![]() ![]() Through activation of these diverse signalling pathways, BAs control not only their own transport and metabolism, but also lipid and glucose metabolism, and innate and adaptive immunity 3. Bile acids also act as hormone-like signalling molecules, serving as ligands to nuclear (hormone) receptors. Once secreted in the lower gastrointestinal tract, primary BAs are heavily modified by the gut microbiota to produce a broad range of secondary BAs, with deoxycholic acid (DCA), a CA derivative, and lithocholic acid (LCA), a CDCA derivative, being the most prevalent 2. Primary bile acids in humans consists of cholic acid (CA), chenodeoxycholic acid (CDCA), and their taurine- or glycine-bound derivatives (TCA and TCDCA, GCA and GCDCA). Approximately 95% of BAs are then re-absorbed by the intestinal epithelium and transported back to the liver via the portal vein - a process termed “enterohepatic circulation” 2. After ingestion of food, BAs are secreted into the small intestine, where they contribute to the digestion of lipid-soluble nutrients 1. Using gene-based aggregate tests and whole exome sequencing, we identify rare pLoF and missense variants potentially associated with bile acid levels in 3 genes ( OR1G1, SART1 and SORCS2), some of which have been linked with liver diseases.īile acids (BAs) are synthesised from cholesterol in the liver and subsequently stored in the gallbladder. By performing genome-wide association analysis (GWAS) of plasma blood levels of 18 bile acids (N = 4923) we identify two significantly associated loci, a common variant mapping to SLCO1B1 (encoding a liver bilirubin and drug transporter) and a rare variant in PRKG1 (encoding soluble cyclic GMP-dependent protein kinase). Here we investigate the genetic architecture of primary and secondary bile acids in blood plasma, reporting associations with both common and rare variants. While many studies have focused on the genetic determinants of blood metabolites, research focusing specifically on genetic regulation of bile acids in the general population is currently lacking. Bile acids are essential for food digestion and nutrient absorption, but also act as signalling molecules involved in hepatobiliary diseases, gastrointestinal disorders and carcinogenesis. ![]()
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