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, NC 27516, Chapel Hill, USA.
Genome Med. 2023 Jul 17;15(1):52. doi: 10.1186/s13073-023-01209-z.
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.
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.
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.
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.
代谢途径与生理功能和疾病状态有关，受遗传变异和环境因素的影响。西班牙裔/拉丁裔个体的近期混合血统中存在源于祖先的基因组区域（局部祖先），这些区域与代谢物丰度和疾病风险的相关性尚未得到充分描述。
我们对来自西班牙裔社区健康研究/拉丁裔研究（HCHS/SOL）的 3887 名西班牙裔/拉丁裔个体的 640 种循环代谢物进行了混合映射。通过非靶向质谱（MS）分析，使用超高效液相色谱-MS/MS 对空腹血清中的代谢物进行定量。在具有代谢组学数据的 1856 名不重叠的 HCHS/SOL 参与者中进行了复制。
通过利用局部祖先，本研究在 484 个独立区域中确定了 78 种循环代谢物的显著祖先富集关联，其中包括 116 个新的代谢物-基因组区域关联，在独立样本中得到了复制。主要发现包括在染色体 11 和 15 上发现了美洲原住民富集的基因组区域，分别映射到 FADS1/FADS2 和 LIPC，与代谢和炎症途径中涉及的长链多不饱和脂肪酸代谢物减少有关。染色体 2 上的一个非洲衍生的基因组区域与 N-乙酰化氨基酸代谢物有关。该区域映射到 ALMS1，与慢性肾病有关，这种疾病在非洲裔个体中负担过重。
我们的研究结果为混合人群中与祖先相关的代谢物数量差异提供了重要的见解，包括与脂质多不饱和脂肪酸和 N-乙酰化氨基酸调节相关的代谢物，这些代谢物可能对人群中的常见疾病有影响。
