Ancestry-driven metabolite variation provides insights into disease states in admixed populations

Genome Med. 2023 Jul 17;15(1):52. doi: 10.1186/s13073-023-01209-z.


Background: Metabolic pathways are related to physiological functions and disease states and are influenced by genetic variation and environmental factors. Hispanics/Latino individuals have ancestry-derived genomic regions (local ancestry) from their recent admixture that have been less characterized for associations with metabolite abundance and disease risk.

Methods: We performed admixture mapping of 640 circulating metabolites in 3887 Hispanic/Latino individuals from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Metabolites were quantified in fasting serum through non-targeted mass spectrometry (MS) analysis using ultra-performance liquid chromatography-MS/MS. Replication was performed in 1856 nonoverlapping HCHS/SOL participants with metabolomic data.

Results: By leveraging local ancestry, this study identified significant ancestry-enriched associations for 78 circulating metabolites at 484 independent regions, including 116 novel metabolite-genomic region associations that replicated in an independent sample. Among the main findings, we identified Native American enriched genomic regions at chromosomes 11 and 15, mapping to FADS1/FADS2 and LIPC, respectively, associated with reduced long-chain polyunsaturated fatty acid metabolites implicated in metabolic and inflammatory pathways. An African-derived genomic region at chromosome 2 was associated with N-acetylated amino acid metabolites. This region, mapped to ALMS1, is associated with chronic kidney disease, a disease that disproportionately burdens individuals of African descent.

Conclusions: Our findings provide important insights into differences in metabolite quantities related to ancestry in admixed populations including metabolites related to regulation of lipid polyunsaturated fatty acids and N-acetylated amino acids, which may have implications for common diseases in populations.

Keywords: Admixture mapping; Hispanics/Latino populations; Local ancestry; Metabolites.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • American Indian or Alaska Native / genetics
  • Black People / genetics
  • Genome, Human
  • Genome-Wide Association Study* / methods
  • Hispanic or Latino* / genetics
  • Humans
  • Metabolism / genetics
  • Polymorphism, Single Nucleotide
  • Population Groups / ethnology
  • Population Groups / genetics
  • Tandem Mass Spectrometry*