Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, we conducted genome-wide association meta-analyses of waist and hip circumference-related traits in up to 224,459 individuals. We identified 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (WHRadjBMI) and an additional 19 loci newly associated with related waist and hip circumference measures (P<5×10−8). Twenty of the 49 WHRadjBMI loci showed significant sexual dimorphism, 19 of which displayed a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation, and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

Objective To examine whether adherence to the modified Mediterranean diet, in which unsaturates were substituted for monounsaturates, is associated with longer life expectancy among elderly Europeans. Design Multicentre, prospective cohort study. Setting Nine European countries

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The European Prospective Investigation into Cancer and Nutrition (EPIC), which covers a large cohort of half a million men and women from 23 European centres in 10 Western European countries, was designed to study the relationship between diet and the risk of chronic diseases, particularly cancer. Information on usual individual dietary intake was assessed using different validated dietary assessment methods across participating countries. In order to adjust for possible systematic over-or underestimation in dietary intake measurements and correct for attenuation bias in relative risk estimates, a calibration approach was developed. This approach involved an additional dietary assessment common across study populations to re-express individual dietary intakes according to the same reference scale. A single 24-hour diet recall was therefore collected, as the EPIC reference calibration method, from a stratified random sample of 36 900 subjects from the entire EPIC cohort, using a software program (EPIC-SOFT) specifically designed to standardise the dietary measurements across study populations. This paper describes the design and populations of the calibration sub-studies set up in the EPIC centres. In addition, to assess whether the calibration sub-samples were representative of the entire group of EPIC cohorts, a series of subjects' characteristics known possibly to influence dietary intakes was compared in both population groups. This was the first time that calibration sub-studies had been set up in a large multi-centre European study. These studies showed that, despite certain inherent methodological and logistic constraints, a study design such as this one works relatively well in practice. The average response in the calibration study was 78.3% and ranged from 46.5% to 92.5%. The calibration population differed slightly from the overall cohort but the differences were small for most characteristics and centres. The overall results suggest that, after adjustment for age, dietary intakes estimated from calibration samples can reasonably be interpreted as representative of the main cohorts in most of the EPIC centres.

Objectives: To evaluate the reproducibility of, and to compare and calibrate, diet measures by the Northern Sweden 84-item food-frequency questionnaire (FFQ) with measures from 24-hour diet recalls (24-HDR). Design: Randomly selected respondents ðn ¼ 246Þ from the EPIC (diet-cancer) and MONICA (diet -cardiovascular disease) study cohort in Northern Sweden were invited to answer the FFQ twice over a one-year interval (FFQ1 and FFQ2), and to complete ten 24-hour recalls (reference method) in the months between. Plasma b-carotene concentrations were determined from a subset of 47 participants. Setting: Västerbotten and Norrbotten, Northern Sweden. Participants: Ninety-six men and 99 women, who completed the study. Results: The reproducibility of the FFQ was high in terms of both mean energy and nutrient intakes and relative ranking of participants by intake levels (median Pearson correlation of 0.68). Moderately higher food intake frequencies were recorded by FFQ1 compared with 24-hour recalls for dairy products, bread/cereals, vegetables, fruits and potato/rice/pasta, whereas meat, fish, sweet snacks and alcoholic beverage intakes were lower. The median Spearman coefficient of correlation between FFQ1 and the average of ten 24-HDR measurements was 0.50. Daily energy and nutrient intakes were similar for FFQ1 and 24-HDR measurements, except for fibre, vitamin C, b-carotene and retinol (FFQ1 . 24-HDR) and sucrose and cholesterol ðFFQ1 , 24-HDRÞ: Pearson coefficients of correlation between FFQ1 and 24-HDR corrected for attenuation due to residual day-to-day variation in the 24-HDR measurements ranged from 0.36 to 0.79 (median 0.54). Adjustment for energy had only very moderate effects on the correlation estimates. Calibration coefficients estimated by linear regression of the 24-HDR on the FFQ1 measurements varied between 0.30 and 0.59 for all nutrients except alcohol, which had calibration coefficients close to 1.0. These low calibration coefficients indicate that relative risk estimates corresponding to an absolute difference in dietary intake levels measured by the FFQ will generally be biased towards 1.0. Plasma b-carotene levels had a Pearson coefficient of correlation of 0.47 with the 24-HDR measurements, and of 0.23 with FFQ1 measurements. Conclusions: The Northern Sweden FFQ measurements have good reproducibility and an estimated level of validity similar to that of FFQ measurements in other prospective cohort studies. The results from this study will form the basis for the correction of attenuation and regression dilution biases in relative risk estimates, in future studies relating FFQ measurements to disease outcomes.

