This is a prospective "recruit by genotype" cohort study that will test the role of several genetic variants (or combinations of variants) over a 4 year period (late 2014 to late 2018). The genetic variants will be chosen if there is strong evidence that they have a role in the pancreas and on insulin secretion. Each genetic variant will involve a different set of research volunteers and a slightly different set of tests. Participants will be blinded to their genetic variant status. Some genetic variants will be identified during the next 4 years so it is not possible to define at the outset a detailed methodology for all cohorts to be studied. This protocol has therefore been written to describe a core protocol relevant to the whole study, with appendices to describe specific cohorts within the study. Since the general management and ethical issues are overarching, as new genetic variants are identified over the 4 year study period, cohort-specific appendices will be added as major amendments, rather than submitting each cohort as a separate ethics application. The procedure for recruitment and testing of each set of research volunteers will be the same except for a component that will be outlined in cohort-specific appendices.