Rare and low-frequency exonic variants and gene-by-smoking interactions in pulmonary function

Genome-wide association studies have identified numerous common genetic variants associated with spirometric measures of pulmonary function, including forced expiratory volume in one second (FEV1), forced vital capacity, and their ratio. However, variants with lower minor allele frequencies are less explored. We conducted a large-scale gene-smoking interaction meta-analysis on exonic rare and low-frequency variants involving 44,429 individuals of European ancestry in the discovery stage and sought replication in the UK BiLEVE study with 45,133 European ancestry samples and UK Biobank study with 59,478 samples. We leveraged data on cigarette smoking, the major environmental risk factor for reduced lung function, by testing gene-by-smoking interaction effects only and simultaneously testing the genetic main effects and interaction effects. The most statistically significant signal that replicated was a previously reported low-frequency signal in GPR126, distinct from common variant associations in this gene. Although only nominal replication was obtained for a top rare variant signal rs142935352 in one of the two studies, interaction and joint tests for current smoking and PDE3B were significantly associated with FEV1. This study investigates the utility of assessing gene-by-smoking interactions and underscores their effects on potential pulmonary function.Clinical epidemiolog

Improving reading achievements of struggling learners

In The Netherlands, the percentage of struggling readers in the 1st year of formal reading instruction is about 25%. This problem inspired us to develop the Reading Acceleration Programme. To evaluate the effectiveness of this programme, a quasi-experiment is carried out. The teachers in the experimental group have been trained to improve their core instruction, to broaden their instruction for struggling learners, and to implement special measures for pupils who do not respond sufficiently to these interventions. A significant difference was found on the post-tests for measuring reading of single words and reading whole sentences, after correcting for pre-test, age, intelligence, socioeconomic status, and ethnic minority. Furthermore, the programme turned out to reduce the percentage of struggling readers in the experimental group from over 28% to less than 6%. In the follow-up study, the overall effects remained to a moderate degree