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 - 1. Oct 2019

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Cohort Studies
Mercury
Progesterone Receptors
Single Nucleotide Polymorphism
Alleles
Confidence Intervals
Aryldialkylphosphatase
Wechsler Scales
Metallothionein
Cognition
Longitudinal Studies
Joints
Parents

Keywords

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

Cite this

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title = "A Birth Cohort Study on the Genetic Modification of the Association of Prenatal Methylmercury With Child Cognitive Development",
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.",
keywords = "ALSPAC, SNPs, cognitive functions, genes, mercury, neuropsychological development, population-based birth cohort, pregnancy",
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A Birth Cohort Study on the Genetic Modification of the Association of Prenatal Methylmercury With Child Cognitive Development. / Julvez, Jordi; Smith, George Davey; Ring, Susan M; Grandjean, Philippe.

In: American Journal of Epidemiology, Vol. 188, No. 10, 01.10.2019, p. 1784-1793.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - A Birth Cohort Study on the Genetic Modification of the Association of Prenatal Methylmercury With Child Cognitive Development

AU - Julvez, Jordi

AU - Smith, George Davey

AU - Ring, Susan M

AU - Grandjean, Philippe

PY - 2019/10/1

Y1 - 2019/10/1

N2 - 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.

AB - 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.

KW - ALSPAC

KW - SNPs

KW - cognitive functions

KW - genes

KW - mercury

KW - neuropsychological development

KW - population-based birth cohort

KW - pregnancy

U2 - 10.1093/aje/kwz156

DO - 10.1093/aje/kwz156

M3 - Journal article

VL - 188

SP - 1784

EP - 1793

JO - American Journal of Epidemiology

JF - American Journal of Epidemiology

SN - 0002-9262

IS - 10

ER -