Y. Ko

TL;DR: Circulating SAA levels but not SAA1 genetic variants could predict long-term outcomes in patients with angiographically confirmed CAD, but notSAA1 genotypes contributed significantly to SAA Levels in the general population and in patientsWith CAD.

TL;DR: The findings reveal that the E670G G allele is independently associated with a decreased likelihood of developing elevated Lp(a) levels, and this association persists even after adjusting for common cardiovascular risk factors and irrespective of lipid profile variations.

Abstract: ABSTRACT Background Physical inactivity contributes to systemic disease burden and premature mortality worldwide. Leisure-time physical activity (LTPA) improves health outcomes; however, its genetic determinants, particularly in Asian populations, remain unclear. This study aimed to identify genetic loci associated with LTPA in the Taiwanese population. Methods We conducted genome-wide association studies in 122,258 Taiwan Biobank participants. LTPA was assessed both as a binary trait (regular exerciser vs non-exerciser) and an ordinal trait (categorized by MET-hours per week into low, moderate, and high physical activity levels). Logistic and ordinal logistic regression models were used under an additive genetic model, adjusting for age, age2, sex, body mass index, smoking, and the first 10 genetic principal components. Candidate nonsynonymous mutations were further examined in 1494 whole-genome sequenced participants. Results Binary trait genome-wide association studies identified genome-wide significant (GWS) loci at ATXN2 (12q24.12), FTO (16q12.2), and NOTCH4 (6p21.32), with associations for FTO and NOTCH4 only observed in body mass index (BMI)–adjusted models. Ordinal trait analysis (<10, 10–<20, ≥20 MET·h·wk−1) identified a single GWS locus at BRAP (12q24.12). Fine-mapping of 12q24.12 revealed multiple GWS single-nucleotide polymorphisms (SNPs) in strong linkage disequilibrium with lead variants; these signals largely disappeared after conditional analysis, consistent with a single underlying association. Whole-genome sequencing and linkage disequilibrium analysis identified three GWS nonsynonymous mutations, with ALDH2 rs671 emerging as the most likely causal variant. Conclusions ATXN2–ALDH2 region on chromosome 12q24.12 was identified as a key locus for LTPA in Taiwanese individuals. These findings enhance our understanding of the genetic basis of physical activity and may inform future precision medicine and public health strategies.

TL;DR: The findings highlight genetic variants around the α-globin genes as surrogate markers for common α-thalassemia mutations in Taiwan, emphasizing the causal links between α-thalassemia-related erythrocyte indices, cardiometabolic traits, and heightened diabetes risk.