Validation of a genome-wide polygenic score for coronary artery disease in South Asians Academic Article uri icon

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

authors

  • Wang, M
  • Menon, R
  • Mishra, S
  • Patel, AP
  • Chaffin, M
  • Tanneeru, D
  • Deshmukh, M
  • Mathew, O
  • Apte, S
  • Devanboo, CS
  • Sundaram, S
  • Lakshmipathy, P
  • Murugan, S
  • Sharma, KK
  • Rajendran, K
  • Santhosh, S
  • Thachathodiyl, R
  • Ahamed, H
  • Balegadde, AV
  • Alexander, T
  • Swaminathan, K
  • Gupta, R
  • Mullasari, AS
  • Sigamani, A
  • Kanchi, M
  • Peterson, AS
  • Butterworth, AS
  • Danesh, J
  • Di Angelantonio, E
  • Naheed, A
  • Inouye, Michael
  • Chowdhury, R
  • Vedam, RL
  • Kathiresan, S
  • Gupta, R
  • Khera, AV

publication date

  • 2020