Where you live matters: visualizing environmental effects on reading attainment.

BACKGROUND: The way in which socioeconomic status (SES) moderates the etiology of reading attainment has been explored many times, with past work often finding that genetic influences are suppressed under conditions of socioeconomic deprivation and more fully realized under conditions of socioeconomic advantage: a gene-SES interaction. Additionally, past work has pointed toward the presence of gene-location interactions, with the relative influence of genes and environment varying across geographic regions of the same country/state. METHOD: This study investigates the extent to which SES and geographical location interact to moderate the genetic and environmental components of reading attainment. Utilizing data from 2,135 twin pairs in Florida (mean age 13.82 years, range 10.71-17.77), the study operationalized reading attainment as reading comprehension scores from a statewide test and SES as household income. We applied a spatial twin analysis procedure to investigate how twin genetic and environmental estimates vary by geographic location. We then expanded this analysis to explore how the moderating role of SES on said genetic and environmental influences also varied by geographic location. RESULTS: A gene-SES interaction was found, with heritability of reading being suppressed in lower- (23%) versus higher-SES homes (78%). The magnitude of the moderating parameters were not consistent by location, however, and ranged from -0.10 to 0.10 for the moderating effect on genetic influences, and from -0.30 to 0.05 for the moderating effect on environmental influences. For smaller areas and those with less socioeconomic variability, the magnitude of the genetic moderating parameter was high, giving rise to more fully realized genetic influences on reading there. CONCLUSIONS: SES significantly influences reading variability. However, a child's home location matters in both the overall etiology and how strongly SES moderates said etiologies. These results point toward the presence of multiple significant environmental factors that simultaneously, and inseparably, influence the underlying etiology of reading attainment.

Assessing the effectiveness of online emotion recognition training in healthy volunteers.

Facial emotion recognition (ER) difficulties are associated with mental health and neurodevelopmental conditions, including autism and poorer social functioning. ER interventions may therefore have clinical potential. We investigated the efficacy of ER training (ERT). We conducted three online studies with healthy volunteers completing one ERT session. Studies 1 and 2 included active and control/sham training groups and tested the efficacy of (i) four-emotion ERT (angry, happy, sad and scared) (n = 101), and (ii) six-emotion ERT (adding disgusted and surprised) (n = 109). Study 3 tested generalizability of ERT to non-trained stimuli with groups trained and tested on the same stimuli, or different stimuli (n = 120). Training effects on total correct hits were estimated using linear mixed effects models. We did not observe clear evidence of improvement in study 1 but note the effect was in the direction of improvement (b = 0.02, 95% confidence interval (CI) = -0.02 to 0.07). Study 2 indicated greater total hits following training (b = 0.07, 95% CI = 0.03-0.12). Study 3 demonstrated similar improvement across groups (b = -0.01, 95% CI = -0.05 to 0.02). Our results indicate improved ER (as measured by our task), which generalizes to different facial stimulus sets. Future studies should further explore generalizability, longer-term effects and ERT in populations with known ER difficulties.

The absence of association between anorexia nervosa and smoking: converging evidence across two studies.

Previous studies have found increased smoking prevalence amongst adults with anorexia nervosa (AN) compared to the general population. The current investigation explored bidirectional associations between AN and smoking behaviour (initiation and heaviness), to address questions surrounding causation. In Study One, logistic regression models with variance robust standard errors assessed longitudinal associations between AN and smoking, using data from adolescent participants of the Avon Longitudinal Study of Parents and Children (N = 5100). In Study Two, two-sample Mendelian randomisation (MR) tested possible causal effects using summary statistics from publicly available genome-wide association studies (GWAS). Study One provided no clear evidence for a predictive effect of AN on subsequent smoking behaviour, or for smoking heaviness/initiation predicting later AN. MR findings did not support causal effects between AN and smoking behaviour, in either direction. Findings do not support predictive or causal effects between AN and smoking behaviour. Previously reported associations may have been vulnerable to confounding, highlighting the possibility of smoking and AN sharing causal risk factors.

Is there a causal relationship between executive function and liability to mental health and substance use? A Mendelian randomization approach.

