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

Genome Medicine

Research

Laura Y. Zhou¹  Bridget M. Lin¹  Jianwen Cai¹  Kaylia M. Reynolds²  Andrea R. V. R. Horimoto³  Sharon R. Browning³  Qibin Qi⁴  Robert Kaplan⁵  Nora Franceschini⁶  Saame Raza Shaikh⁷  Lifang Hou⁸  Ying Zhang⁹  Nuzulul Kurniansyah⁹  Tamar Sofer^1,10  Bing Yu^1,11  Eric Boerwinkle^1,11  Martha Daviglus^1,12 

[1] Department of Biostatistics, University of North Carolina, Chapel Hill, NC, USA;Department of Biostatistics, University of North Carolina, Chapel Hill, NC, USA;Department of Epidemiology, University of North Carolina, 123 W Franklin St, Suite 401, NC 27516, Chapel Hill, NC, USA;Department of Biostatistics, University of Washington, Seattle, WA, USA;Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA;Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA;Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA;Department of Epidemiology, University of North Carolina, 123 W Franklin St, Suite 401, NC 27516, Chapel Hill, NC, USA;Department of Nutrition, University of North Carolina, Chapel Hill, NC, USA;Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA;Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital, Boston, MA, USA;Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital, Boston, MA, USA;Departments of Medicine and Biostatistics, Harvard University, Boston, MA, USA;Human Genetics Center, University of Texas Health Science Center at Houston, Houston, TX, USA;Institute for Minority Health Research, University of Illinois at Chicago, Chicago, IL, USA;

关键词: Admixture mapping;    Local ancestry;    Metabolites;    Hispanics/Latino populations;   

DOI  :  10.1186/s13073-023-01209-z

 received in 2022-11-22, accepted in 2023-07-10,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundMetabolic 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.MethodsWe 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.ResultsBy 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.ConclusionsOur 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.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

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