Adiposity among children in Norway by urbanity and maternal education: a nationally representative study

BACKGROUND: International research has demonstrated that rural residency is a risk factor for childhood adiposity. The main aim of this study was to investigate the urban-rural gradient in overweight and obesity and whether the association differed by maternal education. METHODS: Height, weight and waist circumference (WC) were measured in a nationally representative sample of 3166 Norwegian eight-year-olds in 2010. Anthropometric measures were stratified by area of residence (urbanity) and maternal education. Risk estimates for overweight (including obesity) and waist-to-height ratio ≥0.5 were calculated by log-binomial regression. RESULTS: Mean BMI and WC and risk estimates of overweight (including obesity) and waist-to-height ratio ≥0.5 were associated with both urbanity and maternal education. These associations were robust after mutual adjustment for each other. Furthermore, there was an indication of interaction between urbanity and maternal education, as trends of mean BMI and WC increased from urban to rural residence among children of low-educated mothers (p = 0.01 for both BMI and WC), whereas corresponding trends for children from higher educational background were non-significant (p > 0.30). However, formal tests of the interaction term urbanity by maternal education were non-significant (p-value for interaction was 0.29 for BMI and 0.31 for WC). CONCLUSIONS: In this nationally representative study, children living rurally and children of low-educated mothers had higher mean BMI and waist circumference than children living in more urban areas and children of higher educated mothers

Mutations in HECW2 are associated with intellectual disability and epilepsy

BACKGROUND: De novo mutations are a frequent cause of disorders related to brain development. We report the results of screening patients diagnosed with both epilepsy and intellectual disability (ID) using exome sequencing to identify known and new causative de novo mutations relevant to these conditions. METHODS: Exome sequencing was performed on 39 patient-parent trios to identify de novo mutations. Clinical significance of de novo mutations in genes was determined using the American College of Medical Genetics and Genomics standard guidelines for interpretation of coding variants. Variants in genes of unknown clinical significance were further analysed in the context of previous trio sequencing efforts in neurodevelopmental disorders. RESULTS: In 39 patient-parent trios we identified 29 de novo mutations in coding sequence. Analysis of de novo and inherited variants yielded a molecular diagnosis in 11 families (28.2%). In combination with previously published exome sequencing results in neurodevelopmental disorders, our analysis implicates HECW2 as a novel candidate gene in ID and epilepsy. CONCLUSIONS: Our results support the use of exome sequencing as a diagnostic approach for ID and epilepsy, and confirm previous results regarding the importance of de novo mutations in this patient group. The results also highlight the utility of network analysis and comparison to previous large-scale studies as strategies to prioritise candidate genes for further studies. This study adds knowledge to the increasingly growing list of causative and candidate genes in ID and epilepsy and highlights HECW2 as a new candidate gene for neurodevelopmental disorders

Exome sequencing reveals NAA15 and PUF60 as candidate genes associated with intellectual disability

Intellectual Disability (ID) is a clinically heterogeneous condition that affects 2-3% of population worldwide. In recent years, exome sequencing has been a successful strategy for studies of genetic causes of ID, providing a growing list of both candidate and validated ID genes. In this study, exome sequencing was performed on 28 ID patients in 27 patient-parent trios with the aim to identify de novo variants (DNVs) in known and novel ID associated genes. We report the identification of 25 DNVs out of which five were classified as pathogenic or likely pathogenic. Among these, a two base pair deletion was identified in the PUF60 gene, which is one of three genes in the critical region of the 8q24.3 microdeletion syndrome (Verheij syndrome). Our result adds to the growing evidence that PUF60 is responsible for the majority of the symptoms reported for carriers of a microdeletion across this region. We also report variants in several genes previously not associated with ID, including a de novo missense variant in NAA15. We highlight NAA15 as a novel candidate ID gene based on the vital role of NAA15 in the generation and differentiation of neurons in neonatal brain, the fact that the gene is highly intolerant to loss of function and coding variation, and previously reported DNVs in neurodevelopmental disorders