Although a large number of studies have investigated the possible effect of polymorphisms of the renin–angiotensin–aldosterone system (RAAS) in arterial hypertension, most of the published results do not provide a clear picture of the effect of each individual gene taken alone or in combination. In the October issue of the journal, the GENIPER Project’s investigators [1] tested this effect in a large number of carefully selected hypertensive subjects and controls (n= 2461) recruited in 13 Italian centres. They found small, but statistically significant, associations with similar trends in the several Italian regions. More interestingly, they provide arguments for an additive effect of the individual variants of the genes studied, although no synergistic interaction was observed. As in other studies addressing the possible relationships between genetic polymorphisms and complex traits, several questions need to be asked to evaluate the strengths and limitations of the presented results. Is the study reliable in its setting and its results? In case of replication, how do these results compare to those already published in the literature? What is their contribution to the available scientific knowledge?

One of the main issues related to case–control studies is statistical power. This power is not evaluated in most reports despite the fact that its computation is not difficult [2]. Evaluation of statistical power is important because studies testing the replication of a given association in independent samples are not often satisfying the level of power required to detect the initially described association, as demonstrated by Lalouel and Rohrwasser for the angiotensinogen (AGT) gene [3]. Statistical power depends not only on the number of cases and controls, but also on each allele frequency and on the a priori genetic hypothesis on the mode of