Suzy Oakes

Bio: Suzy Oakes is an academic researcher from University of Cambridge. The author has contributed to research in topics: Population & Prospective cohort study. The author has an hindex of 19, co-authored 22 publications receiving 5047 citations. Previous affiliations of Suzy Oakes include Cambridge University Hospitals NHS Foundation Trust.

Glycated haemoglobin, diabetes, and mortality in men in Norfolk cohort of european prospective investigation of cancer and nutrition (EPIC-Norfolk).

Abstract: Objective To examine the value of glycated haemoglobin (HbA1c) concentration, a marker of blood glucose concentration, as a predictor of death from cardiovascular and all causes in men. Design Prospective population study. Setting Norfolk cohort of European Prospective Investigation into Cancer and Nutrition (EPIC›Norfolk). Subjects 4662 men aged 45›79 years who had had glycated haemoglobin measured at the baseline survey in 1995›7 who were followed up to December 1999. Main outcome measures Mortality from all causes, cardiovascular disease, ischaemic heart disease, and other causes. Results Men with known diabetes had increased mortality from all causes, cardiovascular disease, and ischaemic disease (relative risks 2.2, 3.3, and 4.2, respectively, P < 0.001 independent of age and other risk factors) compared with men without known diabetes. The increased risk of death among men with diabetes was largely explained by HbA1c concentration. HbA1c was continuously related to subsequent all cause, cardiovascular, and ischaemic heart disease mortality through the whole population distribution, with lowest rates in those with HbA1c concentrations below 5%. An increase of 1% in HbA1c was associated with a 28% (P < 0.002) increase in risk of death independent of age, blood pressure, serum cholesterol, body mass index, and cigarette smoking habit; this effect remained (relative risk 1.46, P = 0.05

Validation of dietary assessment methods in the UK arm of EPIC using weighed records, and 24-hour urinary nitrogen and potassium and serum vitamin C and carotenoids as biomarkers.

Abstract: Background In the UK EPIC validation studies, the accuracy of several methods was assessed by comparison with to-day weighed records and the biomarkers, 24-hour urine nitrogen (N) and potassium (K), plasma carotenoids and plasma vitamin C. Methods Comparisons between methods were made on 156 women, studied over 1 year at 3-monthly intervals at home. On each of four occasions, volunteers completed 4 days of weighed records and provided two 24-hour urine collections and a fasting blood sample. Results In comparison with the 16 days of weighed records, a food frequency questionnaire (FFQ) yielded higher values mainly due to greater reported consumption of milk and of vegetables. A 24-hour recall was as good as the FFQ in placing individuals in the distribution of habitual diet from weighed records. Results obtained from a 7-day estimated record were closest to those obtained from the weighed record. Correlations between 24-hour urine excretion and dietary N intake from weighed records were high (0.78-0.87) as were those with estimated food diaries (0.60-0.70). Correlations between urine N and the FFQ and 24-hour recall were lower (0.10 to 0.27), but improved by energy adjustment using residuals for N and K which are correlated with total energy intake. Comparisons between dietary estimates and urinary K and serum carotenoids and vitamin C showed broadly similar results. Limited biomarker information amongst 200 UK EPIC participants supported the findings of the validation study. Conclusions UK EPIC uses three methods (the 7-day diary, an improved FFQ, and the 24-hour recall) to assess diet. 93% of first food diaries are returned completed by participants. Repeated diaries are the main dietary assessment method for nested case-control analyses.

Nutritional methods in the European Prospective Investigation of Cancer in Norfolk

