Ancestry-driven metabolite variation provides insights into disease states in admixed populations
© 2023. The Author(s)..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
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| Enthalten in: |
Genome medicine - 15(2023), 1 vom: 17. Juli, Seite 52 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Reynolds, Kaylia M [VerfasserIn] |
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| Links: |
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| Themen: |
Admixture mapping |
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| Anmerkungen: |
Date Completed 25.07.2023 Date Revised 26.04.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1186/s13073-023-01209-z |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM359615961 |
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| 100 | 1 | |a Reynolds, Kaylia M |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Ancestry-driven metabolite variation provides insights into disease states in admixed populations |
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| 500 | |a Date Revised 26.04.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023. The Author(s). | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Admixture mapping | |
| 650 | 4 | |a Hispanics/Latino populations | |
| 650 | 4 | |a Local ancestry | |
| 650 | 4 | |a Metabolites | |
| 700 | 1 | |a Horimoto, Andrea R V R |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Bridget M |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Ying |e verfasserin |4 aut | |
| 700 | 1 | |a Kurniansyah, Nuzulul |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Bing |e verfasserin |4 aut | |
| 700 | 1 | |a Boerwinkle, Eric |e verfasserin |4 aut | |
| 700 | 1 | |a Qi, Qibin |e verfasserin |4 aut | |
| 700 | 1 | |a Kaplan, Robert |e verfasserin |4 aut | |
| 700 | 1 | |a Daviglus, Martha |e verfasserin |4 aut | |
| 700 | 1 | |a Hou, Lifang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Laura Y |e verfasserin |4 aut | |
| 700 | 1 | |a Cai, Jianwen |e verfasserin |4 aut | |
| 700 | 1 | |a Shaikh, Saame Raza |e verfasserin |4 aut | |
| 700 | 1 | |a Sofer, Tamar |e verfasserin |4 aut | |
| 700 | 1 | |a Browning, Sharon R |e verfasserin |4 aut | |
| 700 | 1 | |a Franceschini, Nora |e verfasserin |4 aut | |
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