@article {9376,
	title = {Whole-Genome Sequencing Analysis of Human Metabolome in Multi-Ethnic Populations.},
	journal = {Nat Commun},
	volume = {14},
	year = {2023},
	month = {2023 May 30},
	pages = {3111},
	abstract = {<p>Circulating metabolite levels may reflect the state of the human organism in health and disease, however, the genetic architecture of metabolites is not fully understood. We have performed a whole-genome sequencing association analysis of both common and rare variants in up to 11,840 multi-ethnic participants from five studies with up to 1666 circulating metabolites. We have discovered 1985 novel variant-metabolite associations, and validated 761 locus-metabolite associations reported previously. Seventy-nine novel variant-metabolite associations have been replicated, including three genetic loci located on the X chromosome that have demonstrated its involvement in metabolic regulation. Gene-based analysis have provided further support for seven metabolite-replicated loci pairs and their biologically plausible genes. Among those novel replicated variant-metabolite pairs, follow-up analyses have revealed that 26 metabolites have colocalized with 21 tissues, seven metabolite-disease outcome associations have been putatively causal, and 7 metabolites might be regulated by plasma protein levels. Our results have depicted the genetic contribution to circulating metabolite levels, providing additional insights into understanding human disease.</p>},
	keywords = {Ethnicity, Genome-Wide Association Study, Humans, Metabolome, Polymorphism, Single Nucleotide, Quantitative Trait Loci},
	issn = {2041-1723},
	doi = {10.1038/s41467-023-38800-2},
	author = {Feofanova, Elena V and Brown, Michael R and Alkis, Taryn and Manuel, Astrid M and Li, Xihao and Tahir, Usman A and Li, Zilin and Mendez, Kevin M and Kelly, Rachel S and Qi, Qibin and Chen, Han and Larson, Martin G and Lemaitre, Rozenn N and Morrison, Alanna C and Grieser, Charles and Wong, Kari E and Gersztern, Robert E and Zhao, Zhongming and Lasky-Su, Jessica and Yu, Bing}
}
