Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
Amsterdam Public Health Research Institute, Amsterdam, the Netherlands.
Twin Res Hum Genet. 2020 Jun;23(3):145-155. doi: 10.1017/thg.2020.53.
Metabolites are small molecules involved in cellular metabolism where they act as reaction substrates or products. The term 'metabolomics' refers to the comprehensive study of these molecules. The concentrations of metabolites in biological tissues are under genetic control, but this is limited by environmental factors such as diet. In adult mono- and dizygotic twin pairs, we estimated the contribution of genetic and shared environmental influences on metabolite levels by structural equation modeling and tested whether the familial resemblance for metabolite levels is mainly explained by genetic or by environmental factors that are shared by family members. Metabolites were measured across three platforms: two based on proton nuclear magnetic resonance techniques and one employing mass spectrometry. These three platforms comprised 237 single metabolic traits of several chemical classes. For the three platforms, metabolites were assessed in 1407, 1037 and 1116 twin pairs, respectively. We carried out power calculations to establish what percentage of shared environmental variance could be detected given these sample sizes. Our study did not find evidence for a systematic contribution of shared environment, defined as the influence of growing up together in the same household, on metabolites assessed in adulthood. Significant heritability was observed for nearly all 237 metabolites; significant contribution of the shared environment was limited to 6 metabolites. The top quartile of the heritability distribution was populated by 5 of the 11 investigated chemical classes. In this quartile, metabolites of the class lipoprotein were significantly overrepresented, whereas metabolites of classes glycerophospholipids and glycerolipids were significantly underrepresented.
代谢物是参与细胞代谢的小分子，它们作为反应底物或产物发挥作用。“代谢组学”一词指的是对这些分子的综合研究。生物组织中代谢物的浓度受遗传控制，但这受到饮食等环境因素的限制。在成年单卵和双卵双胞胎中，我们通过结构方程建模来估计遗传和共同环境因素对代谢物水平的影响，并检验代谢物水平的家族相似性主要是由遗传因素还是由家庭成员共同的环境因素来解释。代谢物是通过三个平台来测量的：两个基于质子核磁共振技术，一个基于质谱技术。这三个平台包括 237 种化学类别的单一代谢特征。对于这三个平台，分别在 1407、1037 和 1116 对双胞胎中评估了代谢物。我们进行了功效计算，以确定在这些样本量下可以检测到共享环境方差的百分比。我们的研究没有发现共同环境（定义为在同一个家庭中共同成长的影响）对成年期评估的代谢物有系统贡献的证据。几乎所有 237 种代谢物都表现出显著的遗传力；共同环境的显著贡献仅限于 6 种代谢物。遗传力分布的前四分之一由 11 个研究的化学类别的 5 个组成。在这个四分之一中，脂蛋白类的代谢物显著过剩，而甘油磷脂和甘油酯类的代谢物则显著不足。
