School of Social and Community Medicine, University of Bristol, Bristol, UK.
BMC Med Genet. 2012 Sep 27;13:90. doi: 10.1186/1471-2350-13-90.
In observational epidemiological studies type 2 diabetes (T2D) and both low and high plasma concentrations of fasting glucose have been found to be associated with lower cognitive performance. These associations could be explained by confounding.
In this study we looked at the association between genetic variants, known to be robustly associated with fasting glucose and T2D risk, in the mother and her offspring to determine whether there is likely to be a causal link between early life exposure to glucose and child's intelligence quotient (IQ) scores in the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. We generated a fasting glucose (FGGRS) and a T2D (T2DGRS) genetic risk score and used them in a Mendelian randomization approach.
We found a strong correlation between the FGGRS and fasting glucose plasma measurements that were available for a subset of children, but no association of either the maternal or the offspring FGGRS with child's IQ was observed. In contrast, the maternal T2DGRS was positively associated with offspring IQ.
Maternal and offspring genetic variants which are associated with glucose levels are not associated with offspring IQ, suggesting that there is unlikely to be a causal link between glucose exposure in utero and IQ in childhood. Further exploration in even larger cohorts is required to exclude the possibility that our null findings were due to a lack of statistical power.
在观察性流行病学研究中，2 型糖尿病（T2D）以及空腹血糖的低浓度和高浓度均与认知表现降低相关。这些关联可能是由混杂因素引起的。
在这项研究中，我们研究了已知与空腹血糖和 T2D 风险密切相关的母亲及其后代中的遗传变异与早期暴露于葡萄糖和儿童智商（IQ）分数之间的因果关系在阿冯纵向父母和子女研究（ALSPAC）队列中。我们生成了空腹血糖（FGGRS）和 T2D（T2DGRS）遗传风险评分，并在 Mendelian 随机化方法中使用了这些评分。
我们发现 FGGRS 与可用于部分儿童的空腹血糖血浆测量值之间存在很强的相关性，但未观察到母体或后代 FGGRS 与儿童 IQ 之间存在任何关联。相比之下，母体 T2DGRS 与后代 IQ 呈正相关。
与血糖水平相关的母体和后代遗传变异与后代的 IQ 无关，这表明宫内葡萄糖暴露与儿童时期的 IQ 之间不太可能存在因果关系。需要在更大的队列中进行进一步探索，以排除我们的无效发现是由于缺乏统计学效力的可能性。
