The Fenland Study is a cohort of 12,435 participants born between 1950 and 1975 who have undergone detailed metabolic phenotyping with quantitative assessment of total and regional adiposity including ectopic fat deposition in the form of hepatic steatosis, using ultrasound and DEXA scanning. The recruitment of relatively young individuals before chronic disease onset was designed to investigate early processes and pathways to metabolic disease unaffected by therapy or co-existing disease. Fenland is one of the few cohorts with participants in young middle age, a gap noted in the recent MRC Strategic Review of UK Population Cohort Studies.
Key lifestyle determinants of metabolic disease have been characterised objectively. Resting metabolic rate and cardio-respiratory fitness have been measured, free-living physical activity energy expenditure estimated by combined heart rate and movement sensing and nutritional biomarker measurement undertaken. Metabolic phenotypes include a oral glucose tolerance test with measurement of insulin, c-peptide, insulin precursors, leptin and adiponectin. A GWAS (Genome-wide association study) of all individuals in the Fenland has been completed, and is contributing to investigations of the genetic basis of quantitative metabolic traits.
A follow up study is underway with the objective of studying the relationship between change in objectively quantified behaviours and body composition and metabolic risk. The Fenland study phase 2 (Fenland 2) is collecting longitudinal data on key risk factors and continuous metabolic traits, in order to define the temporal and dynamic relationships between these exposures and changes in metabolism, which are currently limited by the cross-sectional nature of Fenland 1.
Measurements carried out in Fenland 1 are being undertaken on the same cohort of participants in Fenland 2 in order to (a) investigate the determinants of change in metabolic and anthropometric variables and (b) to investigate the determinants of change in key lifestyle behaviours such as physical activity and dietary behaviour. In Fenland 2 we are collecting and storing mononuclear cells for the generation of induced pluripotent stem cells in order to enable us to study cellular processes in different tissues which could provide essential information used to infer mechanisms of, or predict risk for, metabolic diseases.
Fenland has enabled a number of sub-studies to be efficiently conducted. These have investigated: the effects of measurement of physical activity and feedback on awareness, behavioural intentions and physical activity levels (the Feedback, Awareness and Behaviour Study); the level of validity of conclusions of studies of physical activity by estimating the size of any reactivity effect (the Fenland Measurement Reactivity Trial); the effect of providing genetic or phenotypic risk estimates on objectively measured physical activity (the Diabetes Risk Communication Trial); and the effect of vitamin D supplementation in people at risk of diabetes (the Vitamin D Supplementation trial).
Dr Søren Brage
Dr Nita Forouhi
Professor Simon Griffin
Recruitment for phase 1 is complete, with analysis and publication also on-going. Genome-wide genotyping on the entire cohort and metabolomics measurement (using the Biocrates kit) was completed in 2015. Currently inviting participants back for phase 2 follow-up assessment.
The Fenland Study is led by the MRC Epidemiology Unit with responsibility for data and samples. Metabolomics measurement was undertaken in collaboration with MRC Human Nutrition Research.
The Fenland Study is core funded by the MRC. Metabolomics and extension of the GWAS analysis to cover the entire cohort was funded by the MRC Omics call (MC_PC_13046).
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