Genome-wide association study identifies loci associated with liability to alcohol and drug dependence that is associated with variability in reward-related ventral striatum activity in African- and European-Americans.

Genetic influences on alcohol and drug dependence partially overlap, however, specific loci underlying this overlap remain unclear. We conducted a genome-wide association study (GWAS) of a phenotype representing alcohol or illicit drug dependence (ANYDEP) among 7291 European-Americans (EA; 2927 cases) and 3132 African-Americans (AA: 1315 cases) participating in the family-based Collaborative Study on the Genetics of Alcoholism. ANYDEP was heritable (h 2 in EA = 0.60, AA = 0.37). The AA GWAS identified three regions with genome-wide significant (GWS; P < 5E-08) single nucleotide polymorphisms (SNPs) on chromosomes 3 (rs34066662, rs58801820) and 13 (rs75168521, rs78886294), and an insertion-deletion on chromosome 5 (chr5:141988181). No polymorphisms reached GWS in the EA. One GWS region (chromosome 1: rs1890881) emerged from a trans-ancestral meta-analysis (EA + AA) of ANYDEP, and was attributable to alcohol dependence in both samples. Four genes (AA: CRKL, DZIP3, SBK3; EA: P2RX6) and four sets of genes were significantly enriched within biological pathways for hemostasis and signal transduction. GWS signals did not replicate in two independent samples but there was weak evidence for association between rs1890881 and alcohol intake in the UK Biobank. Among 118 AA and 481 EA individuals from the Duke Neurogenetics Study, rs75168521 and rs1890881 genotypes were associated with variability in reward-related ventral striatum activation. This study identified novel loci for substance dependence and provides preliminary evidence that these variants are also associated with individual differences in neural reward reactivity. Gene discovery efforts in non-European samples with distinct patterns of substance use may lead to the identification of novel ancestry-specific genetic markers of risk

Detecting and correcting partial errors: Evidence for efficient control without conscious access

Appropriate reactions to erroneous actions are essential to keeping behavior adaptive. Erring, however, is not an all-or-none process: electromyographic (EMG) recordings of the responding muscles have revealed that covert incorrect response activations (termed "partial errors") occur on a proportion of overtly correct trials. The occurrence of such "partial errors" shows that incorrect response activations could be corrected online, before turning into overt errors. In the present study, we showed that, unlike overt errors, such "partial errors" are poorly consciously detected by participants, who could report only one third of their partial errors. Two parameters of the partial errors were found to predict detection: the surface of the incorrect EMG burst (larger for detected) and the correction time (between the incorrect and correct EMG onsets; longer for detected). These two parameters provided independent information. The correct(ive) responses associated with detected partial errors were larger than the "pure-correct" ones, and this increase was likely a consequence, rather than a cause, of the detection. The respective impacts of the two parameters predicting detection (incorrect surface and correction time), along with the underlying physiological processes subtending partial-error detection, are discussed

Effect of early and current Helicobacter pylori infection on the risk of anaemia in 6.5-year-old Ethiopian children

Background: Epidemiological and clinical studies in high income countries have suggested that Helicobacter pylori (H. pylori) may cause anaemia, but evidence is lacking from low income countries.We examined associations between H. pylori infection in early childhood and anaemia at the age of 6.5 years in an Ethiopian birth cohort. Methods: In 2011/12, 856 children (85.1 % of the 1006 original singletons in a population-based birth cohort) were followed up at age six and half. An interviewer-led questionnaire administered to mothers provided information on demographic and lifestyle variables. Haemoglobin level and red cell indices were examined using an automated haematological analyzer (Cell Dyn 1800, Abbott, USA), and stool samples analyzed for H. pylori antigen. The independent effects of H. pylori infection (measured at age 3.5 and 6.5 years) on anaemia, haemoglobin level, and red cell indices (measured at age 6.5 years) were determined using multiple logistic and linear regression. Results: The prevalence of anemia was 34.8 % (257/739), and the mean (SD) haemoglobin concentration was 11.8 (1.1) gm/dl. Current H. pylori infection at age 6.5 years was positively, though not significantly related to prevalence of anaemia (adjusted OR, 95 % CI, 1.15; 0.69, 1.93, p = 0.59). Any H. pylori infection up to age 6.5 years was significantly associated with an increased risk of anaemia at age 6.5 (adjusted OR, 95 % CI, 1.68; 1.22, 2.32, p = 0.01). A significant reduction in haemoglobin concentration and red cell indices was also observed among children who had any H. pylori infection up to age 6.5 (Hb adjusted β = −0.19, 95 % CI, −0.35 to −0.03, p = 0.01; MCV adjusted β = −2.22, 95 % CI, −3.43 to −1.01, p = 0.01; MCH adjusted β = −0.63, 95 % CI, −1.15 to - 0.12, p = 0.01; and MCHC adjusted β = −0.67, 95 % CI, −1.21 to −0.14, p = 0.01), respectively. Conclusion: This study provides further evidence from a low income country that any H. pylori infection up to age 6.5 is associated with higher prevalence of anaemia, and reduction of haemoglobin level and red cell indices at age 6.5

Proprioceptive loss and the perception, control and learning of arm movements in humans: evidence from sensory neuronopathy

