Common aetiology for diverse language skills in 41/2-year-old twins

Multivariate genetic analysis was used to examine the genetic and environmental aetiology of the interrelationships of diverse linguistic skills. This study used data from a large sample of 4 1/2 year-old twins who were tested on measures assessing articulation, phonology, grammar, vocabulary, and verbal memory. Phenotypic analysis suggested two latent factors: articulation (2 measures) and general language (the remaining 7), and a genetic model incorporating these factors provided a good fit to the data. Almost all genetic and shared environmental influences on the 9 measures acted through the two latent factors. There was also substantial aetiological overlap between the two latent factors, with a genetic correlation of 0·64 and shared environment correlation of 1·00. We conclude that to a large extent, the same genetic and environmental factors underlie the development of individual differences in a wide range of linguistic skills

Mathematics is differentially related to reading comprehension and word decoding: Evidence from a genetically-sensitive design.

Although evidence suggests that individual differences in reading and mathematics skills are correlated, this relationship has typically only been studied in relation to word decoding or global measures of reading. It is unclear whether mathematics is differentially related to word decoding and reading comprehension. The current study examined these relationships at both a phenotypic and etiological level in a population-based cohort of 5162 twin pairs at age 12. Multivariate genetic analyses of latent phenotypic factors of mathematics, word decoding and reading comprehension revealed substantial genetic and shared environmental correlations among all three domains. However, the phenotypic and genetic correlations between mathematics and reading comprehension were significantly greater than between mathematics and word decoding. Independent of mathematics, there was also evidence for genetic and nonshared environmental links between word decoding and reading comprehension. These findings indicate that word decoding and reading comprehension have partly distinct relationships with mathematics in the middle school years

Discontinuation of enzyme replacement therapy in adults with Pompe disease: Evaluating the European POmpe Consortium stop criteria

Enzyme replacement therapy for Pompe disease received market authorization in 2006. To implement this costly treatment in the Netherlands in the most sensible way, a multidisciplinary expert committee was installed. We evaluated decision making in adult patients in relation to the European POmpe Consortium stop criteria. Of 125 adult Pompe patients, 111 started treatment; subsequently treatment stopped in 24 patients (21%). In 10 patients, treatment was discontinued for medical or personal reasons, as defined in the six stop criteria (median treatment duration: 2.1 years, range: 0.3–14.6 years). Three of these patients continued follow-up (follow-up: 1.3–8.0 years), these patients did not display a more rapid decline after discontinuation. In 14 of 24 patients, therapy ended at time of death. In 10 patients death was related to Pompe disease (median treatment duration: 7.2 years, range: 0.4–10.3 years). All 10 patients were severely affected at start of treatment, treatment had elicited positive effects in eight. The European POmpe Consortium guidelines worked well in decision making on stopping treatment. However, (re)evaluation of the rationale for continuation of treatment in advanced disease stage is not addressed. We suggest to add this to the treatment evaluation and to handle treatment decisions in a multidisciplinary expert team

Lateral Trunk Motion and Knee Pain in Osteoarthritis of the Knee: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Patients with osteoarthritis of the knee may change their gait in an attempt to reduce loading of the affected knee, thereby reducing pain. Especially changes in lateral trunk motion may be potentially effective, since these will affect the position of the centre of mass relative to the knee, enabling minimization of the load on the knee and thereby knee pain. The aim of the study was to test the hypothesis that a higher level of knee pain is associated with higher lateral trunk motion in patients with knee OA.</p> <p>Methods</p> <p>Fifty-two patients with OA of the knee were tested. Lateral trunk motion was measured during the stance phase of walking with an optoelectronic motion analysis system and a force plate. Knee pain was measured with the VAS and the WOMAC pain questionnaire. Regression analyses were performed to assess the relationship between lateral trunk motion and knee pain.</p> <p>Results</p> <p>It was shown that in bivariate analyses knee pain was not associated with lateral trunk motion. In regression analyses, pain was associated with more lateral trunk motion. In addition, more lateral trunk motion was associated with younger age, being female, higher self-reported knee stiffness and higher maximum walking speed.</p> <p>Conclusion</p> <p>Pain is associated with lateral trunk motion. This association is weak and is influenced by age, gender, self-reported stiffness and maximum walking speed.</p

Light transmittance in human atrial tissue and transthoracic illumination in rats support translatability of optogenetic cardioversion of atrial fibrillation

Background: Optogenetics could offer a solution to the current lack of an ambulatory method for the rapid automated cardioversion of atrial fibrillation (AF), but key translational aspects remain to be studied. Objective: To investigate whether optogenetic cardioversion of AF is effective in the aged heart and whether sufficient light penetrates the human atrial wall. Methods: Atria of adult and aged rats were optogenetically modified to express light-gated ion channels (i.e., red-activatable channelrhodopsin), followed by AF induction and atrial illumination to determine the effectivity of optogenetic cardioversion. The irradiance level was determined by light transmittance measurements on human atrial tissue. Results: AF could be effectively terminated in the remodeled atria of aged rats (97%, n = 6). Subsequently, ex vivo experiments using human atrial auricles demonstrated that 565-nm light pulses at an intensity of 25 mW/mm(2) achieved the complete penetration of the atrial wall. Applying such irradiation onto the chest of adult rats resulted in transthoracic atrial illumination as evidenced by the optogenetic cardioversion of AF (90%, n = 4). Conclusion: Transthoracic optogenetic cardioversion of AF is effective in the aged rat heart using irradiation levels compatible with human atrial transmural light penetration.Thoracic Surger

