title: Prenatal methylmercury exposure and genetic predisposition to cognitive deficit at age 8 years.
abstract: BACKGROUND
  Cognitive consequences at school age associated with prenatal methylmercury (MeHg) exposure may need to take into account nutritional and sociodemographic cofactors as well as relevant genetic polymorphisms.
  
  
  METHODS
  A subsample (n = 1,311) of the Avon Longitudinal Study of Parents and Children (Bristol, UK) was selected, and mercury (Hg) concentrations were measured in freeze-dried umbilical cord tissue as a measure of MeHg exposure. A total of 1135 children had available data on 247 single-nucleotide polymorphisms (SNPs) within relevant genes, as well as the Wechsler Intelligence Scale for Children Intelligence Quotient (IQ) scores at age 8 years. Multivariate regression models were used to assess the associations between MeHg exposure and IQ and to determine possible gene-environment interactions.
  
  
  RESULTS
  Hg concentrations indicated low background exposures (mean = 26 ng/g, standard deviation = 13). Log10-transformed Hg was positively associated with IQ, which attenuated after adjustment for nutritional and sociodemographic cofactors. In stratified analyses, a reverse association was found in higher social class families (for performance IQ, P value for interaction = 0.0013) among whom there was a wider range of MeHg exposure. Among 40 SNPs showing nominally significant main effects, MeHg interactions were detected for rs662 (paraoxonase 1) and rs1042838 (progesterone receptor) (P < 0.05) and for rs3811647 (transferrin) and rs2049046 (brain-derived neurotrophic factor) (P < 0.10).
  
  
  CONCLUSIONS
  In this population with a low level of MeHg exposure, there were only equivocal associations between MeHg exposure and adverse neuropsychological outcomes. Heterogeneities in several relevant genes suggest possible genetic predisposition to MeHg neurotoxicity in a substantial proportion of the population. Future studies need to address this possibility.
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Boston, MA, USA.
authors.forename: Jordi
authors.initials: J
authors.lastname: Julvez
authors.forename: George Davey
authors.initials: GD
authors.lastname: Smith
authors.forename: Jean
authors.initials: J
authors.lastname: Golding
authors.forename: Susan
authors.initials: S
authors.lastname: Ring
authors.forename: Beate St
authors.initials: BS
authors.lastname: Pourcain
authors.forename: Juan Ramon
authors.initials: JR
authors.lastname: Gonzalez
authors.forename: Philippe
authors.initials: P
authors.lastname: Grandjean
mesh_terms: D002648:Child; D003072:Cognition Disorders / Q000235:genetics*; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008767:Methylmercury Compounds / Q000633:toxicity*; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology*; D012044:Regression Analysis; D006113:United Kingdom / Q000453:epidemiology; D014888:Wechsler Scales
chemical_list: D008767:Methylmercury Compounds
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