Genome-wide meta-analysis dissects the genetic basis and health implications of circulating taurine

Abstract

Taurine is a semiessential micronutrient critical to many biological processes. However, the genetic variation and the relationships between circulating taurine and human health are unclear. Here, we conducted the largest genome-wide meta-analysis to date, integrating summary statistics from five publicly available independent genome-wide association studies (GWAS) on circulating taurine levels in 36,490 European individuals. We employed LiftOver to harmonize genomic coordinates across the summary statistics derived from five large European cohorts with plasma taurine measurements, followed by a comprehensive genome-wide meta-analysis of both common and rare genetic variants. We utilized functional mapping and annotation and functional annotation of variants to identify genomic loci and variants and estimated global and local single-nucleotide polymorphism heritability using linkage disequilibrium score regression. In our study, we identified six common and two rare variant loci associated with circulating taurine and prioritized novel taurine-associated genes outside of the taurine transporter (SLC6A13) related to glutathione metabolism and neurotransmitter transport using an integrative pipeline. We used genetic proxies of circulating taurine to assess genetically supported putative causal associations on more than 17,000 clinical phenotypes via a phenome-wide Mendelian randomization analysis and demonstrated that genetically predicted circulating taurine shows evidence consistent with potential causal impacts on cancers, hypertension, neurodevelopment, abundance of Bifidobacterium, and brain phenotypes, among several others. We also identified genetic evidence consistent with modifiable relationships between circulating taurine and exposures, including bone mineral density, serum lactate, glycoproteins and creatinine. Collectively, this study systematically dissects the genetic basis of circulating taurine and highlights high-priority disease phenotypes requiring subsequent experimental validation for taurine-targeted nutritional and pharmacological strategies.