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Prenatal Methylmercury Exposure and Genetic Predisposition to Cognitive Deficit at Age 8 Years

Julvez, Jordia,b; Smith, George Daveyc; Golding, Jeand; Ring, Susane; St. Pourcain, Beatec; Gonzalez, Juan Ramonb; Grandjean, Philippea,f

doi: 10.1097/EDE.0b013e31829d5c93

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.

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From the aDepartment of Environmental Health, Harvard School of Public Health, Boston, MA; bCentre for Research in Environmental Epidemiology, Barcelona, Catalonia, Spain; cMRC Integrative Epidemiology Unit (IEU), University of Bristol, Bristol, United Kingdom; dCentre for Child and Adolescent Health, University of Bristol, Bristol, United Kingdom; eSchool of Social and Community Medicine, University of Bristol, Bristol, United Kingdom; and fDepartment of Environmental Medicine, University of Southern Denmark, Odense, Denmark.

Supported by grants from the UK Medical Research Council, the Wellcome Trust (Grant ref: 092731), and the University of Bristol currently provide core support for ALSPAC. The present work was supported by the US National Institute of Environmental Health Sciences (ES09797) and by “Comissionat per a Universitats i Recerca del Departament d’Innovació, Universitats i Empresa de la Generalitat de Catalunya.” This publication is the work of the authors, of whom J.J. and S.R. will serve as guarantors for the contents of this article. The contents of this article are solely the responsibility of the authors and do not represent the views of the ALSPAC executive or the official views of the NIEHS, NIH, or any other funding agency. G.D.S. works in a Unit that receives funding from the UK MRC (G0600705) and the University of Bristol. Funding from the European Research Council grant DEVHEALTH (269874) also supports G.D.S.’ work.

The authors report no conflicts of interest.

Supplemental digital content is available through direct URL citations in the HTML and PDF versions of this article ( This content is not peer-reviewed or copy-edited; it is the sole responsibility of the author.

Correspondence: Jordi Julvez, Centre for Research in Environmental Epidemiology - IMIM, C. Doctor Aiguader 88, 08003 Barcelona, Spain. E-mail:

Received September 27, 2012

Accepted May 23, 2013

© 2013 by Lippincott Williams & Wilkins, Inc