Objective: The aims of the present study were (1) to evaluate the degree to which underreporting of energy intake by repeated 24-hour recalls was related to gender, age, weight status, day of interview, educational level, smoking habits and area of living, and (2) to compare the dietary characteristics of underreporters with those of others. Design: Cross-sectional study. Ten 24-hour recalls were performed during a one-year period. Setting: The Va Èsterbotten intervention programme of cardiovascular disease and diabetes in Northern Sweden. Subjects: Ninety-four men and 99 women in four age groups: 30, 40, 50 and 60 years. Results: The prevalence of men and women with a food intake level (FIL; reported energy intake divided by estimated basal metabolic rate) below 1.2 was 44% and 47%, respectively. The youngest age group had higher FIL values than the oldest age group for both men (1.5 versus 1.1) and women (1.4 versus 1.1). The prevalence and magnitude of underreporting were directly related to body mass index (BMI; correlation coefficient: 20.47 (men) and 20.55 (women)). Smokers had a lower FIL value (1.1) than non-smokers (1.3). The nutrient density was lower for the group with high FIL values for protein and calcium and higher for fat and sucrose. The upper FIL group often had higher intake frequencies and larger portion sizes than the lower FIL group. Conclusions: Underreporting of energy intake is prevalent when 24-hour recalls are used, but the prevalence differs between sub-groups in the population. BMI was the main predictor of underreporting but also old age and smoking seem to contribute in this aspect. Socially desirable food items were not underreported to the same extent as socially undesirable food items. The intake frequencies and portion sizes partly explained the differences in FIL.

BackgroundRecently, some US cohorts have shown a moderate association between red and processed meat consumption and mortality supporting the results of previous studies among vegetarians. The aim of this study was to examine the association of red meat, processed meat, and poultry consumption with the risk of early death in the European Prospective Investigation into Cancer and Nutrition (EPIC).MethodsIncluded in the analysis were 448,568 men and women without prevalent cancer, stroke, or myocardial infarction, and with complete information on diet, smoking, physical activity and body mass index, who were between 35 and 69 years old at baseline. Cox proportional hazards regression was used to examine the association of meat consumption with all-cause and cause-specific mortality.ResultsAs of June 2009, 26,344 deaths were observed. After multivariate adjustment, a high consumption of red meat was related to higher all-cause mortality (hazard ratio (HR) = 1.14, 95% confidence interval (CI) 1.01 to 1.28, 160+ versus 10 to 19.9 g/day), and the association was stronger for processed meat (HR = 1.44, 95% CI 1.24 to 1.66, 160+ versus 10 to 19.9 g/day). After correction for measurement error, higher all-cause mortality remained significant only for processed meat (HR = 1.18, 95% CI 1.11 to 1.25, per 50 g/d). We estimated that 3.3% (95% CI 1.5% to 5.0%) of deaths could be prevented if all participants had a processed meat consumption of less than 20 g/day. Significant associations with processed meat intake were observed for cardiovascular diseases, cancer, and 'other causes of death'. The consumption of poultry was not related to all-cause mortality.ConclusionsThe results of our analysis support a moderate positive association between processed meat consumption and mortality, in particular due to cardiovascular diseases, but also to cancer.

Dental caries and periodontitis account for a vast burden of morbidity and healthcare spending, yet their genetic basis remains largely uncharacterized. Here, we identify self-reported dental disease proxies which have similar underlying genetic contributions to clinical disease measures and then combine these in a genome-wide association study meta-analysis, identifying 47 novel and conditionally-independent risk loci for dental caries. We show that the heritability of dental caries is enriched for conserved genomic regions and partially overlapping with a range of complex traits including smoking, education, personality traits and metabolic measures. Using cardio-metabolic traits as an example in Mendelian randomization analysis, we estimate causal relationships and provide evidence suggesting that the processes contributing to dental caries may have undesirable downstream effects on health.