Insight in Genome-Wide Association of Metabolite Quantitative Traits by Exome Sequence Analyses

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Human metabolic individuality is under strict control of genetic and environmental factors. In our study, we aimed to find the genetic determinants of circulating molecules in sera of large set of individuals representing the general population. First, we performed a hypothesis-free genome wide screen in this population to identify genetic regions of interest. Our study confirmed four known gene metabolite connections, but also pointed to four novel ones. Genome-wide screens enriched for common intergenic variants may miss causal genetic variations directly changing the protein sequence. To investigate this further, we zoomed into regions of interest and tested whether the association signals obtained in the first stage were direct, or whether they represent causal variations, which were not captured in the initial panel. These subsequent tests showed that protein coding and regulatory variations are involved in metabolite levels. For two genomic regions we also found that genes harbour more than one causal variant influencing metabolite levels independent of each other. We also observed strong connection between markers of cardio-metabolic health and metabolites. Taken together, our novel loci are of interest for further research to investigate the causal relation to for instance type 2 diabetes and cardiovascular disease.

Vyšlo v časopise: Insight in Genome-Wide Association of Metabolite Quantitative Traits by Exome Sequence Analyses. PLoS Genet 11(1): e32767. doi:10.1371/journal.pgen.1004835
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004835

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