Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol, United Kingdom.
MRC Unit for Lifelong Health and Ageing at UCL, Department of Population Science and Experimental Medicine, Institute of Cardiovascular Science, University College London, London, United Kingdom.
PLoS Biol. 2022 Jun 9;20(6):e3001656. doi: 10.1371/journal.pbio.3001656. eCollection 2022 Jun.
Children with obesity typically have larger left ventricular heart dimensions during adulthood. However, whether this is due to a persistent effect of adiposity extending into adulthood is challenging to disentangle due to confounding factors throughout the lifecourse. We conducted a multivariable mendelian randomization (MR) study to separate the independent effects of childhood and adult body size on 4 magnetic resonance imaging (MRI) measures of heart structure and function in the UK Biobank (UKB) study. Strong evidence of a genetically predicted effect of childhood body size on all measures of adulthood heart structure was identified, which remained robust upon accounting for adult body size using a multivariable MR framework (e.g., left ventricular end-diastolic volume (LVEDV), Beta = 0.33, 95% confidence interval (CI) = 0.23 to 0.43, P = 4.6 × 10-10). Sensitivity analyses did not suggest that other lifecourse measures of body composition were responsible for these effects. Conversely, evidence of a genetically predicted effect of childhood body size on various other MRI-based measures, such as fat percentage in the liver (Beta = 0.14, 95% CI = 0.05 to 0.23, P = 0.002) and pancreas (Beta = 0.21, 95% CI = 0.10 to 0.33, P = 3.9 × 10-4), attenuated upon accounting for adult body size. Our findings suggest that childhood body size has a long-term (and potentially immutable) influence on heart structure in later life. In contrast, effects of childhood body size on other measures of adulthood organ size and fat percentage evaluated in this study are likely explained by the long-term consequence of remaining overweight throughout the lifecourse.
儿童肥胖症患者成年后患左心室心脏尺寸通常较大。然而，由于整个生命过程中存在混杂因素，因此很难确定这种情况是由于肥胖的持续影响延伸到成年期。我们进行了一项多变量孟德尔随机化（MR）研究，以分离儿童期和成年期身体大小对英国生物库（UKB）研究中 4 种心脏结构和功能磁共振成像（MRI）测量的独立影响。强有力的证据表明，儿童期身体大小对成年期心脏结构的所有测量值都有遗传预测作用，并且在使用多变量 MR 框架（例如，左心室舒张末期容积（LVEDV），Beta = 0.33，95%置信区间（CI）= 0.23 至 0.43，P = 4.6 × 10-10）考虑到成年期身体大小时，这种影响仍然很稳健。敏感性分析表明，其他生命过程中身体成分的测量值不是造成这些影响的原因。相反，有证据表明，儿童期身体大小对各种其他基于 MRI 的测量值（例如肝脏脂肪百分比（Beta = 0.14，95%CI = 0.05 至 0.23，P = 0.002）和胰腺（Beta = 0.21，95%CI = 0.10 至 0.33，P = 3.9 × 10-4））有遗传预测作用，但在考虑到成年期身体大小时会减弱。我们的研究结果表明，儿童期身体大小对晚年心脏结构有长期（可能是不可改变的）影响。相比之下，在本研究中评估的成年期器官大小和脂肪百分比的儿童期身体大小的影响很可能是由于整个生命过程中持续超重的长期后果所解释的。