Poorer performance in tasks testing executive function (EF) is associated with a range of psychopathologies such as schizophrenia, major depressive disorder (MDD) and anxiety, as well as smoking and alcohol consumption. We used two-sample bidirectional Mendelian randomization to examine whether these may reflect causal relationships and the direction of causation. We used genome-wide association study summary data (N = 17 310 to 848 460) for a common EF factor score (cEF), schizophrenia, MDD, anxiety, smoking initiation, alcohol consumption, alcohol dependence and cannabis use disorder (CUD). We found evidence of increased cEF on reduced schizophrenia liability (OR = 0.10; CI: 0.05 to 0.19; p-value = 3.43 × 10-12), MDD liability (OR = 0.52; CI: 0.38 to 0.72; p-value = 5.23 × 10-05), drinks per week (ß = -0.06; CI: -0.10 to -0.02; p-value = 0.003) and CUD liability (OR = 0.27; CI: 0.12 to 0.61; p-value = 1.58 × 10-03). We also found evidence of increased schizophrenia liability (ß = -0.04; CI: -0.04 to -0.03; p-value = 3.25 × 10-27) and smoking initiation on decreased cEF (ß = -0.06; CI: -0.09 to -0.03; p-value = 6.11 × 10-05). Our results indicate potential causal relationships between cEF and mental health and substance use. Further studies are required to improve our understanding of the underlying mechanisms of these effects, but our results suggest that EF may be a promising intervention target for mental health and substance use.

Using Mendelian randomization to explore the gateway hypothesis: possible causal effects of smoking initiation and alcohol consumption on substance use outcomes.

BACKGROUND AND AIMS: Initial use of drugs such as tobacco and alcohol may lead to subsequent more problematic drug use-the 'gateway' hypothesis. However, observed associations may be due to a shared underlying risk factor, such as trait impulsivity. We used bidirectional Mendelian randomization (MR) to test the gateway hypothesis. DESIGN: Our main method was inverse-variance weighted (IVW) MR, with other methods included as sensitivity analyses (where consistent results across methods would raise confidence in our primary results). MR is a genetic instrumental variable approach used to support stronger causal inference in observational studies. SETTING AND PARTICIPANTS: Genome-wide association summary data among European ancestry individuals for smoking initiation, alcoholic drinks per week, cannabis use and dependence, cocaine and opioid dependence (n = 1749-1 232 091). MEASUREMENTS: Genetic variants for exposure. FINDINGS: We found evidence of causal effects from smoking initiation to increased drinks per week [(IVW): ß = 0.06; 95% confidence interval (CI) = 0.03-0.09; P = 9.44 × 10-06 ], cannabis use [IVW: odds ratio (OR) = 1.34; 95% CI = 1.24-1.44; P = 1.95 × 10-14 ] and cannabis dependence (IVW: OR = 1.68; 95% CI = 1.12-2.51; P = 0.01). We also found evidence of an effect of cannabis use on the increased likelihood of smoking initiation (IVW: OR = 1.39; 95% CI = 1.08-1.80; P = 0.01). We did not find evidence of an effect of drinks per week on other substance use outcomes, except weak evidence of an effect on cannabis use (IVW: OR = 0.55; 95% CI = 0.16-1.93; P-value = 0.35). We found weak evidence of an effect of opioid dependence on increased drinks per week (IVW: ß = 0.002; 95% CI = 0.0005-0.003; P = 8.61 × 10-03 ). CONCLUSIONS: Bidirectional Mendelian randomization testing of the gateway hypothesis reveals that smoking initiation may lead to increased alcohol consumption, cannabis use and cannabis dependence. Cannabis use may also lead to smoking initiation and opioid dependence to alcohol consumption. However, given that tobacco and alcohol use typically begin before other drug use, these results may reflect a shared risk factor or a bidirectional effect for cannabis use and opioid dependence.

Examining the bidirectional association between emotion recognition and social autistic traits using observational and genetic analyses.

BACKGROUND: There is mixed evidence for an association between autism spectrum disorder (ASD) and emotion recognition deficits. We sought to assess the bidirectionality of this association using phenotypic and genetic data in a large community sample. METHODS: Analyses were conducted in three stages. First, we examined the bidirectional association between social autistic traits at age 8 years and emotion recognition task (ERT) responses at age 24 years (Study 1; N = 3,562); and between Diagnostic Analysis of Non-Verbal Accuracy (DANVA) emotion recognition responses at age 8 years and social autistic traits at age 10 years (Study 2; N = 9,071). Next, we used genetic analyses (Study 3) to examine the association between polygenic risk scores for ASD and outcomes for the ERT and DANVA. The genetic correlation between ASD and ERT responses at age 24 was also estimated. Analyses were conducted in the Avon Longitudinal Study of Parents and Children. RESULTS: Social autistic traits at age 8 years were negatively associated with later total correct responses on ERT in Study 1 (b = -0.18; 95% CI: -0.27 to -0.09). We also found evidence of an association in Study 2 (b = -0.04; 95% CI: -0.05 to -0.03). We found the opposite association, that is positive, between the ASD polygenic risk score and ERT (b = 0.40; 95% CI: 0.10 to 0.70); however, this association varied across different p-value thresholds and would not survive multiple testing, so should be interpreted with caution. We did not find evidence of a genetic correlation between ASD and ERT. CONCLUSION: We found an observational association between poorer emotion recognition and increased social autistic traits. Our genetic analyses may suggest a shared genetic aetiology between these or a potential causal pathway; however, future research would benefit from using better powered GWAS to examine this further. Our results may inform interventions targeting emotion recognition.

