Draisma Harmen H M, Beekman Marian, Pool René, van Ommen Gert-Jan B, Adamski Jerzy, Prehn Cornelia, Vaarhorst Anika A M, de Craen Anton J M, Willemsen Gonneke, Slagboom P Eline, Boomsma Dorret I
Department of Biological Psychology, Faculty of Psychology and Education, VU University Amsterdam, The Netherlands.
Twin Res Hum Genet. 2013 Oct;16(5):948-61. doi: 10.1017/thg.2013.59. Epub 2013 Aug 28.
Metabolomics is the comprehensive study of metabolites, which are the substrates, intermediate, and end products of cellular metabolism. The heritability of the concentrations of circulating metabolites bears relevance for evaluating their suitability as biomarkers for disease. We report aspects of familial resemblance for the concentrations in human serum of more than 100 metabolites, measured using a targeted metabolomics platform. Age- and sex-corrected monozygotic twin correlations, midparent-offspring regression coefficients, and spouse correlations in subjects from two independent cohorts (Netherlands Twin Register and Leiden Longevity Study) were estimated for each metabolite. In the Netherlands Twin Register subjects, who were largely fasting, we found significant monozygotic twin correlations for 121 out of 123 metabolites. Heritability was confirmed by midparent-offspring regression. For most detected metabolites, the correlations between spouses were considerably lower than those between twins, indicating a contribution of genetic effects to familial resemblance. Remarkably high heritability was observed for free carnitine (monozygotic twin correlation 0.66), for the amino acids serine (monozygotic twin correlation 0.77) and threonine (monozygotic twin correlation 0.64), and for phosphatidylcholine acyl-alkyl C40:3 (monozygotic twin correlation 0.77). For octenoylcarnitine, a consistent point estimate of approximately 0.50 was found for the spouse correlations in the two cohorts as well as for the monozygotic twin correlation, suggesting that familiality for this metabolite is explained by shared environment. We conclude that for the majority of metabolites targeted by the used metabolomics platform, the familial resemblance of serum concentrations is largely genetic. Our results contribute to the knowledge of the heritability of fasting serum metabolite concentrations, which is relevant for biomarker research.
代谢组学是对代谢物的全面研究，代谢物是细胞代谢的底物、中间产物和终产物。循环代谢物浓度的遗传力对于评估其作为疾病生物标志物的适用性具有重要意义。我们报告了使用靶向代谢组学平台测量的100多种人类血清代谢物浓度的家族相似性方面。对来自两个独立队列（荷兰双胞胎登记处和莱顿长寿研究）的受试者，针对每种代谢物估计了年龄和性别校正后的同卵双胞胎相关性、中亲-子代回归系数以及配偶相关性。在荷兰双胞胎登记处的受试者中，他们大多处于空腹状态，我们发现123种代谢物中有121种存在显著的同卵双胞胎相关性。中亲-子代回归证实了遗传力。对于大多数检测到的代谢物，配偶之间的相关性远低于双胞胎之间的相关性，表明遗传效应是家族相似性的一个因素。观察到游离肉碱（同卵双胞胎相关性为0.66）、氨基酸丝氨酸（同卵双胞胎相关性为0.77）和苏氨酸（同卵双胞胎相关性为0.64）以及磷脂酰胆碱酰基-烷基C40:3（同卵双胞胎相关性为0.77）具有非常高的遗传力。对于辛酰肉碱，在两个队列中配偶相关性以及同卵双胞胎相关性的一致点估计约为0.50，这表明这种代谢物的家族性是由共同环境解释的。我们得出结论，对于所使用的代谢组学平台靶向的大多数代谢物，血清浓度的家族相似性在很大程度上是由遗传因素决定的。我们的结果有助于了解空腹血清代谢物浓度的遗传力，这与生物标志物研究相关。
