Controlling the charge transfer flow at the graphene/pyrene-nitrilotriacetic acid interface

The fabrication of highly efficient bio-organic nanoelectronic devices is still a challenge due to the difficulty in interfacing the biomolecular component to the organic counterparts. One of the ways to overcome this bottleneck is to add a self-assembled monolayer (SAM) in between the electrode and the biological material. The addition of a pyrene-nitrilotriacetic acid layer to a graphene metal electrode enhances the charge transfer within the device. Our theoretical calculations and electrochemical results show that the formation of a pyrene-nitrilotriacetic acid SAM enforces a direct electron transfer from graphene to the SAM, while the addition of the Ni2+ cation and imidazole reverses the charge transfer direction, allowing an atomic control of the electron flow, which is essential for a true working device. © 2018 The Royal Society of Chemistry

Finding class C GPCR subtype-discriminating n-grams through feature selection

G protein-coupled receptors (GPCRs) are a large and heterogeneous superfamily of receptors that are key cell players for their role as extracellular signal transmitters. Class C GPCRs, in particular, are of great interest in pharmacology. The lack of knowledge about their full 3-D structure prompts the use of their primary amino acid sequences for the construction of robust classifiers, capable of discriminating their different subtypes. In this paper, we describe the use of feature selection techniques to build Support Vector Machine (SVM)-based classification models from selected receptor subsequences described as n-grams. We show that this approach to classification is useful for finding class C GPCR subtype-specific motifs.Peer ReviewedPostprint (author’s final draft

Pleiotropy across academic subjects at the end of compulsory education.

Research has shown that genes play an important role in educational achievement. A key question is the extent to which the same genes affect different academic subjects before and after controlling for general intelligence. The present study investigated genetic and environmental influences on, and links between, the various subjects of the age-16 UK-wide standardized GCSE (General Certificate of Secondary Education) examination results for 12,632 twins. Using the twin method that compares identical and non-identical twins, we found that all GCSE subjects were substantially heritable, and that various academic subjects correlated substantially both phenotypically and genetically, even after controlling for intelligence. Further evidence for pleiotropy in academic achievement was found using a method based directly on DNA from unrelated individuals. We conclude that performance differences for all subjects are highly heritable at the end of compulsory education and that many of the same genes affect different subjects independent of intelligence

Genome-wide association study of receptive language ability of 12 year olds

Purpose: We have previously shown that individual differences in measures of receptive language ability at age 12 are highly heritable. The current study attempted to identify some of the genes responsible for the heritability of receptive language ability using a genome-wide association (GWA) approach. Method: We administered four internet-based measures of receptive language (vocabulary, semantics, syntax, and pragmatics) to a sample of 2329 12-year-olds for whom DNA and genome-wide genotyping were available. Nearly 700,000 single-nucleotide polymorphisms (SNPs) and one million imputed SNPs were included in a GWA analysis of receptive language composite scores. Results: No SNP associations met the demanding criterion of genome-wide significance that corrects for multiple testing across the genome (p < 5 ×10-8). The strongest SNP association did not replicate in an additional sample of 2639 12-year-olds. Conclusion: These results indicate that individual differences in receptive language ability in the general population do not reflect common genetic variants that account for >3% of the phenotypic variance. The search for genetic variants associated with language skill will require larger samples and additional methods to identify and functionally characterize the full spectrum of risk variants

Common Genetic Variants Explain the Majority of the Correlation Between Height and Intelligence : The Generation Scotland Study

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Differences in exam performance between pupils attending selective and non-selective schools mirror the genetic differences between them

On average, students attending selective schools outperform their non-selective counterparts in national exams. These differences are often attributed to value added by the school, as well as factors schools use to select pupils, including ability, achievement and, in cases where schools charge tuition fees or are located in affluent areas, socioeconomic status. However, the possible role of DNA differences between students of different schools types has not yet been considered. We used a UK-representative sample of 4814 genotyped students to investigate exam performance at age 16 and genetic differences between students in three school types: state-funded, non-selective schools (‘non-selective’), state-funded, selective schools (‘grammar’) and private schools, which are selective (‘private’). We created a genome-wide polygenic score (GPS) derived from a genome-wide association study of years of education (EduYears). We found substantial mean genetic differences between students of different school types: students in non-selective schools had lower EduYears GPS compared to those in grammar (d = 0.41) and private schools (d = 0.37). Three times as many students in the top EduYears GPS decile went to a selective school compared to the bottom decile. These results were mirrored in the exam differences between school types. However, once we controlled for factors involved in pupil selection, there were no significant genetic differences between school types, and the variance in exam scores at age 16 explained by school type dropped from 7% to <1%. These results show that genetic and exam differences between school types are primarily due to the heritable characteristics involved in pupil admission

Are genetic risk factors for psychosis also associated with dimension-specific psychotic experiences in adolescence?

