title: 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.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK. C.Bonilla@bristol.ac.uk
authors.forename: Carolina
authors.initials: C
authors.lastname: Bonilla
authors.forename: Debbie A
authors.initials: DA
authors.lastname: Lawlor
authors.forename: Yoav
authors.initials: Y
authors.lastname: Ben-Shlomo
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Ness
authors.forename: David
authors.initials: D
authors.lastname: Gunnell
authors.forename: Susan M
authors.initials: SM
authors.lastname: Ring
authors.forename: George Davey
authors.initials: GD
authors.lastname: Smith
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Lewis
mesh_terms: D001786:Blood Glucose / Q000235:genetics*; D002648:Child; D003072:Cognition Disorders / Q000097:blood / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics*; D005215:Fasting / Q000502:physiology; D005260:Female; D005333:Fetus / Q000187:drug effects*; D014644:Genetic Variation / Q000502:physiology*; D006801:Humans; D007360:Intelligence; D008137:Longitudinal Studies; D010290:Parents / Q000523:psychology; D011247:Pregnancy; D011446:Prospective Studies; D018570:Risk Assessment
chemical_list: D001786:Blood Glucose