title: Variation in an Iron Metabolism Gene Moderates the Association Between Blood Lead Levels and Attention-Deficit/Hyperactivity Disorder in Children.
abstract: 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.
authors.affiliation: Department of Psychiatry, Oregon Health & Science University Department of Behavioral Neuroscience, Oregon Health & Science University niggj@ohsu.edu.
authors.forename: Joel T
authors.initials: JT
authors.lastname: Nigg
authors.affiliation: Department of Psychological & Brain Sciences, University of Iowa.
authors.forename: Alexis L
authors.initials: AL
authors.lastname: Elmore
authors.affiliation: Department of Psychiatry, Oregon Health & Science University.
authors.forename: Neil
authors.initials: N
authors.lastname: Natarajan
authors.affiliation: Department of Microbiology and Molecular Genetics, Michigan State University.
authors.forename: Karen H
authors.initials: KH
authors.lastname: Friderici
authors.affiliation: Department of Microbiology and Molecular Genetics, Michigan State University.
authors.forename: Molly A
authors.initials: MA
authors.lastname: Nikolas
mesh_terms: D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000097:blood* / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D000071020:Hemochromatosis Protein / Q000235:genetics*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007854:Lead / Q000097:blood*; D007855:Lead Poisoning / Q000097:blood / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide; D054928:Validation Studies as Topic
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D007854:Lead; D007501:Iron
keywords: attention; childhood development; psychopathology