Genome-wide association study of response to cognitive behavioural therapy in children with anxiety disorders

Background Anxiety disorders are common, and cognitive–behavioural therapy (CBT) is a first-line treatment. Candidate gene studies have suggested a genetic basis to treatment response, but findings have been inconsistent. Aims To perform the first genome-wide association study (GWAS) of psychological treatment response in children with anxiety disorders (n = 980). Method Presence and severity of anxiety was assessed using semi-structured interview at baseline, on completion of treatment (post-treatment), and 3 to 12 months after treatment completion (follow-up). DNA was genotyped using the Illumina Human Core Exome-12v1.0 array. Linear mixed models were used to test associations between genetic variants and response (change in symptom severity) immediately post-treatment and at 6-month follow-up. Results No variants passed a genome-wide significance threshold (P = 5×10−8) in either analysis. Four variants met criteria for suggestive significance (P<5×10−6) in association with response post-treatment, and three variants in the 6-month follow-up analysis. Conclusions This is the first genome-wide therapygenetic study. It suggests no common variants of very high effect underlie response to CBT. Future investigations should maximise power to detect single-variant and polygenic effects by using larger, more homogeneous cohorts.

Sensory and consumer science methods used with older adults: a review of current methods and recommendations for the future

Capturing the sensory perception and preferences of older adults, whether healthy or with particular disease states, poses major methodological challenges for the sensory community. Currently a vastly under researched area, it is at the same time a vital area of research as alterations in sensory perception can affect daily dietary food choices, intake, health and wellbeing. Tailored sensory methods are needed that take into account the challenges of working with such populations including poor access leading to low patient numbers (study power), cognitive abilities, use of medications, clinical treatments and context (hospitals and care homes). The objective of this paper was to review current analytical and affective sensory methodologies used with different cohorts of healthy and frail older adults, with focus on food preference and liking. We particularly drew attention to studies concerning general ageing as well as to those considering age-related diseases that have an emphasis on malnutrition and weight loss. Pubmed and Web of Science databases were searched to 2014 for relevant articles in English. From this search 75 papers concerning sensory acuity, 41 regarding perceived intensity and 73 relating to hedonic measures were reviewed. Simpler testing methods, such as directional forced choice tests and paired preference tests need to be further explored to determine whether they lead to more reliable results and better inter-cohort comparisons. Finally, sensory quality and related quality of life for older adults suffering from dementia must be included and not ignored in our future actions.

A comprehensive meta-analysis of common genetic variants in autism spectrum conditions

Background Autism spectrum conditions (ASC) are a group of neurodevelopmental conditions characterized by difficulties in social interaction and communication alongside repetitive and stereotyped behaviours. ASC are heritable, and common genetic variants contribute substantial phenotypic variability. More than 600 genes have been implicated in ASC to date. However, a comprehensive investigation of candidate gene association studies in ASC is lacking. Methods In this study, we systematically reviewed the literature for association studies for 552 genes associated with ASC. We identified 58 common genetic variants in 27 genes that have been investigated in three or more independent cohorts and conducted a meta-analysis for 55 of these variants. We investigated publication bias and sensitivity and performed stratified analyses for a subset of these variants. Results We identified 15 variants nominally significant for the mean effect size, 8 of which had P values below a threshold of significance of 0.01. Of these 15 variants, 11 were re-investigated for effect sizes and significance in the larger Psychiatric Genomics Consortium dataset, and none of them were significant. Effect direction for 8 of the 11 variants were concordant between both the datasets, although the correlation between the effect sizes from the two datasets was poor and non-significant. Conclusions This is the first study to comprehensively examine common variants in candidate genes for ASC through meta-analysis. While for majority of the variants, the total sample size was above 500 cases and 500 controls, the total sample size was not large enough to accurately identify common variants that contribute to the aetiology of ASC.

Pension scheme redesign and wealth redistribution between the members and sponsor: the USS rule change in October 2011

The redesign of defined benefit pension schemes usually results in a substantial redistribution of wealth between age cohorts of members, pensioners, and the sponsor. This is the first study to quantify the redistributive effects of a rule change by a real world scheme (the Universities Superannuation Scheme, USS) where the sponsor underwrites the pension promise. In October 2011 USS closed its final salary scheme to new members, opened a career average revalued earnings (CARE) section, and moved to ‘cap and share’ contribution rates. We find that the pre-October 2011 scheme was not viable in the long run, while the post-October 2011 scheme is probably viable in the long run, but faces medium term problems. In October 2011 future members of USS lost 65% of their pension wealth (or roughly £100,000 per head), equivalent to a reduction of roughly 11% in their total compensation, while those aged over 57 years lost almost nothing. The riskiness of the pension wealth of future members increased by a third, while the riskiness of the present value of the sponsor’s future contributions reduced by 10%. Finally, the sponsor’s wealth increased by about £32.5 billion, equivalent to a reduction of 26% in their pension costs.