A Birth Cohort Study about the Genetic Modification of Prenatal Methylmercury Association with Child Cognitive Development

Abstract

Abstract Genetic predisposition may 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 (ALSPAC, 1991-2000), Bristol, United Kingdom. A subgroup (n = 1127 from a pilot study and 1045 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), as well as the Wechsler Intelligence Scale for Children Intelligence Quotient (IQ) scores. Log10-transformed mercury concentration was positively associated with IQ, but adjustment confounding cofactors attenuated this association. Enhanced interaction with methylmercury was replicated in the new study for the minor allele of rs1042838 (progesterone receptor) (Beta; 95% Confidence Interval) = (-11.8; -23.0, -0.6) (P-for-interaction = 0.004) and weakly for rs662 (paraoxonase 1) (-3.6; -11.4, 4.3) (P = 0.117). In the joint sample, new interacting single-nucleotide polymorphisms (SNPs) 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.