Maternal and offspring fasting glucose and type 2 diabetes-associated genetic variants and cognitive function at age 8: a Mendelian randomization study in the Avon Longitudinal Study of Parents and Children

BMC Medical Genetics

Research Article

Andrew R Ness¹  David Gunnell²  Yoav Ben–Shlomo²  Carolina Bonilla²  Susan M Ring²  Sarah J Lewis²  Debbie A Lawlor³  George Davey Smith³ 

[1] School of Oral and Dental Sciences, University of Bristol, Bristol, UK;School of Social and Community Medicine, University of Bristol, BS8 2BN, Bristol, UK;School of Social and Community Medicine, University of Bristol, BS8 2BN, Bristol, UK;MRC Centre for Causal Analyses in Translational Epidemiology, School of Social and Community Medicine, University of Bristol, Bristol, UK;

关键词: Mendelian randomization;    Fasting glucose;    Type 2 diabetes;    IQ;    ALSPAC;   

DOI  :  10.1186/1471-2350-13-90

 received in 2012-02-16, accepted in 2012-09-20,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundIn 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.MethodsIn 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.ResultsWe 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.ConclusionsMaternal 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.

【 授权许可】

CC BY   
© Bonilla et al.; licensee BioMed Central Ltd. 2012