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

Kaylia M. Reynolds; Andrea R.V.R. Horimoto; Bridget M. Lin; Ying Zhang; Nuzulul Kurniansyah; Bing Yu; Eric Boerwinkle; Qibin Qi; Robert Kaplan; Martha Daviglus; Lifang Hou; Laura Y. Zhou; Jianwen Cai; Saame Raza Shaikh; Tamar Sofer; Sharon R. Browning; Nora Franceschini

doi:10.1186/s13073-023-01209-z

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

Kaylia M. Reynolds, Andrea R.V.R. Horimoto, Bridget M. Lin, Ying Zhang, Nuzulul Kurniansyah, Bing Yu, Eric Boerwinkle, Qibin Qi, Robert Kaplan, Martha Daviglus, Lifang Hou, Laura Y. Zhou, Jianwen Cai, Saame Raza Shaikh, Tamar Sofer, Sharon R. Browning, Nora Franceschini^*

^*Corresponding author for this work

Preventive Medicine

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

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.

Original language	English (US)
Article number	52
Journal	Genome Medicine
Volume	15
Issue number	1
DOIs	https://doi.org/10.1186/s13073-023-01209-z
State	Published - Dec 2023

Funding

HCHS/SOL is a collaborative study supported by contracts from the National Heart, Lung, and Blood Institute (NHLBI) to the University of North Carolina (HHSN268201300001I /N01-HC-65233), University of Miami (HHSN268201300004I / N01-HC-65234), Albert Einstein College of Medicine (HHSN268201300002I / N01-HC-65235), University of Illinois at Chicago (HHSN268201300003I / N01-HC-65236 Northwestern Univ), and San Diego State University (HHSN268201300005I / N01-HC-65237). The following Institutes/Centers/Offices have contributed to the HCHS/SOL through a transfer of funds to the NHLBI: National Institute on Minority Health and Health Disparities, National Institute on Deafness and Other Communication Disorders, National Institute of Dental and Craniofacial Research, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, NIH Institution-Office of Dietary Supplements. This project was supported by NIH R01 DK117445 and R01 MD012765 (to NF). Support for metabolomics data was graciously provided by the JLH Foundation (Houston, Texas).

Keywords

Admixture mapping
Hispanics/Latino populations
Local ancestry
Metabolites

ASJC Scopus subject areas

Molecular Medicine
Molecular Biology
Genetics
Genetics(clinical)

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10.1186/s13073-023-01209-z

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Reynolds, K. M., Horimoto, A. R. V. R., Lin, B. M., Zhang, Y., Kurniansyah, N., Yu, B., Boerwinkle, E., Qi, Q., Kaplan, R., Daviglus, M., Hou, L., Zhou, L. Y., Cai, J., Shaikh, S. R., Sofer, T., Browning, S. R., & Franceschini, N. (2023). Ancestry-driven metabolite variation provides insights into disease states in admixed populations. Genome Medicine, 15(1), Article 52. https://doi.org/10.1186/s13073-023-01209-z

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title = "Ancestry-driven metabolite variation provides insights into disease states in admixed populations",

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.",

keywords = "Admixture mapping, Hispanics/Latino populations, Local ancestry, Metabolites",

author = "Reynolds, {Kaylia M.} and Horimoto, {Andrea R.V.R.} and Lin, {Bridget M.} and Ying Zhang and Nuzulul Kurniansyah and Bing Yu and Eric Boerwinkle and Qibin Qi and Robert Kaplan and Martha Daviglus and Lifang Hou and Zhou, {Laura Y.} and Jianwen Cai and Shaikh, {Saame Raza} and Tamar Sofer and Browning, {Sharon R.} and Nora Franceschini",

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

month = dec,

doi = "10.1186/s13073-023-01209-z",

language = "English (US)",

volume = "15",

journal = "Genome Medicine",

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Reynolds, 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, SR, Sofer, T, Browning, SR & Franceschini, N 2023, 'Ancestry-driven metabolite variation provides insights into disease states in admixed populations', Genome Medicine, vol. 15, no. 1, 52. https://doi.org/10.1186/s13073-023-01209-z

TY - JOUR

T1 - Ancestry-driven metabolite variation provides insights into disease states in admixed populations

AU - Reynolds, Kaylia M.

AU - Horimoto, Andrea R.V.R.

AU - Lin, Bridget M.

AU - Zhang, Ying

AU - Kurniansyah, Nuzulul

AU - Yu, Bing

AU - Boerwinkle, Eric

AU - Qi, Qibin

AU - Kaplan, Robert

AU - Daviglus, Martha

AU - Hou, Lifang

AU - Zhou, Laura Y.

AU - Cai, Jianwen

AU - Shaikh, Saame Raza

AU - Sofer, Tamar

AU - Browning, Sharon R.

AU - Franceschini, Nora

PY - 2023/12

Y1 - 2023/12

N2 - 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.

AB - 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.

KW - Admixture mapping

KW - Hispanics/Latino populations

KW - Local ancestry

KW - Metabolites

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DO - 10.1186/s13073-023-01209-z

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SN - 1756-994X

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JO - Genome Medicine

JF - Genome Medicine

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ER -

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

Abstract

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Keywords

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