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

Aims and Methods To discuss evidence for and against genetic 'causes' of ty pe 2 diabetes, illustrated by standardized study of glucose intolerance and high blood pressure in four representative African origin populations. Com parison of two genetically closer sites: rural (site 1) 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 becau se monozygotic twins share more than genes in utero and suffer from ascerta inment bias. Non-genetic intergenerational mechanisms include amniotic flui d growth factors and maternal exposures. Type 2 diabetes and hypertension i ncidence accelerate in low-risk European populations from body mass greater than or equal to 23 kg/m(2), well within 'desirable' limits. Transition fr om subsistence agriculture in West Africa occurred this century and from we stern hemisphere slavery only six generations ago, with slow escape from in tergenerational 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 eth nic/genetic variation, which does occur, poorly related to phenotype. The n ewer method of 'proteomics' holds promise for identifying environmental tri ggers influencing gene products. Even in lower prevalence 'westernized' soc ieties, genetic screening per se for diabetes/chronic disease is likely to be imprecise and inefficient hence unreliable and expensive.