Clinical impact of Population-specific genomic data

February 7, 2020 0 By FM

The demographic profile of the South Asian region is complex, with over 5,000 anthropologically defined groups. Figuring out how these groups differ from each other by studying their genetics can truly enable better healthcare. For example, anesthesiologists in South India will confirm with any patient who has to undergo surgery whether they belong to a community called Vysya. Vysyas are a small group in the South Indian states of Andhra Pradesh and Telangana, traditionally associated with trade and business. Medical practitioners know that this group of people can react adversely to muscle relaxants. Therefore, a different set of treatments is used for them. However, such information does not exist for a large number of other groups. It is therefore imperative that medical information has validation in several sub-populations in South Asia. It can be expected that many medical conditions have stayed genetically separate in spite of living side by side due to several cultural practices that are slowly changing in the urban areas. 

Human beings share 99.9% of the genome among themselves but it is the remaining 0.1% that makes a person unique. These changes are primarily represented by single nucleotide polymorphisms (SNPs). It is estimated that almost 85% of SNPs are common to all populations, but 15% are population-specific. These contribute to various characteristics, including susceptibility, predisposition, drug resistance, skin color and many more features. 

Some of the early reports (Xu et al, Blood Journal 1995) found that the incidence of G6PD deficiency varies among populations because of the proportion of SNP alleles similar to that of beta-thalassemia. Some recent studies have linked several SNPs responsible for disease susceptibility to physical features, but the majority of these studies were done in Caucasian countries and may not apply well to the Indian subcontinent, home to a quarter of the world’s population.

Value of genetic associations

Population-specific reference sequence and datasets will enable a deeper understanding and better clinical value, the primary goals of GenomeAsia study. The GenomeAsia project included large segments of the population which were not studied so far, and several characteristics including physical features, caste and others were sampled to understand the genetic associations.  

Several diseases which are highly prevalent in India have not been traced to their genetic levels yet. Genetic tests performed today use information generated from the Caucasian populations. The GenomeAsia project addresses this problem by including South Asia, Southeast Asia and Northeast Asia within its scope. These geographical regions contain many diverse populations and the information generated can give a clear understanding of founder SNPs or genetic variations for disease relevance. Within the diseases studied — including Maturity Onset Diabetes in the Young (MODY) and other highly prevalent diseases, important discoveries about candidate variants were found. The study also found some intergroup variations:For example, the HBB variant associated with beta-thalassemia is more frequent among South Asians compared to Southeast Asians. 

Effects of founder variants 

One of the most important tasks of population-based genome studies is to identify founder effects that have a greater association with diseases and can give a better understanding of how susceptible populations are to rare or complex diseases. This feature is called identical by descent (IBD) within and across the groups. When a population originates from a small group which has bred within, some genetic variations can get amplified among the members, compared to a large population where there is considerable gene flow. Many people carry founder variants and some of them could be disease associated mutations that may not show any effect if only one of the parents have it in their genes. In an endogamous group, they are more likely to express themselves in future generations due to common founder variant being passed on from both parents. The assessment of different groups for IBD scores revealed that urban groups scored higher than tribal groups. This also means that potential of homozygous loss-of-function genotypes among such groups, which can provide important insights into potential treatments. These genotypes often cause protein truncating variants (PTVs) that were not reported elsewhere. Several novel PTVs showed associations to diseases such as Alzheimer’s disease.  

GenomeAsia project has thrown light on several important findings and becomes one of the most important publications since the publication of human reference genome in 2001. Technological advancements have truly brought in changes to the way we can decypher personal human genomes at a very low cost. Now, clinical practices can imbibe the change positively to enhance patient care via personalized healthcare. This project further can help in laying a framework for the use of genetic information in healthcare and can potentially help governments in implementing guidelines for clinicians to practice.