Variation in an Iron Metabolism Gene Moderates the Association Between Blood Lead Levels and Attention-Deficit/Hyperactivity Disorder in Children

Joel Nigg, Alexis L. Elmore, Neil Natarajan, Karen H. Friderici, Molly A. Nikolas

Research output: Contribution to journalArticle

19 Scopus citations


Although attention-deficit/hyperactivity disorder (ADHD) is a heritable neurodevelopmental condition, there is also considerable scientific and public interest in environmental modulators of its etiology. Exposure to neurotoxins is one potential source of perturbation of neural, and hence psychological, development. Exposure to lead in particular has been widely investigated and is correlated with neurodevelopmental outcomes, including ADHD. To investigate whether this effect is likely to be causal, we used a Mendelian randomization design with a functional gene variant. In a case-control study, we examined the association between ADHD symptoms in children and blood lead level as moderated by variants in the hemochromatosis (HFE) gene. The HFE gene regulates iron uptake and secondarily modulates lead metabolism. Statistical moderation was observed: The magnitude of the association of blood lead with symptoms of ADHD was altered by functional HFE genotype, which is consistent with a causal hypothesis.

Original languageEnglish (US)
Pages (from-to)257-269
Number of pages13
JournalPsychological Science
Issue number2
StatePublished - Feb 1 2016



  • attention
  • childhood development
  • psychopathology

ASJC Scopus subject areas

  • Psychology(all)

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