Mapping the genetic and environmental aetiology of autistic traits in Sweden and the United Kingdom.

Background: Autistic traits are influenced by both genetic and environmental factors, and are known to vary geographically in prevalence. But to what extent does their aetiology also vary from place to place? Methods: We applied a novel spatial approach to data on autistic traits from two large twin studies, the Child and Adolescent Twin Study in Sweden (CATSS; N = 16,677, including 8307 twin pairs) and the Twins Early Development Study in the UK (TEDS; N = 11,594, including 5796 twin pairs), to explore how the influence of nature and nurture on autistic traits varies from place to place. Results: We present maps of gene- and environment- by geography interactions in Sweden and the United Kingdom (UK), showing geographical variation in both genetic and environmental influences across the two countries. In Sweden genetic influences appear higher in the far south and in a band running across the centre of the country. Environmental influences appear greatest in the south and north, with reduced environmental influence across the central band. In the UK genetic influences appear greater in the south, particularly in more central southern areas and the southeast, the Midlands and the north of England. Environmental influences appear greatest in the south and east of the UK, with less influence in the north and the west. Conclusions: We hope this systematic approach to identifying aetiological interactions will inspire research to examine a wider range of previously unknown environmental influences on the aetiology of autistic traits. By doing so, we will gain greater understanding of how these environments draw out or mask genetic predisposition and interact with other environmental influences in the development of autistic traits.

The association of DNA methylation with body mass index: distinguishing between predictors and biomarkers.

BACKGROUND: DNA methylation is associated with body mass index (BMI), but it is not clear if methylation scores are biomarkers for extant BMI or predictive of future BMI. Here, we explore the causal nature and predictive utility of DNA methylation measured in peripheral blood with BMI and cardiometabolic traits. METHODS: Analyses were conducted across the life course using the ARIES cohort of mothers (n = 792) and children (n = 906), for whom DNA methylation and genetic profiles and BMI at multiple time points (3 in children at birth, in childhood and in adolescence; 2 in mothers during pregnancy and in middle age) were available. Genetic and DNA methylation scores for BMI were derived using published associations between BMI and DNA methylation and genotype. Causal relationships between methylation and BMI were assessed using Mendelian randomisation and cross-lagged models. RESULTS: The DNA methylation scores in adult women explained 10% of extant BMI variance. However, less extant variance was explained by scores generated in the same women during pregnancy (2% BMI variance) and in older children (15-17 years; 3% BMI variance). Similarly, little extant variance was explained in younger children (at birth and at 7 years; 1% and 2%, respectively). These associations remained following adjustment for smoking exposure and education levels. The DNA methylation score was found to be a poor predictor of future BMI using linear and cross-lagged models, suggesting that DNA methylation variation does not cause later variation in BMI. However, there was some evidence to suggest that BMI is predictive of later DNA methylation. Mendelian randomisation analyses also support this direction of effect, although evidence is weak. Finally, we find that DNA methylation scores for BMI are associated with extant cardiometabolic traits independently of BMI and genetic score. CONCLUSION: The age-specific nature of DNA methylation associations with BMI, lack of causal relationship and limited predictive ability of future BMI indicate that DNA methylation is likely influenced by BMI and might more accurately be considered a biomarker of BMI and related outcomes rather than a predictor. Future epigenome-wide association studies may benefit from further examining associations between early DNA methylation and later health outcomes.

Schizophrenia liability shares common molecular genetic risk factors with sleep duration and nightmares in childhood.

