Australian Centre for Precision Health, Unit of Clinical and Health Sciences, University of South Australia, North Terrace, Adelaide, SA, 5000, Australia.
Population, Policy and Practice, UCL Great Ormond Street Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK.
Int J Obes (Lond). 2022 Jan;46(1):77-84. doi: 10.1038/s41366-021-00962-8. Epub 2021 Sep 8.
High body mass index (BMI) is an important predictor of mortality but estimating underlying causality is hampered by confounding and pre-existing disease. Here, we use information from the offspring to approximate parental BMIs, with an aim to avoid biased estimation of mortality risk caused by reverse causality.
The analyses were based on information on 9674 offspring-mother and 9096 offspring-father pairs obtained from the 1958 British birth cohort. Parental BMI-mortality associations were analysed using conventional methods and using offspring BMI as a proxy, or instrument, for their parents' BMI.
In the conventional analysis, associations between parental BMI and all-cause mortality were U-shaped (P < 0.001), while offspring BMI had linear associations with parental mortality (P < 0.001, P > 0.46). Curvature was particularly pronounced for mortality from respiratory diseases and from lung cancer. Instrumental variable analyses suggested a positive association between BMI and mortality from all causes [mothers: HR per SD of BMI 1.43 (95% CI 1.21-1.69), fathers: HR 1.17 (1.00-1.36)] and from coronary heart disease [mothers: HR 1.65 (1.15-2.36), fathers: HR 1.51 (1.17-1.97)]. These were larger than HR from the equivalent conventional analyses, despite some attenuation by adjustment for social indicators and smoking.
Analyses using offspring BMI as a proxy for parental BMI suggest that the apparent adverse consequences of low BMI are considerably overestimated and adverse consequences of overweight are underestimated in conventional epidemiological studies.
高体重指数（BMI）是死亡率的一个重要预测因素，但由于混杂因素和既有疾病的存在，估计其因果关系受到了阻碍。在这里，我们使用来自子女的信息来估计父母的 BMI，目的是避免因反向因果关系导致死亡率风险的估计出现偏差。
该分析基于从 1958 年英国出生队列中获得的 9674 对子女-母亲和 9096 对子女-父亲信息。使用传统方法和子女 BMI 作为父母 BMI 的代理或工具，分析父母 BMI 与死亡率之间的关联。
在传统分析中，父母 BMI 与全因死亡率之间呈 U 形关联（P<0.001），而子女 BMI 与父母死亡率呈线性关联（P<0.001，P>0.46）。这种曲线关系在呼吸系统疾病和肺癌死亡率方面尤为明显。工具变量分析表明，BMI 与所有原因导致的死亡率呈正相关[母亲：每标准差 BMI 的 HR 为 1.43（95%CI 1.21-1.69），父亲：HR 为 1.17（1.00-1.36）]，与冠心病死亡率呈正相关[母亲：HR 为 1.65（1.15-2.36），父亲：HR 为 1.51（1.17-1.97）]。这些结果大于等效的传统分析中的 HR，尽管通过调整社会指标和吸烟情况进行了一些调整。
使用子女 BMI 作为父母 BMI 的代理进行分析表明，在传统的流行病学研究中，低 BMI 的不良后果被大大高估，超重的不良后果被低估。
