Differential Effects of Gene Region Variants on Lipid Profile, Blood Pressure Status, and Gallstone Disease History in Taiwan.

ABCG5 and ABCG8 are two key adenosine triphosphate-binding cassette (ABC) proteins that regulate whole-body sterol trafficking. This study aimed to elucidate the association between gene region variants and lipid profile, cardiometabolic traits, and gallstone disease history in Taiwan. A total of 1494 Taiwan Biobank participants with whole-genome sequencing data and 117,679 participants with Axiom Genome-Wide CHB Array data were enrolled for analysis. Using genotype-phenotype and stepwise linear regression analyses, we found independent associations of four Asian-specific variants, rs119480069, rs199984328, rs560839317, and rs748096191, with total, low-density lipoprotein (LDL), and non-high-density lipoprotein (HDL) cholesterol levels (all ≤ 0.0002). Four other variants, which were in nearly complete linkage disequilibrium, exhibited genome-wide significant associations with gallstone disease history, and the rs11887534 variant showed a trend of superiority for gallstone disease history in a nested logistic regression model ( = 0.074). Through regional association analysis of various other cardiometabolic traits, two variants of the , approximately 50 kb from the region, exhibited significant associations with blood pressure status ( < 10). In conclusion, differential effects of region variants were noted for lipid profile, blood pressure status, and gallstone disease history in Taiwan. These results indicate the crucial role of individualized assessment of variants for different cardiometabolic phenotypes.