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祖先驱动的代谢物变异为混合种群中的疾病状态提供了洞察力
Kaylia M Reynolds1,2, Andrea R V R Horimoto3, Bridget M Lin1
1Department of Biostatistics, University of North Carolina, Chapel Hill, NC, USA.
Genome medicine
|July 17, 2023
概括
这项研究将西班牙裔/拉丁裔个体的遗传祖先与特定的代谢物水平联系起来. 研究结果揭示了美洲原住民和非洲祖先如何影响脂肪酸和氨基酸代谢物,影响疾病风险.
科学领域:
- 基因组学和代谢学
- 人口健康 人口健康
- 生物化学 生物化学
背景情况:
- 代谢途径对生理功能和疾病至关重要,受遗传学和环境的影响.
- 西班牙裔/拉丁裔人口拥有独特的当地祖先模式,来自最近的混合,需要进一步描述代谢物协会和疾病风险.
研究的目的:
- 在西班牙裔/拉丁裔个体中调查当地祖先和循环代谢物丰度之间的关联.
- 识别新型代谢物-基因组区域关联及其对常见疾病的潜在影响.
主要方法:
- 在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/拉丁裔参与者中,对640种循环代谢物进行了混合映射.
- 使用非向质谱 (MS) 和超高性能液体色谱-MS/MS. 的量化代谢物.
- 通过在1856名HCHS/SOL参与者的独立样本中复制验证的结果.
主要成果:
- 确定了78种循环代谢物的484个显著的祖先丰富关联,包括116个新的复制关联.
- 在11号和15号染色体上发现了美洲原住民丰富的区域,与减少的多不和脂肪酸代谢物 (通过FADS1/FADS2和LIPC) 相关.
- 在2号染色体上发现了一个非洲衍生的区域,与N-乙化氨基酸代谢物 (通过ALMS1) 相关,可能与慢性病有关.
结论:
- 这项研究阐明了混合种群中代谢物水平的祖先驱动的差异.
- 这些发现突出了特定代谢物的作用 (脂质多不和脂肪酸,N-乙氨基酸) 与祖先的关系.
- 这些见解可能有助于对不同人群中常见疾病病因学的理解.
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