Accessibility issues or difficulties with this website?
Call 919-962-2073 or email hchsadministration@unc.edu.

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

TitleAncestry-driven metabolite variation provides insights into disease states in admixed populations.
Publication TypePublication
Year2023
AuthorsReynolds KM, Horimoto ARVR, Lin BM, Zhang Y, Kurniansyah N, Yu B, Boerwinkle E, Qi Q, Kaplan R, Daviglus M, Hou L, Zhou LY, Cai J, Shaikh SRaza, Sofer T, Browning SR, Franceschini N
JournalGenome Med
Volume15
Issue1
Pagination52
Date Published2023 Jul 17
ISSN1756-994X
KeywordsAmerican Indian or Alaska Native, Black People, Genome, Human, genome-wide association study, Hispanic or Latino, Humans, metabolism, Polymorphism, Single Nucleotide, Population Groups, Tandem Mass Spectrometry
Abstract

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.

DOI10.1186/s13073-023-01209-z
Alternate JournalGenome Med
PubMed ID37461045
PubMed Central IDPMC10351197
Grant ListN01HC65235 / HL / NHLBI NIH HHS / United States
N01HC65233 / HL / NHLBI NIH HHS / United States
P30 DK020541 / DK / NIDDK NIH HHS / United States
R01 MD012765 / MD / NIMHD NIH HHS / United States
P30 ES010126 / ES / NIEHS NIH HHS / United States
N01HC65236 / HL / NHLBI NIH HHS / United States
N01HC65237 / HL / NHLBI NIH HHS / United States
R01 DK117445 / DK / NIDDK NIH HHS / United States
N01HC65234 / HL / NHLBI NIH HHS / United States
MS#: 
1151
Manuscript Lead/Corresponding Author Affiliation: 
Coordinating Center - Collaborative Studies Coordinating Center - UNC at Chapel Hill
ECI: 
Manuscript Affiliation: 
Coordinating Center - Collaborative Studies Coordinating Center - UNC at Chapel Hill
Manuscript Status: 
Published