Rare and Common Genetic Determinants of Metabolic Individuality and Their Effects on Human Health

The study examined the genetic architecture of over 900 metabolites in nearly 20,000 individuals to understand the genetic regulation of biochemical individuality. The researchers identified 1,847 associations of 330 genomic regions with 646 metabolites and found 423 genetically influenced metabotypes (GIMs). They discovered that variation near the SRD5A2 gene, associated with male-pattern baldness, was linked with eight steroid metabolites. Two genetic variants near the SRD5A2 gene were found to alter steroid metabolism, with one variant associated with a lower risk for male-pattern baldness and another linked to an increased risk for depression. The study also identified four variants in the DPYD region, which is involved in the breakdown of certain cancer chemotherapies, and these variants were associated with higher plasma uracil levels, suggesting a potential risk of treatment-induced toxicity. The study concluded that genetic variations significantly influence metabolic individuality and have diverse health implications.