A Latent Variable Partial Least Squares Path Modeling Approach to Regional Association and Polygenic Effect with Applications to a Human Obesity Study

Genetic association studies are now routinely used to identify single nucleotide polymorphisms (SNPs) linked with human diseases or traits through single SNP-single trait tests. Here we introduced partial least squares path modeling (PLSPM) for association between single or multiple SNPs and a latent trait that can involve single or multiple correlated measurement(s). Furthermore, the framework naturally provides estimators of polygenic effect by appropriately weighting trait-attributing alleles. We conducted computer simulations to assess the performance via multiple SNPs and human obesity-related traits as measured by body mass index (BMI), waist and hip circumferences. Our results showed that the associate statistics had type I error rates close to nominal level and were powerful for a range of effect and sample sizes. When applied to 12 candidate regions in data (N = 2,417) from the European Prospective Investigation of Cancer (EPIC)-Norfolk study, a region in FTO was found to have stronger association (rs7204609∼rs9939881 at the first intron P = 4.29×10−7) than single SNP analysis (all with P>10−4) and a latent quantitative phenotype was obtained using a subset sample of EPIC-Norfolk (N = 12,559). We believe our method is appropriate for assessment of regional association and polygenic effect on a single or multiple traits

The Genetic Association Between ADHD Symptoms and Reading Difficulties: The Role of Inattentiveness and IQ

Previous studies have documented the primarily genetic aetiology for the stronger phenotypic covariance between reading disability and ADHD inattention symptoms, compared to hyperactivity-impulsivity symptoms. In this study, we examined to what extent this covariation could be attributed to “generalist genes” shared with general cognitive ability or to “specialist” genes which may specifically underlie processes linking inattention symptoms and reading difficulties. We used multivariate structural equation modeling on IQ, parent and teacher ADHD ratings and parent ratings on reading difficulties from a general population sample of 1312 twins aged 7.9–10.9 years. The covariance between reading difficulties and ADHD inattention symptoms was largely driven by genetic (45%) and child-specific environment (21%) factors not shared with IQ and hyperactivity-impulsivity; only 11% of the covariance was due to genetic effects common with IQ. Aetiological influences shared among all phenotypes explained 47% of the variance in reading difficulties. The current study, using a general population sample, extends previous findings by showing, first, that the shared genetic variability between reading difficulties and ADHD inattention symptoms is largely independent from genes contributing to general cognitive ability and, second, that child-specific environment factors, independent from IQ, also contribute to the covariation between reading difficulties and inattention symptoms

Common variation near ROBO2 is associated with expressive vocabulary in infancy

Twin studies suggest that expressive vocabulary at ~24 months is modestly heritable. However, the genes influencing this early linguistic phenotype are unknown. Here we conduct a genome-wide screen and follow-up study of expressive vocabulary in toddlers of European descent from up to four studies of the EArly Genetics and Lifecourse Epidemiology consortium, analysing an early (15–18 months, ‘one-word stage’, NTotal=8,889) and a later (24–30 months, ‘two-word stage’, NTotal=10,819) phase of language acquisition. For the early phase, one single-nucleotide polymorphism (rs7642482) at 3p12.3 near ​ROBO2, encoding a conserved axon-binding receptor, reaches the genome-wide significance level (P=1.3 × 10−8) in the combined sample. This association links language-related common genetic variation in the general population to a potential autism susceptibility locus and a linkage region for dyslexia, speech-sound disorder and reading. The contribution of common genetic influences is, although modest, supported by genome-wide complex trait analysis (meta-GCTA h215–18-months=0.13, meta-GCTA h224–30-months=0.14) and in concordance with additional twin analysis (5,733 pairs of European descent, h224-months=0.20)

Gene-Environment Interaction in the Etiology of Mathematical Ability Using SNP Sets

Mathematics ability and disability is as heritable as other cognitive abilities and disabilities, however its genetic etiology has received relatively little attention. In our recent genome-wide association study of mathematical ability in 10-year-old children, 10 SNP associations were nominated from scans of pooled DNA and validated in an individually genotyped sample. In this paper, we use a ‘SNP set’ composite of these 10 SNPs to investigate gene-environment (GE) interaction, examining whether the association between the 10-SNP set and mathematical ability differs as a function of ten environmental measures in the home and school in a sample of 1888 children with complete data. We found two significant GE interactions for environmental measures in the home and the school both in the direction of the diathesis-stress type of GE interaction: The 10-SNP set was more strongly associated with mathematical ability in chaotic homes and when parents are negative