GWAS META-analysis followed by MENDELIAN randomisation revealed potential control mechanisms for circulating α-klotho levels.
Ingrid GergeiYufang BiTill F M AndlauerVincent BrandenburgNazanin Mirza-SchreiberBertram Müller-MyhsokBernhard K KrämerDaniel RichardLouise FalkSofia Movérare-SkrticClaes OhlssonGeorge Davey SmithWinfried MärzJakob VoelklJonathan H TobiasPublished in: Human molecular genetics (2021)
Our GWAS findings suggest that two enzymes involved in post-translational modification, B4GALNT3 and CHST9, contribute to genetic influences on α-Klotho levels, presumably by affecting protein turnover and stability. Subsequent evidence from MR analyses on α-Klotho levels suggest regulation by mechanisms besides phosphate-homeostasis and raise the possibility of cross-talk with FGF19- and FGF21-dependent pathways, respectively.