Psychosis has been hypothesised to be a continuously distributed quantitative phenotype and disorders such as schizophrenia and bipolar disorder represent its extreme manifestations. Evidence suggests that common genetic variants play an important role in liability to both schizophrenia and bipolar disorder. Here we tested the hypothesis that these common variants would also influence psychotic experiences measured dimensionally in adolescents in the general population. Our aim was to test whether schizophrenia and bipolar disorder polygenic risk scores (PRS), as well as specific single nucleotide polymorphisms (SNPs) previously identified as risk variants for schizophrenia, were associated with adolescent dimension-specific psychotic experiences. Self-reported Paranoia, Hallucinations, Cognitive Disorganisation, Grandiosity, Anhedonia, and Parent-rated Negative Symptoms, as measured by the Specific Psychotic Experiences Questionnaire (SPEQ), were assessed in a community sample of 2,152 16-year-olds. Polygenic risk scores were calculated using estimates of the log of odds ratios from the Psychiatric Genomics Consortium GWAS stage-1 mega-analysis of schizophrenia and bipolar disorder. The polygenic risk analyses yielded no significant associations between schizophrenia and bipolar disorder PRS and the SPEQ measures. The analyses on the 28 individual SNPs previously associated with schizophrenia found that two SNPs in TCF4 returned a significant association with the SPEQ Paranoia dimension, rs17512836 (p-value=2.57x10-4) and rs9960767 (p-value=6.23x10-4). Replication in an independent sample of 16-year-olds (N=3,427) assessed using the Psychotic-Like Symptoms Questionnaire (PLIKS-Q), a composite measure of multiple positive psychotic experiences, failed to yield significant results. Future research with PRS derived from larger samples, as well as larger adolescent validation samples, would improve the predictive power to test these hypotheses further. The challenges of relating adult clinical diagnostic constructs such as schizophrenia to adolescent psychotic experiences at a genetic level are discussed

Molecular genetic contributions to socioeconomic status and intelligence

Education, socioeconomic status, and intelligence are commonly used as predictors of health outcomes, social environment, and mortality. Education and socioeconomic status are typically viewed as environmental variables although both correlate with intelligence, which has a substantial genetic basis. Using data from 6815 unrelated subjects from the Generation Scotland study, we examined the genetic contributions to these variables and their genetic correlations. Subjects underwent genome-wide testing for common single nucleotide polymorphisms (SNPs). DNA-derived heritability estimates and genetic correlations were calculated using the ‘Genome-wide Complex Trait Analyses’ (GCTA) procedures. 21% of the variation in education, 18% of the variation in socioeconomic status, and 29% of the variation in general cognitive ability was explained by variation in common SNPs (SEs ~ 5%). The SNP-based genetic correlations of education and socioeconomic status with general intelligence were 0.95 (SE 0.13) and 0.26 (0.16), respectively. There are genetic contributions to intelligence and education with near-complete overlap between common additive SNP effects on these traits (genetic correlation ~ 1). Genetic influences on socioeconomic status are also associated with the genetic foundations of intelligence. The results are also compatible with substantial environmental contributions to socioeconomic status

The correlation between reading and mathematics ability at age twelve has a substantial genetic component

Dissecting how genetic and environmental influences impact on learning is helpful for maximizing numeracy and literacy. Here we show, using twin and genome-wide analysis, that there is a substantial genetic component to children’s ability in reading and mathematics, and estimate that around one half of the observed correlation in these traits is due to shared genetic effects (so-called Generalist Genes). Thus, our results highlight the potential role of the learning environment in contributing to differences in a child’s cognitive abilities at age twelve

Genetics of callous-unemotional behavior in children

Callous-unemotional behavior (CU) is currently under consideration as a subtyping index for conduct disorder diagnosis. Twin studies routinely estimate the heritability of CU as greater than 50%. It is now possible to estimate genetic influence using DNA alone from samples of unrelated individuals, not relying on the assumptions of the twin method. Here we use this new DNA method (implemented in a software package called Genome-wide Complex Trait Analysis, GCTA) for the first time to estimate genetic influence on CU. We also report the first genome-wide association (GWA) study of CU as a quantitative trait. We compare these DNA results to those from twin analyses using the same measure and the same community sample of 2,930 children rated by their teachers at ages 7, 9 and 12. GCTA estimates of heritability were near zero, even though twin analysis of CU in this sample confirmed the high heritability of CU reported in the literature, and even though GCTA estimates of heritability were substantial for cognitive and anthropological traits in this sample. No significant associations were found in GWA analysis, which, like GCTA, only detects additive effects of common DNA variants. The phrase ‘missing heritability’ was coined to refer to the gap between variance associated with DNA variants identified in GWA studies versus twin study heritability. However, GCTA heritability, not twin study heritability, is the ceiling for GWA studies because both GCTA and GWA are limited to the overall additive effects of common DNA variants, whereas twin studies are not. This GCTA ceiling is very low for CU in our study, despite its high twin study heritability estimate. The gap between GCTA and twin study heritabilities will make it challenging to identify genes responsible for the heritability of CU