and Manuck, 2014;Caspi, 2002).The specific association pattern of this gene with aggression again nicely illustrates the heterogeneity issues discussed earlier in this introduction. IMAGE:The International Multicenter ADHD Genetics study was conducted by a consortium of seven European countries and Israel, with the aim to identify genetic risk factors for ADHD (Brookes et al., 2006; Muller et al., 2011a; Muller et al., 2011b).Families with at least one child with ADHD as well as at least one biological sibling (irrespective of ADHD diagnostic status) were recruited.IMAGE collected extensive phenotyping, neuropsychological and genotypic information of these families.The IMAGE project participated in the Genetic Association Information Network (GAIN) to enable genomewide genetic studies.In the Netherlands, it was followed-up by the NeuroIMAGE study, enriching the data-set with structural and functional MRI data, current clinical status, and additional collection of neuropsychological measures and DNA (von Rhein et al., 2015).IMpACT: The International Multicentre persistent ADHD CollaboraTion is a consortium of clinical and basic researchers from several European countries (The Netherlands, Germany, Spain, Norway, The United Kingdom, Sweden), from the United States of America, and from Brazil (www.impactadhdgenomics.com).The aim of IMpACT is to perform and promote high quality research in ADHD across the lifespan.It includes the identification of novel genetic variants for adult ADHD and improving the understanding the mechanisms underlying the effect of these genetic variants on disease risk.IMpACT currently coordinates biosamples and phenotypic information of over 4000 cases with persistent ADHD and over 8000 controls.In this thesis, data from Germany, Norway and Spain was used. BIG:The Brain Imaging Genetics study was set up in 2007 by the Human Genetics department of the Radboud university medical center and the Donders Centre for Cognitive Neuroimaging of the Radboud University (www.cognomics.nl/big).In 2010, the Max Planck Institute for Psycholinguistics in Nijmegen also joined.BIG aims to study relations between genes, brain structure and function, and cognition and behavior in healthy individuals.For this, a continuously growing database has been created with data of structural and functional magnetic resonance imaging (MRI)-based brain scans and DNA as well as cognitive and behavioral data derived from internet-based testing.ENIGMA: The Enhancing NeuroImaging Genetics through Meta Analysis network brings together researchers in imaging genomics to understand brain structure, function, and disease, based on brain imaging and genetic data (http://enigma.ini.usc.edu/).Currently, more than 30 working groups have been formed within the ENIGMA consortium.In this thesis, summary statistic data of the ENIGMA GWAS meta-analysis on subcortical volumes and intracranial volume is used (Hibar et al., 2015). EAGLE:The EArly Genetics and Lifecourse Epidemiology Consortium is a consortium of pregnancy and birth cohorts that aims to investigate the genetic basis of phenotypes in antenatal and early life and childhood.All participating cohorts have GWAS data available.In this thesis, summary statistic data of the EAGLE GWAS meta-analysis on childhood aggressiveness is used (Pappa et al., 2015).
Author: Marjolein M. J. van Donkelaar
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2809613971