A Map of Multi-omics Quantitative Trait Loci in a Chinese Population Reveals Regulatory Variations and Disease Links

Quantitative trait loci (QTL) studies have been pivotal in mapping the genetic regulation of molecular traits but have been primarily conducted in European populations, limiting insights into diverse ethnic groups. To close this knowledge gap, we conducted a large-scale multi-omics QTL analyses using blood samples from 3,102 Chinese individuals, systematically characterizing the regulatory effects of genetic variants on DNA methylation, protein levels, and metabolites. Our study identified 209 protein QTLs (pQTLs) for 155 proteins and 587 metabolite QTLs (metabQTLs) for 369 metabolites. By integrating these findings with cis-methylation QTL (meQTL) associations identified in our previous work, we defined the shared genetic architecture across these three molecular layers. Colocalization analyses, both within our cohort and with external xQTLs, revealed 3,665 pairs of shared causal variants across traits, supported by strong mediation evidence for a regulatory cascade in 187 pairs. To link these molecular findings to health outcomes, we performed Mendelian randomization (MR) analyses, identifying 497 potential causal relationships between molecular traits and diseases. These findings were further validated through observational and colocalization studies. Collectively, we present a comprehensive genomic atlas of meQTLs, pQTLs, and metabQTLs specific to East Asian populations, providing critical insight into shared regulatory networks and candidate causal variants across molecular and disease phenotypes.