Over the last decade of human genetics research, significant progress has been made regarding our understanding of genetic factors and their contribution to human health and disease. Unfortunately, this progress has mostly been made in populations of European ancestry, contributing to significant health disparity. This proposal aims to investigate similarities and differences in the contribution of genetic factors to human health and disease within and across ancestries. While our focus is on genetic factors, i.e., the genome, differences, and similarities in the phenome (i.e., the set of all traits expressed in humans) and the exposome (i.e., the set of all exposures of an individual across a lifetime) are also important. Especially the interplay between the three and how that interplay is modulated across different ancestries will help us better understand how prevention and intervention in the future should be shaped.
During the last decade of human genetics research, many loci have been associated with disease risk that only have a small effect on their own but, in concert, contribute significantly to the genetic liability of human traits (so-called polygenicity of traits). For example, this has now led to the situation that the combined effect of thousands of genetic loci explains a child’s height better than the average height of his parents. Both information pieces together, i.e., the genetic information and the information about the parent’s height, now allow us to predict a child’s height better than ever. Often loci that have risk or protective effects for one trait or phenotype also affect a wide range of similar or disparate phenotypes (so-called pleiotropy). For example, various genetic loci have been identified that seem to influence disease risk for psychiatric phenotypes but also inflammatory and other traits. In both areas of research (polygenicity and pleiotropy), our understanding of effects is almost exclusively limited to European ancestry populations. For example, our understanding of which genetic loci contribute to a child’s height is now almost saturated in Europeans. However, we still lack a similar degree of understanding for other ancestries. We hope to help reduce the resulting health diaspora through our research and focus on differences and similarities across populations in mechanisms that contributed to shaping the effect of genetic variation on human health and disease.
