South Asian Patient Population Genetics Reveal Strong Founder Effects and High Rates of Homozygosity – New Resources for Precision Medicine
| Autor: | Saurabh Belsare, Sameer Phalke, Anamitra Barik, Deepak Tanneeru, Naveen Kumar Naik, Pui-Yan Kwok, Ravi Gupta, Christian Fuchsberger, Adam S. Butterworth, Jacqueline Robinson, Sebastian Schoenherr, Arkasubhra Ghosh, Virinder Mohan, Lukas Forer, Amit Khera, Qixin Bei, Jeffrey D. Wall, J. Fah Sathirapongsasuti, Sekar Seshagiri, B. V. Priya, Anuradha Mittal, B. R. Lakshmi, Rajesh Kumar Rai, Jennifer Tom, Ramesh Menon, Sekar Kathiresan, Tushar Bhangale, Abhijit Chowdhury, Asif Rasheed, Santosh Gopi Krishna Gadde, John Fang, Ruchi Chaudhary, Venkatesan Radha, Andrew S. Peterson, Eric Stawiski, Minxian Wang, John Danesh, Danish Saleheen |
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| Rok vydání: | 2020 |
| Předmět: |
Genetics
0303 health sciences education.field_of_study Population Consanguinity Disease 3. Good health 03 medical and health sciences 0302 clinical medicine Geography Endogamy Genetic variation education Genotyping 030217 neurology & neurosurgery 030304 developmental biology Founder effect SNP array |
| DOI: | 10.1101/2020.10.02.323238 |
| Popis: | Population-scale genetic studies can identify drug targets and allow disease risk to be predicted with resulting benefit for management of individual health risks and system-wide allocation of health care delivery resources. Although population-scale projects are underway in many parts of the world, genetic variation between population groups means that additional projects are warranted. South Asia has a population whose genetics is the least characterized of any of the world’s major populations. Here we describe GenomeAsia studies that characterize population structure in South Asia and that create tools for economical and accurate genotyping at population-scale. Prior work on population structure characterized isolated population groups, the relevance of which to large-scale studies of disease genetics is unclear. For our studies we used whole genome sequence information from 4,807 individuals recruited in the health care delivery systems of Pakistan, India and Bangladesh to ensure relevance to population-scale studies of disease genetics. We combined this with WGS data from 927 individuals from isolated South Asian population groups, and developed a custom SNP array (called SARGAM) that is optimized for future human genetic studies in South Asia. We find evidence for high rates of reproductive isolation, endogamy and consanguinity that vary across the subcontinent and that lead to levels of homozygosity that approach 100 times that seen in outbred populations. We describe founder effects that increase the power to associate functional variants with disease processes and that make South Asia a uniquely powerful place for population-scale genetic studies. |
| Databáze: | OpenAIRE |
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