Genetics & South Asian Populations

The picture shows people from the 1000 Genomes Project. Genomics is big data, and big data is usually not random. It is more organised and has a structure. We have used a maths technique called PCA to find the structure corresponding to people's ethnic origin.

In this article, we will discuss the genetic make-up of South Asian populations, and why the study is looking at British Asians in East London.

Why focus on Bangladeshi and Pakistani people in East London?

At present, the study is recruiting only adult volunteers from across East London who regard themselves of Bangladeshi, British-Bangladeshi, Pakistani or British-Pakistani origin. There are several reasons for this:

Some of the most health deprived people in the UK are in East London, on the doorstep of our NHS hospital, primary care and medical school/university facilities.
For example, Bangladeshi and Pakistani people in the UK have five times the rates of diabetes, and poor health by many other measures.
Bangladeshi and Pakistani people are the largest ethnic minority groups in East London.
We know the genetic make-up of South Asians differs, for example differences between Bangladeshi, Pakistani, and Tamil people can easily be seen at the genome level.
We can see fit adults with knockout genes more commonly where there is parental relatedness.
We have excellent and joined-up primary care NHS electronic health records on over a million people in East London. This will enable us to compare genetics and health conditions at a large scale, which is harder to do in other parts of the UK and other countries.
Many health research and genetic studies have focused more on other populations (for example, white European origin people). South Asian people are understudied, and so to enable local people to benefit from the coming genomics revolution in healthcare we have set up East London Genes & Health.

What can you tell about the genetic make-up of South Asians?

Genetic admixture analysis - colours show main ancestral groups, with modern day groups on the left. [Rosenberg 2007]

In typical current human genetic studies, people’s DNA is sequenced at all protein-coding genes (the “exome”) or in entirety (the “whole genome”), or directly tested (“genotyped”) at >100,000 individual positions in the sequence that are known to vary between people. This provides a large set of data. The pattern of genetic variants seen in an individual is not random, rather it is quite organized and has structure. For example variants close together in the genome tend to be inherited together in one block.

Although most humans are the same for 99% of their DNA sequence, the small part that differs can tell us a lot. The pattern of genetic variation that we see depends on the genetic make-up of your parents. We know the genetic make-up of South Asians differs, for example differences between Bangladeshi, Pakistani, and Tamil people can easily be seen at the genome level. By studying how your genetic make-up is shared between groups it is possible to identify the proportion of your ancestry that is associated with different ethnic groups. Genetic studies from the past have shown that almost all modern day South Asians, even those from the most isolated tribal groups, descend from two ancestral human populations. These two populations met in the distant past and each individual has a varying amount of each component. After this period of widespread mixture, the practice of marrying within specific ethnic and social groups arose around some 2000 years ago and mixing between groups became very rare.

Some of these population specific differences can contribute to human diseases. For example, a small percentage of South Asian people carry a genetic variant in a gene called MYBPC3 that increases the risk of heart failure and heart attacks in later life. This variant was thought to have arisen around 30,000 years ago.

Genetic variation that occurs rarely, for example only seen in one or a few of thousands of people, usually is specific to particular ethnic groups. This is because these changes are usually fairly recent (the variant happened in recent generations) in human history, and your immediate ancestors will not have moved around much.

In genetic studies, it is important to identify clearly defined ethnic groups, otherwise when comparing between conditions (for example people with and without diabetes) any differences seen might be due to differences in ethnicity rather than the condition being studied. East London Genes & Health is initially studying people only of Bangladeshi and Pakistani heritage.