The past ten years have also demonstrated that accurate phenotyping is one of the keys to discover genetic determinants of disease. This may be less of an issue in relatively clearly defined diseases such as type 1 diabetes or Crohn's disease but is a major problem in hypertension where there is a somewhat arbitrary cut-off for definition of disease, marked sexual dimorphism, marked age effect, and a substantial influence of environmental factors. Unsurprisingly genetics of hypertension has been less of a success story compared to other common diseases, but the high impact of hypertension on cardiovascular morbidity and mortality more than justifies further efforts. The role of intermediate phenotypes including endothelial function and vascular stiffness but also associated phenotypes such as body weight and renal function [83] in gene discovery remains to be elucidated. It is also not clear whether an approach in the general population targeted towards blood pressure variation (quantitative trait) or an approach in selected extremes of cases and controls (quantitative trait) is superior. Most likely both approaches have their own merits.