Zhou Jiayi, Indik Claire E, Kuipers Thomas B, Li Chihua, Nivard Michel G, Ryan Calen P, Tucker-Drob Elliot M, Taeubert M Jazmin, Wang Shuang, Wang Tian, Conley Dalton, Heijmans Bastiaan T, Lumey Lambert H, Belsky Daniel W
Robert N. Butler Columbia Aging Center, Columbia University, New York, NY, USA.
Department of Biomedical Data Sciences, Sequencing Analysis Support Core, Leiden University Medical Center, Leiden, The Netherlands.
Am J Epidemiol. 2024 Oct 2;194(7):1959-66. doi: 10.1093/aje/kwae376.
Natural-experiment designs that compare survivors of in-utero famine exposure to unaffected controls suggest that in-utero undernutrition predisposes to development of obesity. However, birth rates drop dramatically during famines. Selection bias could arise if factors that contribute to obesity also protect fertility and/or fetal survival under famine conditions. We investigated this hypothesis using genetic analysis of a famine-exposed birth cohort. We genotyped participants in the Dutch Hunger Winter Families Study (DHWFS, N=950; 45% male), of whom 51% were exposed to the 1944-1945 Dutch Famine during gestation and 49% were their unexposed same-sex siblings or "time controls" born before or after the famine in the same hospitals. We computed body-mass index (BMI) polygenic indices (PGIs) in DHWFS participants and compared BMI PGIs between famine-exposed and control groups. Participants with higher polygenic risk had higher BMIs (Pearson r=0.42, p<0.001). However, differences between BMI PGIs of famine-exposed participants and controls were small and not statistically different from zero across specifications (Cohen's d=0.10, p>0.092). Our findings did not indicate selection bias, supporting the validity of the natural-experiment design within DHWFS. In summary, our study outlines a novel approach to explore the presence of selection bias in famine and other natural experiment studies.
将子宫内暴露于饥荒的幸存者与未受影响的对照组进行比较的自然实验设计表明，子宫内营养不良易导致肥胖的发生。然而，饥荒期间出生率会大幅下降。如果导致肥胖的因素在饥荒条件下也能保护生育能力和/或胎儿存活，就可能会出现选择偏差。我们通过对一个经历过饥荒的出生队列进行基因分析来研究这一假设。我们对荷兰饥荒冬季家庭研究（DHWFS，N = 950；45%为男性）中的参与者进行了基因分型，其中51%在孕期暴露于1944 - 1945年的荷兰饥荒，49%是他们未暴露的同性兄弟姐妹或在同一医院饥荒前后出生的“时间对照组”。我们计算了DHWFS参与者的体重指数（BMI）多基因指数（PGIs），并比较了饥荒暴露组和对照组之间的BMI PGIs。多基因风险较高的参与者BMI也较高（皮尔逊r = 0.42，p < 0.001）。然而，饥荒暴露参与者和对照组的BMI PGIs之间的差异很小，在所有设定下与零无统计学差异（科恩d = 0.10，p > 0.092）。我们的研究结果未表明存在选择偏差，支持了DHWFS中自然实验设计的有效性。总之，我们的研究概述了一种探索饥荒及其他自然实验研究中选择偏差存在情况的新方法。
