Systematic review of birth cohort studies in Africa

In sub-Saharan Africa, unacceptably high rates of mortality amongst women and children continue to persist. The emergence of research employing new genomic technologies is advancing knowledge on cause of disease. This review aims to identify birth cohort studies conducted in sub-Saharan Africa and to consider their suitability as a platform to support genetic epidemiological studies

From Genomic Advances to Public Health Benefits: The Unbearable Lightness of Being Stuck

Genetic determinants of common human diseases are still poorly understood. Due to large investments, many small successes have been made and the research field is rapidly expanding. However, genetic susceptibility variants showing repeatable associations with common diseases are usually of small effect. They are therefore unlikely to individually explain substantial share of disease burden in any community or provide new insights into disease pathogenesis that could lead to development of new drugs effective in considerable portion of the disease cases in a population. Genetic architecture of common diseases is beginning to reveal an incredible diversity of potential genetic causes that act through somewhat limited number of mechanisms with important contribution of environmental interactions. In light of these findings, we present current understanding of genetic architecture of a spectrum of human diseases. We address the encountered problems in susceptibility gene identification, review the success of leading gene identification strategies and discuss current prospects for translating genomic advances into measurable public health benefits

Health Effects of Human Population Isolation and Admixture

There are occasions when, either by choice or by circumstances, human beings are driven to temporary or permanent isolation from other people. Some of the examples are working in a lighthouse, serving a prison sentence, or doing research in less populated areas. The same can happen to entire human populations, although this may seem quite improbable in an era which provides ever-increasing means of communication and transport. However, the gap between those who have access to these technological advancements and those who do not is increasingly widening. The number of people living in isolated communities, and whose isolation from other populations is constantly increasing, is largely underestimated

Effects of inbreeding on human quantitative traits and complex common diseases of late-onset

Studying the effects of inbreeding in human populations could provide insights into the genetic architecture of medically relevant quantitative traits and common complex diseases of late onset. In a historic example of 2,761 examinees from isolated village populations of the islands of Brae, Hvar and Korcula, Croatia, collected through field work undertaken in the 1970's and 1980's, individual inbreeding coefficients were computed based on genealogical records. Inbreeding showed a strong positive effect on blood pressure and negative on cortical index. The 14 villages were revisited in 2000 to assess the prevalence of learning disability and of common complex diseases of late onset. A cohort study and an ecological study, after appropriate standardization, both showed that inbreeding increased the prevalence of coronary heart disease, stroke, psychiatric disorders, cancer, gout, asthma, glaucoma and peptic ulcer, but not type II diabetes. A strong effect on the prevalence of learning disability was also noted in 10 villages. In a followup study on 1,001 examinees from 10 other villages sampled on neighbouring islands in 2002, positive effects of outbreeding on fitness, height, blood pressure, cholesterol and triglyceride values were detected. The possible explanations for the observed effects include: (i) The joint effect of inbreeding depression on all polygenic quantitative phenotypes that confer risk for lateonset diseases is predicted to be multiplicative rather than additive, (ii) The "genetic load" of rare "Mendelian" variants with large deleterious effects in post-reproductive adults is unknown, but could be much greater than expected as these variants were invisible to selection through human history, (iii) Deleterious effects resulting from autozygosity in hundreds of affected rare recessive variants of small effect under common disease/rare variant (CD/RV) hypothesis could result in epistatic effects that could jointly impair the capacity to compensate against environmental risks, (iv) Heterozygote advantage in loci under balancing selection could be reduced by inbreeding. Consanguinity is common in many populations and the possible effects of inbreeding depression on disease burden and reduced life expectancy should be further investigated