| Title: | Validation of a Genome-Wide Polygenic Score for Coronary Artery Disease in South Asians |
| Journal: | Journal of the American College of Cardiology |
| Published: | 1 Aug 2020 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/32762905/ |
| DOI: | https://doi.org/10.1016/j.jacc.2020.06.024 |
Publication 5975
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Abstract
BACKGROUND: Genome-wide polygenic scores (GPS) integrate information from many common DNA variants into a single number. Because rates of coronary artery disease (CAD) are substantially higher among South Asians, a GPS to identify high-risk individuals may be particularly useful in this population.</p>
OBJECTIVES: This analysis used summary statistics from a prior genome-wide association study to derive a new GPSCAD for South Asians.</p>
METHODS: This GPSCAD was validated in 7,244 South Asian UK Biobank participants and tested in 491 individuals from a case-control study in Bangladesh. Next, a static ancestry and GPSCAD reference distribution was built using whole-genome sequencing from 1,522 Indian individuals, and a framework was tested for projecting individuals onto this static ancestry and GPSCAD reference distribution using 1,800 CAD cases and 1,163 control subjects newly recruited in India.</p>
RESULTS: The GPSCAD, containing 6,630,150 common DNA variants, had an odds ratio (OR) per SD of 1.58 in South Asian UK Biobank participants and 1.60 in the Bangladeshi study (p < 0.001 for each). Next, individuals of the Indian case-control study were projected onto static reference distributions, observing an OR/SD of 1.66 (p < 0.001). Compared with the middle quintile, risk for CAD was most pronounced for those in the top 5% of the GPSCAD distribution-ORs of 4.16, 2.46, and 3.22 in the South Asian UK Biobank, Bangladeshi, and Indian studies, respectively (p < 0.05 for each).</p>
CONCLUSIONS: The new GPSCAD has been developed and tested using 3 distinct South Asian studies, and provides a generalizable framework for ancestry-specific GPS assessment.</p>
12 Keywords
- Adult
- Aged
- Bangladesh
- Case-Control Studies
- Coronary Artery Disease
- Female
- Genome-Wide Association Study
- Humans
- India
- Male
- Middle Aged
- Multifactorial Inheritance
36 Authors
- Minxian Wang
- Ramesh Menon
- Sanghamitra Mishra
- Aniruddh P. Patel
- Mark Chaffin
- Deepak Tanneeru
- Manjari Deshmukh
- Oshin Mathew
- Sanika Apte
- Christina S. Devanboo
- Sumathi Sundaram
- Praveena Lakshmipathy
- Sakthivel Murugan
- Krishna Kumar Sharma
- Karthikeyan Rajendran
- Sam Santhosh
- Rajesh Thachathodiyl
- Hisham Ahamed
- Aniketh Vijay Balegadde
- Thomas Alexander
- Krishnan Swaminathan
- Rajeev Gupta
- Ajit S. Mullasari
- Alben Sigamani
- Muralidhar Kanchi
- Andrew S. Peterson
- Adam S. Butterworth
- John Danesh
- Emanuele Di Angelantonio
- Aliya Naheed
- Michael Inouye
- Rajiv Chowdhury
- Ramprasad L. Vedam
- Sekar Kathiresan
- Ravi Gupta
- Amit V. Khera
Enabling scientific discoveries that improve human health