Genetic Predisposition Hypertension is a complex polygenic disorder in which many genes or gene combinations influence BP.S5.1-1,S5.1-2 Although several monogenic forms of hypertension have been identified, such as glucocorticoid-remediable aldosteronism, Liddle s syndrome, Gordon s syndrome, and others in which single- gene mutations fully explain the pathophysiology of hyper- tension, these disorders are rare.S5.1-3 The current tabulation of known genetic variants contributing to BP and hypertension includes more than 25 rare mutations and 120 single-nucleo- However, even with the discov- ery of multiple single-nucleotide polymorphisms influencing control of BP since completion of the Human Genome Project in 2003, the associated variants have only small effects. Indeed, at present, the collective effect of all BP loci identified through genome-wide association studies accounts for only about 3.5% of BP variability.S5.1-4 The presence of a high num- ber of small-effect alleles associated with higher BP results in a more rapid increase in BP with age.S5.1-5 Future studies will need to better elucidate genetic expression, epigenetic effects, transcriptomics, and proteomics that link genotypes with underlying pathophysiological mechanisms. 5.2. Environmental Risk Factors Various environmental exposures, including components of diet, physical activity, and alcohol consumption, influence BP. Many dietary components have been associated with Some of the diet-related factors associated with high BP include overweight and obesity, excess intake of sodium, and insufficient intake of potassium, calcium, magnesium, protein (especially from vegetables), fiber, and fish fats. Poor diet, physical inactivity, and excess intake of alcohol, alone or in combination, are the underlying cause of a large proportion of hypertension. Gut microbiota have also been linked to hypertension, especially in experimental Some of the best-proven environmental rela- tionships with high BP are briefly reviewed below, and non- pharmacological interventions to lower BP are discussed in Section 6.2. 5.2.1. 