Sick genes, sick individuals or sick populations with chronic disease? The emergence of diabetes and high blood pressure in African-origin populations

Aim and Methods. To discuss evidence for and against genetic 'causes' of type 2 diabetes, illustrated by standardized study of glucose intolerance and high blood pressure in four representative African origin populations. Comparison of two genetically closer sites: rural (site I) and urban Cameroon (2); then Jamaica (3) and Caribbean migrants to Britain (80% from Jamaica-4). Background. Alternatives to the reductionist search for genetic 'causes' of chronic disease include Rose's concept that populations give rise to 'sick' individuals. Twin studies offer little support to genetic hypotheses because monozygotic twins share more than genes in utero and suffer from ascertainment bias. Non-genetic intergenerational mechanisms include amniotic fluid growth factors and maternal exposures. Type 2 diabetes and hypertension incidence accelerate in low-risk European populations from body mass ≥23 kg/m2, well within 'desirable' limits. Transition from subsistence agriculture in West Africa occurred this century and from western hemisphere slavery only six generations ago, with slow escape from intergenerational poverty since. Results. 'Caseness' increased clearly within and between genetically similar populations: age-adjusted diabetes rates were 0.8, 2.4, 8.5 and 16.4% for sites 1-4, respectively; for 'hypertension', rates were 7, 16, 21 and 34%, with small shifts in risk factors. Body mass index rose similarly. Conclusion. Energy imbalance and intergenerational socioeconomic influences are much more likely causes of diabetes (and most chronic disease) than ethnic/genetic variation, which does occur, poorly related to phenotype. The newer method of 'proteomics' holds promise for identifying environmental triggers influencing gene products. Even in lower prevalence 'westernized' societies, genetic screening per se for diabetes/chronic disease is likely to be imprecise and inefficient hence unreliable and expensive.