New analysis of genetic diversity within the British Pakistani population will have important implications for medical studies, according to researchers.
The study - the first of its kind - reveals that the genetic structure of this population has been shaped over a period of about 2,000 years by the biraderi social system - a practice of marrying within clans.
The fine-scale analysis details genetic differences between biraderi groups that will have important implications for the design of medical studies seeking to discover the genetic roots of common illnesses such as diabetes and heart disease.
The data will help to ensure those of Pakistani ancestry are represented in such research and will be able to benefit from new knowledge and therapies that emerge.
He said: “The study represents a step forward in the potential benefits of genetic research for marginalised populations, consistent with a wish to broaden the knowledge base and clinical benefits of genetic studies.”
Human genomes - the complete set of genetic information - are approximately 99.9% identical in each person, regardless of ancestry.
The remaining 0.1% holds differences between individuals, called genetic variants, which make us unique.
Most genetic research to date has been conducted on European-ancestry individuals, which has led to a fuller understanding of human genetic variation, population structure and the role of genetic variation in disease.
However, findings about the genetic contribution to disease in Europeans may not translate well to individuals of other ethnicities.
In recent years, studies of non-Europeans have started to provide a more complete picture of human genetic diversity and associated medical implications.
History and culture have influenced the genetic make-up of populations from different parts of the world. One such cultural factor is the biraderi social system, which has been practised in Pakistani populations for centuries.
Historically, people tended to marry within their own biraderi (community) to reinforce hereditary social status, occupation and land ownership.
This system is still practised to some extent today, both in Pakistan and within Pakistani-ancestry populations in countries like the UK.
In this study, researchers analysed genomes from over 4,000 Pakistani-ancestry individuals, together with self-reported information about their family history*, to investigate the genetic characteristics of the British Pakistani population.
These data were collected by the Bradford Institute for Health Research (BIHR) as part of the Born in Bradford project**.
Scientists at Leeds and the Wellcome Sanger Institute analysed the genomic data to map the fine-scale population structure and explore the demographic history of British Pakistanis.
Though Bradford Pakistani groups were found to be genetically similar to other Pakistani and Indian populations, the study found evidence that the biraderi social system has played an important role in shaping genetic variation.
Participants shared the same genetic history until around 2,000 years ago, when they started separating into biraderi groups, including the Pathan, Jatt, Rajput, Awan, Gujjar, Mughal, Syed, Arain, Qasabi, and Bains.
Sanger’s Dr Elena Arciero conducted analysis that revealed that some groups experienced reductions in effective population size at various points in history***. This could have been due to an increase in marriage-within-groups or an actual reduction in the population size as recorded in census data.
Dr Sufyan Dogra, Senior Research Fellow from the Bradford Institute for Health Research (BIHR), said: “Prior to this study, our knowledge of the genetic history of these biraderis was quite sparse, so it adds considerably to our understanding of the social history of Pakistan.
“There is historical evidence to suggest that marriage within biraderi groups began to increase around 2,000 years ago and became stricter during colonial times under the British Raj, when new property taxes were introduced to generate revenue.
“This may explain the reduction in effective population size that we observe in the genomic data.”
Previous research from Born in Bradford has shown that there is an increase in risk of recessive disorders amongst the children of first cousins, which is similar to that for children born to white British mothers aged 34 and over****.
This study finds that recessive disorders are likely to be more common amongst the children of couples who are not closely related but come from the same biraderi group, because their parents are distantly related.
However, the risk is at least ten times higher for children of first cousins than for children of unrelated parents from the same biraderi.
The findings have important medical implications for British Pakistanis. Incidence of common diseases like type-2 diabetes and heart disease are two-to-four times higher than in the white British population.
The detailed genetic structure mapped in the study will help researchers to design future studies and search for common variants associated with these and other health problems, with the aim of improving diagnosis and treatment of these diseases as well as tailoring preventative advice.
Dr Hilary Martin, a senior author of the study from the Wellcome Sanger Institute, said: “It is important to understand the fine-scale structure of a population when planning medical research such as genome-wide association studies.
“I hope our findings will provide a foundation for future research into the causes of genetic disease in Pakistani populations.”
*Participants were asked to report their biraderi group, whether their parents were related, and the place they or their parents originate from in Pakistan.
**These data were collected by researchers at the University of Bradford, the University of Leeds and the Bradford Institute of Health Research (BIHR) for the Born in Bradford study, which is investigating the environmental, social and genetic causes of poor health and life outcomes in one of the most deprived cities in the UK, using data from over 10,000 families. Professor Neil Small, an author of this study from the University of Bradford, said: “The Born in Bradford study has been underway since 2007 and has had considerable input into ways health and wellbeing can be improved in the city. The Born in Bradford team seeks the advice of study participants and shares findings in publications and meetings that local people can access. Advice was taken in this particular research from members of the Bradford Pakistani community who were recognised as having particular interest and expertise in how that community is organised.”
***Effective population size reflects the proportion of people in the population who are having children and their marriage patterns, rather than the true (census) population size. For example, if a country has a total population size of one million people, but, for generations everyone chooses their partner from the 500 individuals who live in their village, the effective population size will be much smaller than one million.
****Recessive disorders are those in which a child has to inherit a particular DNA variant from both parents to be affected. Earlier research has shown higher levels of risk in marriages where parents were related by blood. More information on the comparative risk.
“Fine-scale population structure and demographic history of British Pakistanis” by Elena Arciero et al (2021) is published in Nature Communications.
Funding: this work was supported by Wellcome.