© 2018 The Author(s) It is uncertain how vision and proprioception contribute to adaptation of voluntary arm movements. In normal participants, adaptation to imposed forces is possible with or without vision, suggesting that proprioception is sufficient; in participants with proprioceptive loss (PL), adaptation is possible with visual feedback, suggesting that proprioception is unnecessary. In experiment 1 adaptation to, and retention of, perturbing forces were evaluated in three chronically deafferented participants. They made rapid reaching movements to move a cursor toward a visual target, and a planar robot arm applied orthogonal velocity-dependent forces. Trial-by-trial error correction was observed in all participants. Such adaptation has been characterized with a dual-rate model: a fast process that learns quickly, but retains poorly and a slow process that learns slowly and retains well. Experiment 2 showed that the PL participants had large individual differences in learning and retention rates compared to normal controls. Experiment 3 tested participants’ perception of applied forces. With visual feedback, the PL participants could report the perturbation’s direction as well as controls; without visual feedback, thresholds were elevated. Experiment 4 showed, in healthy participants, that force direction could be estimated from head motion, at levels close to the no-vision threshold for the PL participants. Our results show that proprioceptive loss influences perception, motor control and adaptation but that proprioception from the moving limb is not essential for adaptation to, or detection of, force fields. The differences in learning and retention seen between the three deafferented participants suggest that they achieve these tasks in idiosyncratic ways after proprioceptive loss, possibly integrating visual and vestibular information with individual cognitive strategies

Genome­-wide association study of alcohol consumption and genetic overlap with other health-­related traits in UK Biobank (<i>N </i>=112,117)

Alcohol consumption has been linked to over 200 diseases and is responsible for over 5% of the global disease burden. Well-known genetic variants in alcohol metabolizing genes, for example, ALDH2 and ADH1B, are strongly associated with alcohol consumption but have limited impact in European populations where they are found at low frequency. We performed a genome-wide association study (GWAS) of self-reported alcohol consumption in 112 117 individuals in the UK Biobank (UKB) sample of white British individuals. We report significant genome-wide associations at 14 loci. These include single-nucleotide polymorphisms (SNPs) in alcohol metabolizing genes (ADH1B/ADH1C/ADH5) and two loci in KLB, a gene recently associated with alcohol consumption. We also identify SNPs at novel loci including GCKR, CADM2 and FAM69C. Gene-based analyses found significant associations with genes implicated in the neurobiology of substance use (DRD2, PDE4B). GCTA analyses found a significant SNP-based heritability of self-reported alcohol consumption of 13% (se=0.01). Sex-specific analyses found largely overlapping GWAS loci and the genetic correlation (rG) between male and female alcohol consumption was 0.90 (s.e.=0.09, P-value=7.16 × 10(-23)). Using LD score regression, genetic overlap was found between alcohol consumption and years of schooling (rG=0.18, s.e.=0.03), high-density lipoprotein cholesterol (rG=0.28, s.e.=0.05), smoking (rG=0.40, s.e.=0.06) and various anthropometric traits (for example, overweight, rG=-0.19, s.e.=0.05). This study replicates the association between alcohol consumption and alcohol metabolizing genes and KLB, and identifies novel gene associations that should be the focus of future studies investigating the neurobiology of alcohol consumption

Colorimetric nanofibers as optical sensors

Sensors play a major role in many applications today, ranging from biomedicine to safety equipment, where they detect and warn us about changes in the environment. Nanofibers, characterized by high porosity, flexibility, and a large specific surface area, are the ideal material for ultrasensitive, fastresponding, and user-friendly sensor design. Indeed, a large specific surface area increases the sensitivity and response time of the sensor as the contact area with the analyte is enlarged. Thanks to the flexibility of membranes, nanofibrous sensors cannot only be applied in high-end analyte detection, but also in personal, daily use. Many different nanofibrous sensors have already been designed; albeit, the most straightforward and easiest-to-interpret sensor response is a visual change in color, which is of particular interest in the case of warning signals. Recently, many researchers have focused on the design of so-called colorimetric nanofibers, which typically involve the incorporation of a colorimetric functionality into the nanofibrous matrix. Many different strategies have been used and explored for colorimetric nanofibrous sensor design, which are outlined in this feature article. The many examples and applications demonstrate the value of colorimetric nanofibers for advanced optical sensor design, and could provide directions for future research in this area

Transancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders

Liability to alcohol dependence (AD) is heritable, but little is known about its complex polygenic architecture or its genetic relationship with other disorders. To discover loci associated with AD and characterize the relationship between AD and other psychiatric and behavioral outcomes, we carried out the largest genome-wide association study to date of DSM-IV-diagnosed AD. Genome-wide data on 14,904 individuals with AD and 37,944 controls from 28 case-control and family-based studies were meta-analyzed, stratified by genetic ancestry (European, n = 46,568; African, n = 6,280). Independent, genome-wide significant effects of different ADH1B variants were identified in European (rs1229984; P = 9.8 x 10(-13)) and African ancestries (rs2066702; P = 2.2 x 10(-9)). Significant genetic correlations were observed with 17 phenotypes, including schizophrenia, attention deficit-hyperactivity disorder, depression, and use of cigarettes and cannabis. The genetic underpinnings of AD only partially overlap with those for alcohol consumption, underscoring the genetic distinction between pathological and nonpathological drinking behaviors.Peer reviewe