Background Depression is more common in obese than non-obese individuals, especially in women, but the causal relationship between obesity and depression is complex and uncertain. Previous studies have used genetic variants associated with BMI to provide evidence that higher body mass index (BMI) causes depression, but have not tested whether this relationship is driven by the metabolic consequences of BMI nor for differences between men and women. Methods We performed a Mendelian randomization study using 48 791 individuals with depression and 291 995 controls in the UK Biobank, to test for causal effects of higher BMI on depression (defined using self-report and Hospital Episode data). We used two genetic instruments, both representing higher BMI, but one with and one without its adverse metabolic consequences, in an attempt to ‘uncouple’ the psychological component of obesity from the metabolic consequences. We further tested causal relationships in men and women separately, and using subsets of BMI variants from known physiological pathways. Results Higher BMI was strongly associated with higher odds of depression, especially in women. Mendelian randomization provided evidence that higher BMI partly causes depression. Using a 73-variant BMI genetic risk score, a genetically determined one standard deviation (1 SD) higher BMI (4.9 kg/m2) was associated with higher odds of depression in all individuals [odds ratio (OR): 1.18, 95% confidence interval (CI): 1.09, 1.28, P = 0.00007) and women only (OR: 1.24, 95% CI: 1.11, 1.39, P = 0.0001). Meta-analysis with 45 591 depression cases and 97 647 controls from the Psychiatric Genomics Consortium (PGC) strengthened the statistical confidence of the findings in all individuals. Similar effect size estimates were obtained using different Mendelian randomization methods, although not all reached P < 0.05. Using a metabolically favourable adiposity genetic risk score, and meta-analysing data from the UK biobank and PGC, a genetically determined 1 SD higher BMI (4.9 kg/m2) was associated with higher odds of depression in all individuals (OR: 1.26, 95% CI: 1.06, 1.50], P = 0.010), but with weaker statistical confidence. Conclusions Higher BMI, with and without its adverse metabolic consequences, is likely to have a causal role in determining the likelihood of an individual developing depression.

Background The three main alleles of the APOE gene (ε4, ε3 and ε2) carry differential risks for conditions including Alzheimer's disease (AD) and cardiovascular disease. Due to their clinical significance, we explored disease associations of the APOE genotypes using a hypothesis-free, data-driven, phenome-wide association study (PheWAS) approach. Methods We used data from the UK Biobank to screen for associations between APOE genotypes and over 950 disease outcomes using genotype ε3ε3 as a reference. Data was restricted to 337,484 white British participants (aged 37–73 years). Findings After correction for multiple testing, PheWAS analyses identified associations with 37 outcomes, representing 18 distinct diseases. As expected, ε3ε4 and ε4ε4 genotypes associated with increased odds of AD (p ≤ 7.6 × 10 −46 ), hypercholesterolaemia (p ≤ 7.1 × 10 −17 ) and ischaemic heart disease (p ≤ 2.3 × 10 −4 ), while ε2ε3 provided protection for the latter two conditions (p ≤ 3.7 × 10 −10 ) compared to ε3ε3. In contrast, ε4-associated disease protection was seen against obesity, chronic airway obstruction, type 2 diabetes, gallbladder disease, and liver disease (all p ≤ 5.2 × 10 −4 ) while ε2ε2 homozygosity increased risks of peripheral vascular disease, thromboembolism, arterial aneurysm, peptic ulcer, cervical disorders, and hallux valgus (all p ≤ 6.1 × 10 −4 ). Sensitivity analyses using brain neuroimaging, blood biochemistry, anthropometric, and spirometric biomarkers supported the PheWAS findings on APOE associations with respective disease outcomes. Interpretation PheWAS confirms strong associations between APOE and AD, hypercholesterolaemia, and ischaemic heart disease, and suggests potential ε4-associated disease protection and harmful effects of the ε2ε2 genotype, for several conditions. Funding National Health and Medical Research Council of Australia.

BackgroundAbout one-third of the world’s population lack access to essential medicines and this is further compounded by inappropriate prescription, dispensing, sale and use of the available medicines. The objective of the study was to assess the patterns of medicine use among health facilities in eastern Ethiopia using World Health Organization’s Prescribing, Patient Care and Health facility indicators.MethodsA cross sectional study was carried out in eight randomly selected health centers and data were collected retrospectively as well as prospectively. Prescribing indicators were assessed retrospectively using 636 prescriptions selected by systematic random sampling technique among prescriptions filled between September 2013 and September 2014. Patient care indicators were assessed prospectively by interviewing 708 patients from the health facilities. Health facilities were assessed through observation. Data were entered and analyzed using Statistical Packages for Social Sciences version 20. P-value less than 0.05 at 95 % confidence interval considered for significance of relationships for associations in statistical tests.ResultsThe average number of medicines per prescription was 2.2 with standard deviation of 0.8. The proportion of medicines prescribed by generic name was 97 and 92 % of the prescribed medicines were included in List of Essential Medicines for Ethiopia, Prescriptions containing antibiotics and injections constituted (82.5 and 11.2 %) respectively. Of the total of 1426 medicines prescribed, 49.6 % were antibiotics, with amoxicillin (33.3 %) and co-trimoxazole (16.0 %) being the most commonly prescribed agents. The average consultation and dispensing times were 5.6 and 2.7 min, respectively. Among the medicines dispensed, 64.0 % were adequately labeled and the proportion of patients with adequate knowledge about medicines was 69 %.ConclusionThe prescribing and dispensing practices in the health facilities are fairly good and are not that far from the standard WHO requirements. However, there is a need to do more on some issues, including prescribing practice of antibiotics, average number of medicines per prescription, and patients’ dosage form knowledge.Electronic supplementary materialThe online version of this article (doi:10.1186/s12913-016-1414-6) contains supplementary material, which is available to authorized users.