Centorame Giulio, Warrington Nicole M, Hemani Gibran, Wang Geng, Davey Smith George, Evans David M
Institute for Molecular Bioscience, Queensland Bioscience Precinct, The University of Queensland, 306 Carmody Road, St Lucia, QLD, 4072, Australia.
MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Behav Genet. 2025 Mar;55(2):86-102. doi: 10.1007/s10519-024-10210-0. Epub 2024 Dec 9.
Breastfeeding is hypothesised to benefit child health and cognitive functioning by providing long-chain polyunsaturated fatty acids, which are essential for brain development. In 2007, Caspi et al. found evidence in two cohorts for an interaction between genetic variation in the FADS2 gene (a gene involved in fatty acid metabolism) and breastfeeding on IQ. However, subsequent studies have provided mixed evidence for the existence of an interaction. We investigated the relationship between genetic variation in the FADS2 region, breastfeeding, and their interaction in up to 335,650 individuals from the UK Biobank. We tested for the interaction over a range of cognitive functioning tests, as well as educational attainment and other traits thought to be influenced by breastfeeding, including cardiometabolic traits, number of offspring, and atopic allergy. FADS2 alleles associated with an increase in docosahexaenoic acid in blood serum (the C allele of rs174575) were associated with decreased verbal-numerical reasoning ( ) and triglycerides ( ), increased number of offspring ( ), total cholesterol ( ), HDL ( ), and LDL cholesterol ( ). We observed no evidence of an interaction in any of the traits, regardless of the modelling strategy on any cognitive or non-cognitive traits. We postulate that the previous positive findings are likely to be spurious, perhaps due to lack of appropriate control for latent population structure.
母乳喂养被认为通过提供对大脑发育至关重要的长链多不饱和脂肪酸，对儿童健康和认知功能有益。2007年，卡斯皮等人在两个队列中发现了FADS2基因（一种参与脂肪酸代谢的基因）的基因变异与母乳喂养对智商的相互作用的证据。然而，随后的研究对这种相互作用的存在提供了不一致的证据。我们在来自英国生物银行的多达335,650名个体中研究了FADS2区域的基因变异、母乳喂养及其相互作用之间的关系。我们在一系列认知功能测试以及教育程度和其他被认为受母乳喂养影响的特征（包括心脏代谢特征、后代数量和特应性过敏）中测试了这种相互作用。与血清中二十二碳六烯酸增加相关的FADS2等位基因（rs174575的C等位基因）与言语数字推理能力下降（ ）和甘油三酯（ ）、后代数量增加（ ）、总胆固醇（ ）、高密度脂蛋白（ ）和低密度脂蛋白胆固醇（ ）有关。无论对任何认知或非认知特征采用何种建模策略，我们在任何特征中均未观察到相互作用的证据。我们推测，先前的阳性发现可能是虚假的，也许是由于对潜在人群结构缺乏适当的控制。
