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Whole-Genome Sequencing Analysis of Human Metabolome in Multi-Ethnic Populations.
Thursday,2023-06-15 16:59 America/Los_Angeles — ecterry
| Title | Whole-Genome Sequencing Analysis of Human Metabolome in Multi-Ethnic Populations. |
| Publication Type | Journal Article |
| Year of Publication | 2023 |
| Authors | Feofanova, EV, Brown, MR, Alkis, T, Manuel, AM, Li, X, Tahir, UA, Li, Z, Mendez, KM, Kelly, RS, Qi, Q, Chen, H, Larson, MG, Lemaitre, RN, Morrison, AC, Grieser, C, Wong, KE, Gersztern, RE, Zhao, Z, Lasky-Su, J, Yu, B |
| Corporate/Institutional Authors | NHLBI Trans-Omics for Precision Medicine (TOPMed) |
| Journal | Nat Commun |
| Volume | 14 |
| Issue | 1 |
| Pagination | 3111 |
| Date Published | 2023 May 30 |
| ISSN | 2041-1723 |
| Keywords | Ethnicity, Genome-Wide Association Study, Humans, Metabolome, Polymorphism, Single Nucleotide, Quantitative Trait Loci |
| 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> |
| DOI | 10.1038/s41467-023-38800-2 |
| Alternate Journal | Nat Commun |
| PubMed ID | 37253714 |
| PubMed Central ID | PMC10229598 |
| Grant List | R01 HL168683 / HL / NHLBI NIH HHS / United States R01 HL120393 / HL / NHLBI NIH HHS / United States K08 HL161445 / HL / NHLBI NIH HHS / United States HHSN268201500014C / HL / NHLBI NIH HHS / United States R01 HL136574 / HL / NHLBI NIH HHS / United States U54 HG003067 / HG / NHGRI NIH HHS / United States U54 HG003273 / HG / NHGRI NIH HHS / United States R01 HL092577 / HL / NHLBI NIH HHS / United States R01 HL131136 / HL / NHLBI NIH HHS / United States HHSN268201100037C / HL / NHLBI NIH HHS / United States HHSN268201500015C / HL / NHLBI NIH HHS / United States R01 HL117626 / HL / NHLBI NIH HHS / United States R01 HL141824 / HL / NHLBI NIH HHS / United States HHSN268201600031C / HL / NHLBI NIH HHS / United States HHSN268201000001I / HL / NHLBI NIH HHS / United States R01 HL142003 / HL / NHLBI NIH HHS / United States R01 LM012806 / LM / NLM NIH HHS / United States T15 LM007093 / LM / NLM NIH HHS / United States |
ePub date:
23/05