Background: Sleep abnormalities are common in schizophrenia, often appearing before psychosis onset; however, the mechanisms behind this are uncertain. We investigated whether genetic risk for schizophrenia is associated with sleep phenotypes. Methods: We used data from 6,058 children and 2,302 mothers from the Avon Longitudinal Study of Parents and Children (ALSPAC). We examined associations between a polygenic risk score for schizophrenia and sleep duration in both children and mothers, and nightmares in children, along with genetic covariances between these traits. Results: Polygenic risk for schizophrenia was associated with increased risk of nightmares (OR=1.07, 95% CI: 1.01, 1.14, p=0.02) in children, and also with less sleep (ß=-44.52, 95% CI: -88.98, -0.07; p=0.05). We observed a similar relationship with sleep duration in mothers, although evidence was much weaker (p=0.38). Finally, we found evidence of genetic covariance between schizophrenia risk and reduced sleep duration in children and mothers, and between schizophrenia risk and nightmares in children. Conclusions: These molecular genetic results support recent findings from twin analysis that show genetic overlap between sleep disturbances and psychotic-like experiences. They also show, to our knowledge for the first time, a genetic correlation between schizophrenia liability and risk of nightmares in childhood.

Plasma glutathione suggests oxidative stress is equally present in early- and late-onset bipolar disorder.

OBJECTIVES: We previously demonstrated oxidative stress in bipolar patients and a relationship between the age of illness onset and total glutathione, a principal antioxidant. In this study, we sought to replicate these findings in a new cohort of patients. METHODS: We recruited bipolar patients from Warneford Hospital, Oxford, UK, of similar age and grouped them according to age of onset of illness. The early-onset group comprised patients with onset at <23 years, and the late group comprised patients with onset at >30 years. A third group, comprising age-matched healthy volunteers, was also included. Reduced and oxidized glutathione, cysteine, and cystine were determined in plasma, using high-performance liquid chromatography. Mitochondrial DNA copy number, measured in whole blood, was also compared between patients and healthy controls. RESULTS: Significant increases in oxidative stress were observed in the patient groups, compared with the control group; however, no differences in glutathione-related oxidative stress measures were detected between the early- and late-onset bipolar patient groups. No differences were observed in the amount of mitochondrial DNA, and there was no correlation with mood state. CONCLUSION: Using a more accurate method to quantify oxidative stress than in our previous study, we show that oxidative stress is a consistent feature of bipolar disorder. Although we did not reproduce our finding correlating age of onset of illness to oxidative stress, we have shown, once again, that oxidative stress is a consistent feature of bipolar disorder.

Use of 2-octyl cyanoacrylate for wound closure in a modified Roberts-Bistner procedure for eyelid agenesis in five cats (nine eyes).

CASE DESCRIPTION 5 cats (9 eyes) were evaluated for surgical correction of bilateral eyelid agenesis. CLINICAL FINDINGS All eyes lacked > 25% of the temporal upper eyelid, and all cats had clinical signs attributable to chronic ocular exposure. Abnormalities were limited to the ocular surface in the 4 female cats, whereas the sole male cat had additional abnormalities consistent with anterior segment dysgenesis. TREATMENT AND OUTCOME A modified Roberts-Bistner procedure involving 2-octyl cyanoacrylate (2OCA) was performed on 9 eyes; 1 eye was enucleated. Surgical wounds in the initial 3 eyes were closed with 2OCA plus sutures, and flaps were lined with conjunctiva. The technique was optimized for remaining eyes by use of a single suture for flap apposition, no conjunctival lining of flaps, and 2OCA alone for wound closure. Median duration of surgery was 35 minutes/eye for the initial 3 eyes versus 16 minutes/eye for the subsequent 6 eyes treated with the optimized procedure. After surgery, all cats had complete palpebral reflexes and resolution of clinical signs of ocular irritation. Minor complications in the early postoperative period included eyelid swelling (n = 9), poor cosmesis (7), and persistent epiphora (3). By the second recheck examination, swelling had resolved and cosmesis was considered excellent. Two eyes with epiphora had been treated with the initial modified procedure and required cryoepilation for resolution of epiphora. CLINICAL RELEVANCE The modified Roberts-Bistner procedure for eyelid agenesis involving 2OCA for wound closure provided functional, cosmetic eyelids that improved comfort and provided protection of the ocular surface in affected cats.

Assessing the causal role of adiposity on disordered eating in childhood, adolescence, and adulthood: a Mendelian randomization analysis.