Abstract: Objective: To describe methods and dietary habits of a large population cohort. Design: Prospective assessment of diet using diet diaries and food-frequency questionnaires, and biomarkers of diet in 24-h urine collections and blood samples. Setting: Free living individuals aged 45 to 75 years living in Norfolk, UK. Subjects: Food and nutrient intake from a food-frequency questionnaire on 23 003 men and women, and from a 7-day diet diary from 2117 men and women. Nitrogen, sodium and potassium excretion was obtained from single 24-h urine samples from 300 individuals in the EPIC cohort. Plasma vitamin C was measured for 20 846 men and women. Results: The food-frequency questionnaire (FFQ) and the food diary were able to determine differences in foods and nutrients between the sexes and were reliable as judged by repeated administrations of each method. Plasma vitamin C was significantly higher in women than men. There were significant OP , 0:001U differences in mean intake of all nutrients measured by the two different methods in women but less so in men. The questionnaire overestimated dairy products and vegetables in both men and women when compared with intakes derived from the diary, but underestimated cereal and meat intake in men. There were some consistent trends with age in food and nutrient intakes assessed by both methods, particularly in men. Correlation coefficients between dietary intake assessed from the diary and excretion of nitrogen and potassium in a single 24-h urine sample ranged from 0.36 to 0.47. Those comparing urine excretion and intake assessed from the FFQ were 0.09 to 0.26. The correlations between plasma vitamin C and dietary intake from the first FFQ, 24-h recall or diary were 0.28, 0.35 and 0.40. Conclusions: EPIC Norfolk is one of the largest epidemiological studies of nutrition in the UK and the largest on which plasma vitamin C has been obtained. Methods for obtaining food and nutrient intake are described in detail. The results shown here for food and nutrient intakes can be compared with results from other population studies utilising different methods of assessing dietary intake. The utility of different methods used in different settings within the main EPIC cohort is described. The FFQ is to be used particularly in pooled analyses of risk from diet in relation to cancer incidence within the larger European EPIC study, where measurement error is more likely to be overcome by large dietary heterogeneity on an international basis. Findings in the UK, where dietary variation between individuals is smaller and hence the need to use a more accurate individual method greater, will be derived from the 7-day diary information on a nested case‐control basis. 24-h recalls can be used in the event that diary information should not be forthcoming from some eventual cases. Combinations of results utilising all dietary methods and biomarkers may also be possible.

‘Mendelian randomization’: can genetic epidemiology contribute to understanding environmental determinants of disease?

Abstract: Associations between modifiable exposures and disease seen in observational epidemiology are sometimes confounded and thus misleading, despite our best efforts to improve the design and analysis of studies. Mendelian randomization-the random assortment of genes from parents to offspring that occurs during gamete formation and conception-provides one method for assessing the causal nature of some environmental exposures. The association between a disease and a polymorphism that mimics the biological link between a proposed exposure and disease is not generally susceptible to the reverse causation or confounding that may distort interpretations of conventional observational studies. Several examples where the phenotypic effects of polymorphisms are well documented provide encouraging evidence of the explanatory power of Mendelian randomization and are described. The limitations of the approach include confounding by polymorphisms in linkage disequilibrium with the polymorphism under study, that polymorphisms may have several phenotypic effects associated with disease, the lack of suitable polymorphisms for studying modifiable exposures of interest, and canalization-the buffering of the effects of genetic variation during development. Nevertheless, Mendelian randomization provides new opportunities to test causality and demonstrates how investment in the human genome project may contribute to understanding and preventing the adverse effects on human health of modifiable exposures.

Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index

Abstract: Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and similar to 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 x 10(-8)), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.

Discovery and refinement of loci associated with lipid levels

Abstract: Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 × 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.

Genome-wide association study identifies novel breast cancer susceptibility loci

Abstract: Breast cancer exhibits familial aggregation, consistent with variation in genetic susceptibility to the disease. Known susceptibility genes account for less than 25% of the familial risk of breast cancer, and the residual genetic variance is likely to be due to variants conferring more moderate risks. To identify further susceptibility alleles, we conducted a two-stage genome-wide association study in 4,398 breast cancer cases and 4,316 controls, followed by a third stage in which 30 single nucleotide polymorphisms (SNPs) were tested for confirmation in 21,860 cases and 22,578 controls from 22 studies. We used 227,876 SNPs that were estimated to correlate with 77% of known common SNPs in Europeans at r2.0.5. SNPs in five novel independent loci exhibited strong and consistent evidence of association with breast cancer (P,1027). Four of these contain plausible causative genes (FGFR2, TNRC9, MAP3K1 and LSP1). At the second stage, 1,792 SNPs were significant at the P,0.05 level compared with an estimated 1,343 that would be expected by chance, indicating that many additional common susceptibility alleles may be identifiable by this approach.