Journal of the American Academy of Child & Adolescent Psychiatry
ReviewMeasured Gene-by-Environment Interaction in Relation to Attention-Deficit/Hyperactivity Disorder
Section snippets
General Methodologic Issues in G×E
Methodologic issues in G×E research have been frequently reviewed and are readily available to interested readers.1, 2, 3, 6, 7 Therefore, we only briefly note particularly salient methodologic issues that directly affect our ability to interpret the existing ADHD literature.
An overarching issue is the substantial danger of false-positive findings. One rather neglected issue involves measurement or statistical artifacts. Under some conditions (depending on allele frequency and on measurement
Etiologic Structure
ADHD differs from depression and externalizing behaviors in regard to its etiologic structure. Depression, conduct disorder, and oppositional defiant disorder tend to show a pattern of moderate heritability, with small-to-moderate shared (or common) environment effects.14, 15 ADHD, in contrast, has higher heritability with small nonshared environment effects and null shared environment effects,15, 16 although it remains possible that shared environment effects are masked by rater contrast
Approach to the Current Literature and Selection of Studies
The methodologic approach to this review was as follows. Literature searches were conducted in MEDLINE using “gene by environment,” “G×E,” “ADHD,” and “externalizing.” Reference sections of recent publications were also scanned. Researchers in the field were contacted to inquire about missed or in-press papers, including announcements to all researchers participating in the International ADHD Molecular Genetics Network.38 Studies identified were then examined to determine if they constituted an
Discussion
The resulting studies identified are summarized in Table 3.39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54 It summarizes 16 studies that examined ADHD as an outcome. Although several gene markers were examined, only three were examined in multiple studies.
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The DRD4 exon III variable number tandem repeat (a 48-basepair repeat often referred to by the number of repeats, such as the “7 repeat” or “4-repeat” variant) generally yielded negative findings, but did show unreplicated
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This article is discussed in an editorial by Drs. James J. Hudziak and Stephen V. Faraone on page 729 of the August 2010 issue.
This work was supported by NIMHR01 59105.
This article is one of several articles published in the August and September issues of the Journal of the American Academy of Child and Adolescent Psychiatry that explores the intersection of genetics with mental health disorders in children and adolescents. The editors invite the reader to investigate the additional articles on this burgeoning area of developmental psychopathology.
Disclosure: Drs. Nigg and Burt and Ms. Nikolas report no biomedical financial interests or potential conflicts of interest.