Genetics is the study of heredity and inherited characteristics. It has the potential to revolutionise healthcare and dramatically reduce costs. Towards this end, scientists, through genomics research over the last two decades, have impressively populated genetic databases. The information in such databases, however, suffers from serious bias. Individuals of European descent are a mere 16 percent of the total world population, yet account for approximately 80 percent of all participants in genomic research. Despite the concurrence of scientists on the clinical significance of diversity in genomic research, progress in this regard has been unsatisfactory. To illustrate the global impact of this, I have analysed the subject from the perspective of the African population as this population constitutes less than 2 percent of human genomes studied.
Cystic Fibrosis (CF) is one of the most prevalent genetic disorders. Africans suffering from CF can have a life expectancy that is half as long as Europeans. Studies have shown that a significant reason for this is not only lack of population specific genetic tests in Africa, but also genetic variants of CF that are unique to this continent. Moreover, unlike developed countries, most African countries lack any national CF registration system, making it difficult to undertake genomic testing to identify variants that are unique to the African population. Underrepresentation of this population needs to be redressed as generalisations from studies done on European populations alone can lead to dangerous misdiagnosis of the disease.
Genomic research involving diverse populations boosts precision medicine, an innovative approach that tailors treatment according to an individual’s specific genes. 53 percent of people infected with human immunodeficiency virus (HIV) live in eastern and southern Africa. Efavirenz, an antiretroviral medication used to treat HIV infection globally, has an array of side effects. A variant called CYP2B6*6 is associated with severe side effects of Efavirenz and is carried by up to 47 percent of the African and African-American populations. Inclusive and targeted studies are necessary for the development of population-specific new drugs to treat HIV infection and reduce the side effects of drugs like Efavirenz.
Hypertrophic cardiomyopathy, a genetic cardiovascular disease, causes the thickening of the heart muscle. Even though pathogenic variants for this disease were found at a high frequency in the African American population, experts have warned that these variants are likely to have been misclassified as they are rare in white populations on whom genomic research is focused. Such misclassification has led to people of African ancestry receiving incorrect diagnosis, contributing to people of African ancestry receiving significantly poorer clinical care as compared to people of European ancestry.
Comprehensive genome-wide association studies are conducted to identify genetic variants and their traits. Fine mapping involves the determination of the genetic variants responsible for a complex trait (a trait that does not follow Mendelian patterns of inheritance). Through fine-mapping techniques, such as whole-genome sequencing, an association of genomic regions with a trait, such as height, can be predicted. Thus, the specific genetic variants within regions which are causally linked to the particular trait can be identified. By increasing diversity in genomics research, the resolution of fine mapping of these variants increases. More population-specific data obtained from fine-mapping could markedly improve the accuracy of prognosis and allow for better treatment of diseases.
The following conclusions can be drawn from the above examples: (a) study of genomics conducted on populations of European descent cannot be generalised to other populations; and (b) genomic research for more diverse populations will improve and boost clinical interventions, precision medicine, genetic diagnoses and fine-mapping resolution. Moreover, failure to investigate much more diverse samples of populations can significantly exacerbate the already appalling disparity in the quality of healthcare available to the rich and the poor.
Based on my study, a more regionally focused solution is required. For example, in a very recent development, the African Society of Human Genetics is starting a project called the ‘Three Million African Genomes’. Its endeavour is to sequence around three million African individuals to capture “the full scope of Africa’s genetic variation”. The global community must support this and similar regional initiatives as their potential to discover genes and variants not found in studies of European populations can dramatically improve healthcare for everyone on our planet.
For sources/citations please contact the writer at ammarkhaidermota@gmail.com.