%0 Journal Article %J J Am Coll Cardiol %D 2020 %T Validation of a Genome-Wide Polygenic Score for Coronary Artery Disease in South Asians. %A Wang, Minxian %A Menon, Ramesh %A Mishra, Sanghamitra %A Patel, Aniruddh P %A Chaffin, Mark %A Tanneeru, Deepak %A Deshmukh, Manjari %A Mathew, Oshin %A Apte, Sanika %A Devanboo, Christina S %A Sundaram, Sumathi %A Lakshmipathy, Praveena %A Murugan, Sakthivel %A Sharma, Krishna Kumar %A Rajendran, Karthikeyan %A Santhosh, Sam %A Thachathodiyl, Rajesh %A Ahamed, Hisham %A Balegadde, Aniketh Vijay %A Alexander, Thomas %A Swaminathan, Krishnan %A Gupta, Rajeev %A Mullasari, Ajit S %A Sigamani, Alben %A Kanchi, Muralidhar %A Peterson, Andrew S %A Butterworth, Adam S %A Danesh, John %A Di Angelantonio, Emanuele %A Naheed, Aliya %A Inouye, Michael %A Chowdhury, Rajiv %A Vedam, Ramprasad L %A Kathiresan, Sekar %A Gupta, Ravi %A Khera, Amit V %K Adult %K Aged %K Bangladesh %K Case-Control Studies %K Coronary Artery Disease %K Female %K Genome-Wide Association Study %K Humans %K India %K Male %K Middle Aged %K Multifactorial Inheritance %X

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.

OBJECTIVES: This analysis used summary statistics from a prior genome-wide association study to derive a new GPS for South Asians.

METHODS: 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.

RESULTS: 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).

CONCLUSIONS: The new GPS has been developed and tested using 3 distinct South Asian studies, and provides a generalizable framework for ancestry-specific GPS assessment.

%B J Am Coll Cardiol %V 76 %P 703-714 %8 2020 08 11 %G eng %N 6 %1 https://www.ncbi.nlm.nih.gov/pubmed/32762905?dopt=Abstract %R 10.1016/j.jacc.2020.06.024