In this study, a total of 47,532 East Asian participants were recruited from Hong Kong, China, Taiwan and Singapore. Using the custom designed Exome-chip, the research teams discovered novel associations between blood lipid levels with DNA variations in three novel genes (ACVR1C, MCU and CD163) that have not been previously reported,
and also 14 East Asian-specific protein-altering variants in 11 known genes. Further integration of the Exome-chip data with over 300,000 individuals, primarily of European ancestry, recruited by the international GLGC, revealed an additional nine novel variants associated with blood lipids across populations. Examination of these lipid-associated variants in 28,889 Chinese individuals with and without CAD together with ~185,000 CAD cases and controls from the CADIoGRAMplusC4D consortium highlighted strong correlation between their effects on LDL cholesterol level and CAD risk, which includes the newly identified LDL-lowering MCU variants that offers protection against CAD. These groundbreaking findings will help assess the risk of CAD in our Asian population and elucidate the underlying disease mechanisms. Overall, the new findings demonstrated that rare protein-altering variants are generally of larger effects and are likely to be population specific, which underscores the significance of discovering ancestry-specific lipid-associated variants in East Asians using Exome-chip.
Precision medicine is an emerging approach for improved medical care whereby diagnosis, treatment and prevention of diseases are customised according to the individual person’s genetic profile to promote good health. While existing panels for genetic risk prediction rely on discoveries from the Europeans, the findings published in this paper provide a new reference panel most relevant to the Asian population for risk prediction of abnormal blood lipid levels and CAD. This new panel can further facilitate the development of risk prediction array to inform clinicians on the high-risk group of individuals that require earlier monitoring or intervention. Moreover, the new knowledge also provides novel insights into the biology of lipid metabolism which can be translated to the discovery and development of new drugs for preventing heart disease through lowering blood lipids.