Being Precise: Genomic Medicine
From treatment and management of chronic ailments, cancers and lifestyle disorders to drug and vaccine development, surveillance, diagnostics and preventive care, genomics is penetrating every aspect of life. The present pandemic has brought genomics to the forefront in the areas of viral surveillance, tracking and real-time decision making. With different world populations having their unique genetic make-up, population level genomics is likely to gain relevance in designing region specific healthcare policies and charting out appropriate programmes.
Genomics in individual and community health
Genomic profiling has already shown great value in risk prediction for Huntington’s disease, hereditary form of cancers and metabolic diseases in which the body is unable to break down certain types of dietary compounds. The treatment of these potentially fatal conditions is invasive, expensive and prone to severe side effects, thus making the genetic prediction of crucial importance. Such conditions are determined by a single gene (monogene) and its cause-effect relationship is easy to decipher.
Disease management of conditions such as diabetes, which affects 1 in 11 individuals worldwide, is gaining priority. Predicting multi-gene disorders such as diabetes and coronary heart disease (CHD) can be difficult using a genetic approach since they are determined by the cumulative effect of many genes and also environmental factors. Adding to the complexity are co-occurring diseases where the occurrence of one makes an individual susceptible to another disease.
Diabetes, for example, is associated with various general and organ specific complications, of which CHD is the most prominent. Susceptibility associated gene variants having high predictive value, either for occurrence of individual condition or co-occurrence with another, may show a low overall predictive value when taken together with other similar gene variants in other parts of the person’s DNA; thereby showing only a marginal increase or decrease in comparison to the average risk factor of the entire community.
Multi-country studies have shown a genetic association between diabetes and risk for CHD; in many cases it also reports exceptions that are difficult to explain. All of these genetic variations carry a nominal risk factor and it is now more or less clear that diabetes and other lifestyle diseases are not overtly genetics-based; rather, they are manifestations of modifications in the genome. At present all the discovered DNA variations together cannot explain more than 10 per cent of the risks.
Previous studies have shown that new yet unknown gene pathways and novel intermediate biomarkers may be stronger predictors of disease than the genetic variant that led to its identification. These new discoveries will additionally help in a better understanding of the disease and motivate researchers to think of alternate risk factors.
On the one hand, an increasing number of studies are reporting gene variants, which potentially predict disease progression in different clinical settings, both for monogenic and multi-gene disorders. On the other hand, many researchers believe that identifying combinations of causal gene variants with high disease predictive values, even within the same population is unlikely for complex multigene diseases such as diabetes and CHD. This may be true even though the variants by themselves may be common as the combinations are likely to be rare. Effects of gene-gene and gene-environment interaction along with ethnic differences within populations are the other factors to be considered.
Genomics of cancers is another widely studied area. Identification of genes associated with different types of cancer and the presence of their high-risk variants has been identified here as well. Another aspect of genomics that is studied extensively in cancers is epigenomics or the DNA modification pattern with different chemical moieties.
[Next: Genomics to the rescue!]
The article is second of three parts of a larger article published in the September-October 2021 issue of Invention Intelligence, a magazine published by the National Research Development Corporation (NRDC), A DSIR Enterprise, Ministry of Science & Technology, Government of India.
Also read Part-1 (Race to the Genomes)and Part-3 (Genomics to the rescue!)
