Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies.

Considerable experimental and epidemiological evidence suggests that elevated endogenous sex steroids -notably androgens and oestrogens -promote breast tumour development. In spite of this evidence, postmenopausal androgen replacement therapy with dehydroepiandrosterone (DHEA) or testosterone has been advocated for the prevention of osteoporosis and improved sexual wellbeing. We have conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition. Levels of DHEA sulphate (DHEAS), (D4-androstenedione), testosterone, oestrone, oestradiol and sex-hormone binding globulin (SHBG) were measured in prediagnostic serum samples of 677 postmenopausal women who subsequently developed breast cancer and 1309 matched control subjects. Levels of free testosterone and free oestradiol were calculated from absolute concentrations of testosterone, oestradiol and SHBG. Logistic regression models were used to estimate relative risks of breast cancer by quintiles of hormone concentrations. For all sex steroidsthe androgens as well as the oestrogens -elevated serum levels were positively associated with breast cancer risk, while SHBG levels were inversely related to risk. For the androgens, relative risk

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Objective: To describe anthropometric characteristics of participants of the European Prospective Investigation into Cancer and Nutrition (EPIC). Design: A cross-sectional analysis of baseline data of a European prospective cohort study. Subjects: This analysis includes study populations from 25 centres in nine European countries. The British populations comprised both a population-based and a 'healthconscious' group. The analysis was restricted to 83 178 men and 163 851 women aged 50 -64 years, this group being represented in all centres. Methods: Anthropometric examinations were undertaken by trained observers using standardised methods and included measurements of weight, height, and waist and hip circumferences. In the 'health-conscious' group (UK), anthropometric measures were predicted from self-reports. Results: Except in the 'health-conscious' group (UK) and in the French centres, mean body mass index (BMI) exceeded 25.0 kg m 22 . The prevalence of obesity (BMI $ 30 kg m 22 ) varied from 8% to 40% in men, and from 5% to 53% in women, with high prevalences (. 25%) in the centres from Spain, Greece, Ragusa and Naples (Italy) and the lowest prevalences (,10%) in the French centres and the 'healthconscious' group (UK). The prevalence of a large waist circumference or a high waistto-hip ratio was high in centres from Spain, Greece, Ragusa and Naples (Italy) and among women from centres in Germany and Bilthoven (The Netherlands). Conclusions: Anthropometric measures varied considerably within the EPIC population. These data provide a strong base for further investigation of anthropometric measures in relation to the risk of chronic diseases, especially cancer.

Objective: To examine the seroprevalence, correlates, and characteristics of undetected coeliac disease in a large adult population sample in Cambridge, UK. Methods: The Cambridge General Practice Health Study invited individuals from 12 general practices, aged 45-76 years, to attend for a health survey that included a bone density measurement, between 1990 and 1995. A total of 7550 participants' serum samples were tested for antiendomysial antibody (EMA). Seroprevalence of undetected coeliac disease was based on EMA positivity. Differences between EMA positive and negative participants of various physiological correlates and reported characteristics were estimated by multivariate logistic and linear regression and adjusted for age, sex, social class, and smoking behaviour. Results: The seroprevalence of undetected coeliac disease in this general population sample aged 45-76 was 1.2% (95% confidence interval (CI) 0.9-1.4). EMA positive participants (n=87) were on average slightly lighter by 2.2 kg (p=0.08), were more likely to have reported their general health as being "good or excellent" (odds ratio (OR) 1.76 (95% CI 0.90-3.46)), and were less likely to report being a current smoker (OR for current versus never 0.36 (95% CI 0.14-0.90)) than EMA negative participants. EMA positivity was associated with an 8% reduction in mean serum cholesterol (0.5 mmol/l; p<0.01) and reductions in mean haemoglobin (0.3 g/dl; p<0.01), total protein (1.0 g/l; p<0.05), and corrected serum calcium (0.02 mmol/l; p<0.05). There was an increased risk of osteoporosis in EMA positive participants (OR 3.1 (95% CI 1.3-7.2)) and of mild anaemia (OR 4.6 (95% CI 2.5-8.2)) compared with EMA negative participants. Conclusions: Undetected coeliac disease is likely to affect approximately 1% of the population of England aged 45-76 years, a value similar to several other countries. Those affected report "better health" but they do have an increased risk of osteoporosis and mild anaemia. In contrast, they have a favourable cardiovascular risk profile that may afford protection from ischaemic heart disease and stroke.