Genetic Determinants Influencing Human Serum Metabolome among African Americans

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Most contemporary GWAS studies have achieved increased power by increasing the size of the discovery sample to tens of thousands of individuals. An alternative approach for detecting the effects of novel loci is to measure phenotypes that more immediately reflect the effects of gene function. The metabolome consists of a collection of small molecules resulting from a variety of cellular and biologic processes, which can be considered intermediate phenotypes proximal to gene function. Here, we report a genome-wide association study identifying nineteen genetic loci influencing untargeted metabolomes traits among African Americans in the Atherosclerosis Risk in Communities (ARIC) Study. Fourteen genes mapped within nineteen loci, including twelve enzyme-encoding genes (KLKB1, SIAE, CPS1, NAT8, ACE, GATM, ACY3, ACSM2B, THEM4, ADH4, UGT1A and TREH), a transporter gene (SLC6A13) and a polycystin protein gene (PKD2L1). In addition, four potential disease-associated paths were identified, including two direct longitudinal predictive relationships: NAT8 with N-acetylornithine, N-acetyl-1-methylhistidine and incident chronic kidney disease, and TREH with trehalose and incident diabetes. These results highlight the value of using phenotypes proximal to gene function to promote novel gene discovery.

Vyšlo v časopise: Genetic Determinants Influencing Human Serum Metabolome among African Americans. PLoS Genet 10(3): e32767. doi:10.1371/journal.pgen.1004212
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004212

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