Background: Observational studies have shown that higher body mass index (BMI) is associated with increased risk of developing disordered eating patterns. However, the causal direction of this relation remains ambiguous.Objective: We used Mendelian randomization (MR) to infer the direction of causality between BMI and disordered eating in childhood, adolescence, and adulthood.Design: MR analyses were conducted with a genetic score as an instrumental variable for BMI to assess the causal effect of BMI at age 7 y on disordered eating patterns at age 13 y with the use of data from the Avon Longitudinal Study of Parents and Children (ALSPAC) (n = 4473). To examine causality in the reverse direction, MR analyses were used to estimate the effect of the same disordered eating patterns at age 13 y on BMI at age 17 y via a split-sample approach in the ALSPAC. We also investigated the causal direction of the association between BMI and eating disorders (EDs) in adults via a two-sample MR approach and publically available genome-wide association study data.Results: MR results indicated that higher BMI at age 7 y likely causes higher levels of binge eating and overeating, weight and shape concerns, and weight-control behavior patterns in both males and females and food restriction in males at age 13 y. Furthermore, results suggested that higher levels of binge eating and overeating in males at age 13 y likely cause higher BMI at age 17 y. We showed no evidence of causality between BMI and EDs in adulthood in either direction.Conclusions: This study provides evidence to suggest a causal effect of higher BMI in childhood and increased risk of disordered eating at age 13 y. Furthermore, higher levels of binge eating and overeating may cause higher BMI in later life. These results encourage an exploration of the ways to break the causal chain between these complex phenotypes, which could inform and prevent disordered eating problems in adolescence.

Tarantula Hair Keratoconjunctivitis with Concurrent Fungal Infection in a Rat Terrier.

A 9 yr old rat terrier presented with corneal ulceration and conjunctivitis that developed acutely after digging among dry leaves in wooded northern Arizona. Ophthalmic examination revealed multiple linear foreign bodies throughout the adnexal tissue and cornea of the left eye. Manual removal of material was unsuccessful. The palpebral conjunctiva required excision with tenotomy scissors to remove structures and allow corneal healing. Microscopic examination revealed structures believed to be setae from a Theraphosidae tarantula. This was confirmed morphologically by an entomologist and by comparison with hairs from a captive spider of the suspected species. The excised tissue also contained fruiting bodies, hyphae, and microconidia consistent with Aspergillus spp. The captive spider hairs also cultured positive for Aspergillus, suggesting a relationship between this fungus and tarantulas in captivity and in their native habitat. This is the first report in the veterinary literature to confirm tarantula hair as the causative agent in keratoconjunctivitis and corneal ulceration, adding it to the list of differential diagnoses for ocular foreign body. This is also the first report to suggest a relationship between Aspergillus and tarantulas of the Theraphosidae family, which should be considered in the diagnostics and treatment of patients with suspected tarantula hair keratoconjunctivitis.

Clinical comparison of the Welch Allyn SureSight™ handheld autorefractor vs. streak retinoscopy in dogs.

OBJECTIVE: To compare the Welch Allyn SureSight™ wavefront autorefractor with retinoscopy in normal dogs. ANIMALS STUDIED: Fifty privately owned dogs (100 eyes) of 20 breeds, free of ocular disease. Mean ± SD age: 5.7 ± 3.25 years (range: 6 months-13 years). PROCEDURES: The refractive error was determined in each eye by two experienced retinoscopists using streak retinoscopy as well as by an autorefractor operated by two different examiners. Measurements were performed before and approximately 30-45 min after cycloplegia was induced by cyclopentolate 0.5% and tropicamide 0.5% ophthalmic solutions. RESULTS: Mean ± SD noncyclopleged retinoscopy net sphere was -0.55 ± 1.14 (range: -3.75 to 3.5) diopters (D). Mean cyclopleged retinoscopy net sphere was -0.52 ± 1.18 (range: -4.25 to 2) D. Mean ± SD noncyclopleged autorefractor spherical equivalent (SE) was -0.42 ± 1.13 D (range: -3.36 to 2.73) D. Mean cyclopleged autorefractor SE was 0.10 ± 1.47 (range: -5.62 to 3.19) D. Noncyclopleged autorefraction results were not significantly different from streak retinoscopy (whether noncyclopleged or cyclopleged, P = 0.80 and P = 0.26, respectively). Cyclopleged autorefraction results were significantly different from noncyclopleged or cyclopleged streak retinoscopy (P < 0.0001 in both states). There was no significant difference between noncyclopleged and cyclopleged streak retinoscopy (P = 0.97). CONCLUSIONS: Noncyclopleged autorefraction shows good agreement with streak retinoscopy in dogs and may be a useful clinical technique. Cycloplegia does not significantly affect streak retinoscopy results in dogs.