Details

Autor(en) / Beteiligte

• 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

Titel

Validation of a Genome-Wide Polygenic Score for Coronary Artery Disease in South Asians

Ist Teil von

• Journal of the American College of Cardiology, 2020-08, Vol.76 (6), p.703-714

Ort / Verlag

United States

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.