Heritability of Stroop and flanker performance in 12-year old children

BACKGROUND: There is great interest in appropriate phenotypes that serve as indicator of genetically transmitted frontal (dys)function, such as ADHD. Here we investigate the ability to deal with response conflict, and we ask to what extent performance variation on response interference tasks is caused by genetic variation. We tested a large sample of 12-year old monozygotic and dizygotic twins on two well-known and closely related response interference tasks; the color Stroop task and the Eriksen flanker task. Using structural equation modelling we assessed the heritability of several performance indices derived from those tasks. RESULTS: In the Stroop task we found high heritabilities of overall reaction time and – more important – Stroop interference (h(2 )= nearly 50 %). In contrast, we found little evidence of heritability on flanker performance. For both tasks no effects of sex on performance variation were found. CONCLUSIONS: These results suggest that normal variation in Stroop performance is influenced by underlying genetic variation. Given that Stroop performance is often hampered not only in people suffering from frontal dysfunction, but also in their unaffected relatives, we conclude that this variable may constitute a suitable endophenotype for future genetic studies. We discuss several reasons for the absence of genetic effects on the flanker task

Exploring the genetic correlations of antisocial behaviour and life history traits.

UNLABELLED: Prior evolutionary theory provided reason to suspect that measures of development and reproduction would be correlated with antisocial behaviours in human and non-human species. Behavioural genetics has revealed that most quantitative traits are heritable, suggesting that these phenotypic correlations may share genetic aetiologies. We use genome-wide association study data to estimate the genetic correlations between various measures of reproductive development (N = 52 776-318 863) and antisocial behaviour (N = 31 968). Our genetic correlation analyses demonstrate that alleles associated with higher reproductive output (number of children ever born, r g = 0.50, P = 0.0065) were positively correlated with alleles associated with antisocial behaviour, whereas alleles associated with more delayed reproductive onset (age at first birth, r g = -0.64, P = 0.0008) were negatively associated with alleles linked to antisocial behaviour. Ultimately, these findings coalesce with evolutionary theories suggesting that increased antisocial behaviours may partly represent a faster life history approach, which may be significantly calibrated by genes. DECLARATION OF INTEREST: None

Exploring the functional role of the CHRM2 gene in human cognition: results from a dense genotyping and brain expression study

<p>Abstract</p> <p>Background</p> <p>The <it>CHRM2 </it>gene, located on the long arm of chromosome 7 (7q31-35), is involved in neuronal excitability, synaptic plasticity and feedback regulation of acetylcholine release, and has been implicated in higher cognitive processing. The aim of this study is the identification of functional (non)coding variants underlying cognitive phenotypic variation.</p> <p>Methods</p> <p>We previously reported an association between polymorphisms in the 5'UTR regions of the <it>CHRM2 </it>gene and intelligence.. However, no functional variants within this area have currently been identified. In order to identify the relevant functional variant(s), we conducted a denser coverage of SNPs, using two independent Dutch cohorts, consisting of a children's sample (N = 371 ss; mean age 12.4) and an adult sample (N= 391 ss; mean age 37.6). For all individuals standardized intelligence measures were available. Subsequently, we investigated genotype-dependent <it>CHRM2 </it>gene expression levels in the brain, to explore putative enhancer/inhibition activity exerted by variants within the muscarinic acetylcholinergic receptor.</p> <p>Results</p> <p>Using a test of within-family association two of the previously reported variants – rs2061174, and rs324650 – were again strongly associated with intelligence (<it>P </it>< 0.01). A new SNP (rs2350780) showed a trend towards significance. SNP rs324650, is located within a short interspersed repeat (SINE). Although the function of short interspersed repeats remains contentious, recent research revealed potential functionality of SINE repeats in a gene-regulatory context. Gene-expression levels in post-mortem brain material, however were not dependent on rs324650 genotype.</p> <p>Conclusion</p> <p>Using a denser coverage of SNPs in the <it>CHRM2 </it>gene, we confirmed the 5'UTR regions to be most interesting in the context of intelligence, and ruled out other regions of this gene. Although no correlation between genomic variants and gene expression was found, it would be interesting to examine allele-specific effects on CHRM2 transcripts expression in much more detail, for example in relation to transcripts specific halve-life and their relation to LTP and memory.</p

Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use.

Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders1. They are heritable2,3 and etiologically related4,5 behaviors that have been resistant to gene discovery efforts6-11. In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association. Smoking phenotypes were positively genetically correlated with many health conditions, whereas alcohol use was negatively correlated with these conditions, such that increased genetic risk for alcohol use is associated with lower disease risk. We report evidence for the involvement of many systems in tobacco and alcohol use, including genes involved in nicotinic, dopaminergic, and glutamatergic neurotransmission. The results provide a solid starting point to evaluate the effects of these loci in model organisms and more precise substance use measures

The heritability and molecular genetics of mental disorders

People differ in their feelings, emotions, and behavior, and for centuries, scholars have been interested in the sources of this variation. Modern research in the last four decades, using family and twin designs, has shown that variation in mental health and disorders is explained by both genetic and environmental variation. The influence of genetic variation (i.e., heritability) on mental disorders differs. Neurodevelopmental disorders are among the most heritable disorders while internalizing disorders, like major depressive disorder, show lower heritability estimates. Genome-wide association studies (GWAS) are used to search the whole genome for associations between genetic variants and mental disorders. These analyses have resulted in multiple associations between particular genetic variants and mental disorders; however, genetic variants explain only a relatively small proportion of variation in mental disorders, and more research is needed to unravel their biological function. GWAS results confirmed that different mental disorders have many genetic variants in common, which may explain the co-occurrence of mental disorders and the overlap in disorder symptoms that is often observed. Finally, GWAS results can be used to obtain polygenic scores that provide an indication of the degree of genetic risk for mental disorders that may become of clinical utility in the near future

No differences between adults with and without autism in audiovisual synchrony perception

LAY ABSTRACT: It has been known for a long time that individuals diagnosed with autism spectrum disorder perceive the world differently. In this study, we investigated how people with or without autism perceive visual and auditory information. We know that an auditory and a visual stimulus do not have to be perfectly synchronous for us to perceive them as synchronous: first, when the two are within a certain time window (temporal binding window), the brain will tell us that they are synchronous. Second, the brain can also adapt quickly to audiovisual asynchronies (rapid recalibration). Although previous studies have shown that people with autism spectrum disorder have different temporal binding windows, and less rapid recalibration, we did not find these differences in our study. However, we did find that both processes develop over age, and since previous studies tested only young people (children, adolescents, and young adults), and we tested adults from 18 to 55 years, this might explain the different findings. In the end, there might be quite a complex story, where people with and without autism spectrum disorder perceive the world differently, even dependent on how old they are