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Wang, Minxian; Menon, Ramesh; Mishra, Sanghamitra; Patel, Aniruddh P; Chaffin, Mark; Tanneeru, Deepak; Deshmukh, Manjari; Mathew, Oshin; Apte, Sanika; Devanboo, Christina S; Sundaram, Sumathi; Lakshmipathy, Praveena; Murugan, Sakthivel; Sharma, Krishna Kumar; Rajendran, Karthikeyan; Santhosh, Sam; Thachathodiyl, Rajesh; Ahamed, Hisham; Balegadde, Aniketh Vijay; Alexander, Thomas; Swaminathan, Krishnan; Gupta, Rajeev; Mullasari, Ajit S; Sigamani, Alben; Kanchi, Muralidhar; Peterson, Andrew S; Butterworth, Adam S; Danesh, John; Di Angelantonio, Emanuele; Naheed, Aliya; Inouye, Michael; Chowdhury, Rajiv; Vedam, Ramprasad L; Kathiresan, Sekar; Gupta, Ravi; Khera, Amit V
Journal of the American College of Cardiology, 08/2020, Letnik: 76, Številka: 6Journal Article
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. This analysis used summary statistics from a prior genome-wide association study to derive a new GPS for South Asians. This GPS 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 GPS 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 GPS reference distribution using 1,800 CAD cases and 1,163 control subjects newly recruited in India. The GPS , 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 GPS 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). The new GPS has been developed and tested using 3 distinct South Asian studies, and provides a generalizable framework for ancestry-specific GPS assessment.
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in: SICRIS
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