Metabolic diversity in human populations and correlation with genetic and ancestral geographic distances.
Metabolic diversity in human populations and correlation with genetic and ancestral geographic distances.
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DOI：
10.1016/j.ymgme.2022.10.002
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发表时间：
2022-11
影响因子：
3.8
通讯作者：
Scharfe, Curt
中科院分区：
文献类型：
--
作者：
Peng, Gang;Pakstis, Andrew J.;Gandotra, Neeru;Cowan, Tina M.;Zhao, Hongyu;Kidd, Kenneth K.;Scharfe, Curt
关键词：
DNA多态性标记和自我定义的种族分组被用来对具有共同的古代地理祖先的个体进行分组。在这里，我们研究了个体之间的祖先关系是否可以从加州新生儿筛查（NBS）项目报告的代谢筛查数据中识别出来。国家统计局的数据包括41个血液代谢物测量的串联质谱从单胎婴儿在17个父母报告的种族分组。71%的NBS代谢物（29/41，Cohen's d > 0.5）的种族相关差异表明，血液中酰基肉毒碱水平的差异大于氨基酸水平（P <1 e-4）。代谢距离测量，开发比较基于代谢差异的种族分组，显示出低的正相关性与遗传和古老的地理距离之间的群体的祖先世界人口。确定了几个离群值组对，遗传距离较大，代谢距离较小（黑人与白色），或遗传距离较小，代谢距离较大（中国人与日本人），表明遗传和环境因素对代谢的影响。使用机器学习，比较所有种族群体之间的代谢谱，区分具有较大遗传距离的个体（黑人与中国人，AUC = 0.96），而遗传上更相似的个体无法在代谢上分开（西班牙裔与美洲原住民，AUC = 0.51）。此外，我们还鉴定了可用于推断遗传相似人群个体代谢祖先的代谢物，包括先天性代谢紊乱的生物标志物（C10：1、C12：1、C3、C5 OH、亮氨酸-异亮氨酸）。这项工作为不同人群中健康新生儿的代谢差异提供了新的线索，这可能对改善遗传疾病筛查具有重要意义。
DNA polymorphic markers and self-defined ethnicity groupings are used to group individuals with shared ancient geographic ancestry. Here we studied whether ancestral relationships between individuals could be identified from metabolic screening data reported by the California newborn screening (NBS) program. NBS data includes 41 blood metabolites measured by tandem mass spectrometry from singleton babies in 17 parent-reported ethnicity groupings. Ethnicity-associated differences identified for 71% of NBS metabolites (29 of 41, Cohen's d > 0.5) showed larger differences in blood levels of acylcarnitines than of amino acids (P < 1e-4). Ametabolic distance measure, developed to compare ethnic groupings based on metabolic differences, showed low positive correlation with genetic and ancient geographic distances between the groups' ancestral world populations. Several outlier group pairs were identified with larger genetic and smaller metabolic distances (Black versus White) or with smaller genetic and larger metabolic distances (Chinese versus Japanese) indicating the influence of genetic and of environmental factors on metabolism. Using machine learning, comparison of metabolic profiles between all pairs of ethnic groupings distinguished individuals with larger genetic distance (Black versus Chinese, AUC = 0.96), while genetically more similar individuals could not be separated metabolically (Hispanic versus Native American, AUC = 0.51). Additionally, we identified metabolites informative for inferring metabolic ancestry in individuals from genetically similar populations, which included biomarkers for inborn metabolic disorders (C10:1, C12:1, C3, C5OH, Leucine-Isoleucine). This work sheds new light on metabolic differences in healthy newborns in diverse populations, which could have implications for improving genetic disease screening.
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影响因子：
56.9
作者：
Rosenberg, NA;Pritchard, JK;Feldman, MW
通讯作者：
Feldman, MW
影响因子：
5.8
作者：
Gu, Zuguang;Eils, Roland;Schlesner, Matthias
通讯作者：
Schlesner, Matthias
影响因子：
5.3
作者：
Hebbar P;Abubaker JA;Abu-Farha M;Alsmadi O;Elkum N;Alkayal F;John SE;Channanath A;Iqbal R;Pitkaniemi J;Tuomilehto J;Sladek R;Al-Mulla F;Thanaraj TA
通讯作者：
Thanaraj TA
影响因子：
3.1
作者：
Kidd, Kenneth K.;Soundararajan, Usha;Ropero-Miller, Jeri D.
通讯作者：
Ropero-Miller, Jeri D.
影响因子：
3.5
作者：
Peng, Gang;Tang, Yishuo;Scharfe, Curt
通讯作者：
Scharfe, Curt