Qian Li, Gao Fengjie, Yan Bin, Yang Lihong, Wang Wei, Bai Ling, Ma Xiancang, Yang Jian
Department of Psychological Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Clinical Research Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Brain Behav. 2021 Jun;11(6):e02183. doi: 10.1002/brb3.2183. Epub 2021 May 10.
Birth parameters have long been reported to have a role in human intelligence. However, the causalities reported in previous observational studies were controversial. Our study aims to provide an unbiased investigation of the causal associations between birth parameters and human intelligence using the Mendelian randomization (MR) approach.
Genetic instrumental variables for MR analyses were extracted from large genome-wide association studies of infant head circumference (N = 10,768), birth length (N = 28,489), and birth weight (N = 321,223). Data for intelligence were obtained from a meta-analysis of genome-wide association studies of 269,867 individuals of the European ancestry. Primary MR analysis was performed using the standard inverse-variance weighted method, and sensitivity analyses were performed using the weighted median, MR-Egger, and MR-PRESSO methods.
Using 10 single nucleotide polymorphisms as instrumental variables, we found that 1 standard deviation increase in infant head circumference was associated with 0.14-fold higher scores in intelligence tests (β = 0.14, 95% confidence interval: 0.09 to 0.18, P =2.05 × 10 ). The causal relationship was robust when sensitivity analyses were performed. However, birth length and birth weight had no significant associations with intelligence.
Our findings suggested infant head circumference, but not birth weight and length were associated with intelligence, which might indicate that brain development rather than general fetal growth was responsible for the development of intelligence.
长期以来，出生参数一直被认为对人类智力有影响。然而，以往观察性研究中报告的因果关系存在争议。我们的研究旨在使用孟德尔随机化（MR）方法，对出生参数与人类智力之间的因果关联进行无偏倚调查。
从大规模全基因组关联研究中提取用于MR分析的基因工具变量，这些研究涉及婴儿头围（N = 10768）、出生身长（N = 28489）和出生体重（N = 321223）。智力数据来自对269867名欧洲血统个体的全基因组关联研究的荟萃分析。主要的MR分析使用标准逆方差加权法进行，敏感性分析使用加权中位数、MR-Egger和MR-PRESSO方法进行。
使用10个单核苷酸多态性作为工具变量，我们发现婴儿头围每增加1个标准差，智力测试得分就会高出0.14倍（β = 0.14，95%置信区间：0.09至0.18，P = 2.05×10 ）。进行敏感性分析时，因果关系是稳健的。然而，出生身长和出生体重与智力没有显著关联。
我们的研究结果表明，婴儿头围与智力有关，而出生体重和身长与智力无关，这可能表明大脑发育而非一般胎儿生长对智力发育起作用。
