英国布里斯托大学Tom G Richardson研究组宣布取得新进展。他们使用遗传变异来分析早年和成年肥胖对疾病风险的影响。相关论文于2020年5月6日发表在《英国医学杂志》上。
为了评估早年体型是否对晚年患病风险有独立影响，或该影响是否因成年体型介导，研究组使用两样本单变量和多变量孟德尔随机化法，在英国生物银行的前瞻性队列研究中招募了453169名参与者，在四个大规模全基因组关联研究（GWAS）联盟中招募了70多万名参与者。
基于单变量孟德尔随机化分析，早年具有较大基因预测的体重会导致冠状动脉疾病和2型糖尿病的风险增加。但基于多变量孟德尔随机分析并未发现直接影响的证据。在乳腺癌风险的多变量孟德尔随机化分析中，强有力的证据表明早年较大体型有直接保护作用，而成年体型则无直接影响。
包括初潮年龄作为额外暴露提供了总因果效应的弱证据，但直接因果效应的强证据与早年和成年体型无关。没有强有力的证据表明早年或成年体型与前列腺癌有因果关系。
研究结果表明，儿童时期较大体型与成年期患冠心病和2型糖尿病风险之间的正相关关系可归因于其在成年后依然保持较大体型。但无论成年体型如何，在儿童期较小体型都可能增加患乳腺癌的风险，青春期也可能起一定作用。
附：英文原文
Title: Use of genetic variation to separate the effects of early and later life adiposity on disease risk: mendelian randomisation study
Author: Tom G Richardson, Eleanor Sanderson, Benjamin Elsworth, Kate Tilling, George Davey Smith
Issue&Volume: 2020/05/06
Abstract: Objective To evaluate whether body size in early life has an independent effect on risk of disease in later life or whether its influence is mediated by body size in adulthood.
Design Two sample univariable and multivariable mendelian randomisation.
Setting The UK Biobank prospective cohort study and four large scale genome-wide association studies (GWAS) consortiums.
Participants 453169 participants enrolled in UK Biobank and a combined total of more than 700000 people from different GWAS consortiums.
Exposures Measured body mass index during adulthood (mean age 56.5) and self-reported perceived body size at age 10.
Main outcome measures Coronary artery disease, type 2 diabetes, breast cancer, and prostate cancer.
Results Having a larger genetically predicted body size in early life was associated with an increased odds of coronary artery disease (odds ratio 1.49 for each change in body size category unless stated otherwise, 95% confidence interval 1.33 to 1.68) and type 2 diabetes (2.32, 1.76 to 3.05) based on univariable mendelian randomisation analyses. However, little evidence was found of a direct effect (ie, not through adult body size) based on multivariable mendelian randomisation estimates (coronary artery disease: 1.02, 0.86 to 1.22; type 2 diabetes:1.16, 0.74 to 1.82). In the multivariable mendelian randomisation analysis of breast cancer risk, strong evidence was found of a protective direct effect for larger body size in early life (0.59, 0.50 to 0.71), with less evidence of a direct effect of adult body size on this outcome (1.08, 0.93 to 1.27). Including age at menarche as an additional exposure provided weak evidence of a total causal effect (univariable mendelian randomisation odds ratio 0.98, 95% confidence interval 0.91 to 1.06) but strong evidence of a direct causal effect, independent of early life and adult body size (multivariable mendelian randomisation odds ratio 0.90, 0.85 to 0.95). No strong evidence was found of a causal effect of either early or later life measures on prostate cancer (early life body size odds ratio 1.06, 95% confidence interval 0.81 to 1.40; adult body size 0.87, 0.70 to 1.08).
Conclusions The findings suggest that the positive association between body size in childhood and risk of coronary artery disease and type 2 diabetes in adulthood can be attributed to individuals remaining large into later life. However, having a smaller body size during childhood might increase the risk of breast cancer regardless of body size in adulthood, with timing of puberty also putatively playing a role.
DOI: 10.1136/bmj.m1203
Source: https://www.bmj.com/content/369/bmj.m1203
BMJ-British Medical Journal:《英国医学杂志》，创刊于1840年。隶属于BMJ出版集团，最新IF：93.333
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本期文章：《英国医学杂志》：Online/在线发表
