Is adolescent body mass index and waist circumference associated with the food environments surrounding schools and homes? A longitudinal analysis

Background: There has been considerable interest in the role of access to unhealthy food options as a determinant of weight status. There is conflict across the literature as to the existence of such an association, partly due to the dominance of cross-sectional study designs and inconsistent definitions of the food environment. The aim of our study is to use longitudinal data to examine if features of the food environment are associated to measures of adolescent weight status. Methods: Data were collected from secondary schools in Leeds (UK) and included measurements at school years 7 (ages 11/12), 9 (13/14), and 11 (15/16). Outcome variables, for weight status, were standardised body mass index and standardised waist circumference. Explanatory variables included the number of fast food outlets, supermarkets and ‘other retail outlets’ located within a 1 km radius of an individual’s home or school, and estimated travel route between these locations (with a 500 m buffer). Multi-level models were fit to analyse the association (adjusted for confounders) between the explanatory and outcome variables. We also examined changes in our outcome variables between each time period. Results: We found few associations between the food environment and measures of adolescent weight status. Where significant associations were detected, they mainly demonstrated a positive association between the number of amenities and weight status (although effect sizes were small). Examining changes in weight status between time periods produced mainly non-significant or inconsistent associations. Conclusions: Our study found little consistent evidence of an association between features of the food environment and adolescent weight status. It suggests that policy efforts focusing on the food environment may have a limited effect at tackling the high prevalence of obesity if not supported by additional strategies

Investigation of common, low-frequency and rare genome-wide variation in anorexia nervosa

Anorexia nervosa (AN) is a complex neuropsychiatric disorder presenting with dangerously low body weight, and a deep and persistent fear of gaining weight. To date, only one genome-wide significant locus associated with AN has been identified. We performed an exome-chip based genome-wide association studies (GWAS) in 2158 cases from nine populations of European origin and 15 485 ancestrally matched controls. Unlike previous studies, this GWAS also probed association in low-frequency and rare variants. Sixteen independent variants were taken forward for in silico and de novo replication (11 common and 5 rare). No findings reached genome-wide significance. Two notable common variants were identified: rs10791286, an intronic variant in OPCML (P=9.89 × 10−6), and rs7700147, an intergenic variant (P=2.93 × 10−5). No low-frequency variant associations were identified at genome-wide significance, although the study was well-powered to detect low-frequency variants with large effect sizes, suggesting that there may be no AN loci in this genomic search space with large effect sizes

A case-only study to identify genetic modifiers of breast cancer risk for <em>BRCA1/BRCA2</em> mutation carriers

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P &lt; 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers