A Birth Cohort Study on the Genetic Modification of the Association of Prenatal Methylmercury With Child Cognitive Development

Jordi Julvez, George Davey Smith, Susan M Ring, Philippe Grandjean

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Abstract

Genetic predisposition might affect neurodevelopmental outcomes of prenatal methylmercury exposure. We examined suspected heterogeneities for modification of exposure-related neurodevelopment in children from the Avon Longitudinal Study of Parents and Children (1991-2000), Bristol, United Kingdom. A subgroup (n = 1,127 from a pilot study and 1,045 from the present study) was identified based on the availability of the mercury concentration of cord tissue as a measure of prenatal methylmercury exposure, data on 247 single-nucleotide polymorphisms (SNPs), and Wechsler Intelligence Scale for Children intelligence quotient (IQ) scores. Log10-transformed mercury concentration was positively associated with IQ, but adjustment for confounding cofactors attenuated this association. A finding of enhanced interaction with methylmercury was replicated in this study for the minor allele of rs1042838 (progesterone receptor) (β = -11.8, 95% confidence interval: -23.0, -0.6; P for interaction = 0.004) and weakly for rs662 (paraoxonase 1) (β = -3.6, 95% confidence interval: -11.4, 4.3; P = 0.117). In the joint sample, new interacting single-nucleotide polymorphisms were discovered in relation to superoxide dismutase 2, ATP binding cassette subfamily A member 1, and metallothionein 1M genes. While the low-level prenatal exposure to methylmercury was not associated with child cognition, progesterone receptor rs1042838 minor alleles revealed a negative association of mercury exposure with IQ.

Original languageEnglish
JournalAmerican Journal of Epidemiology
Volume188
Issue number10
Pages (from-to)1784-1793
ISSN0002-9262
DOIs
Publication statusPublished - Oct 2019

Keywords

  • ALSPAC
  • SNPs
  • cognitive functions
  • genes
  • mercury
  • neuropsychological development
  • population-based birth cohort
  • pregnancy

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