The availability of very large open access human phenotype, electronic medical record and genotype resources is changing the way we can do research. Instead of focusing on a particular problem and gathering data to address that problem, we can now ask “what problems can we address given we have 1000s of datapoints in 100,000s of people?”

I will present some examples of our recent use of UK Biobank and other big human genetic resources to test hypotheses about genetic variation and mechanisms of disease, with a particular focus on obesity, body fat distribution and related traits. These examples include i) the characterisation of “favourable adiposity” alleles and their potential use to “uncouple” higher body fat from its adverse metabolic consequences; ii) advancing our understanding of gene x lifestyle interactions that are features of obesity, and iii) characterisation of the phenotypes associated with genetic variation, unbiased by any clinical selection, including X chromosome aneuploidy.