SMITH, T. F., Anastopoulos, A. D., Garrett, M. E.,, Arias-Vasquez, A., Franke, B., Oades, R. D., Sonuga-Barke, E. J. S., Asherson, P., Gill, M., Buitelaar, J. K., Sergeant, J. A., Kollins, S. H., Faraone, S. V., Ashley-Koch, A. and the IMAGE Consortium.,

Angiogenic, neurotrophic, and inflammatory system SNPs moderate the association between birth weight and ADHD symptom severity.

American Journal of Medical Genetics B Neuropsychiatric Genetics, 165, 691-704.(request a copy)

Introduction: Low birth weight is associated with increased risk for Attention-Deficit/Hyperactivity Disorder (ADHD); however, the etiological underpinnings of this relationship remain unclear.

Method: 1/ This study investigated if genetic variants in angiogenic, dopaminergic, neurotrophic, kynurenine, and cytokine-related biological pathways moderate the relationship between birth weight and ADHD symptom severity.

2/ A total of 398 youth from two multi-site, family-based studies of ADHD were included in the analysis. The sample consisted of 360 ADHD probands, 21 affected siblings, and 17 unaffected siblings.

3/ A set of 164 SNPs from 31 candidate genes, representing 5 biological pathways, were included in our analyses. Birth weight and gestational age data were collected from a state birth registry, medical records, and parent report. Generalized Estimating Equations tested for main effects and interactions between individual SNPs and birth weight centile in predicting ADHD symptom severity.


1/ SNPs within neurotrophic (NTRK3) and cytokine genes (CNTFR) were associated with ADHD inattentive symptom severity.

2/ There was no main effect of birth weight centile on ADHD symptom severity.

3/ SNPs within angiogenic (NRP1 & NRP2), neurotrophic (NTRK1 & NTRK3), cytokine (IL16 & S100B), and kynurenine (CCBL1 & CCBL2) genes moderate the association between birth weight centile and ADHD symptom severity.

4/ The SNP main effects and SNP?×?birth weight centile interactions remained significant after adjusting for multiple testing.


Genetic variability in angiogenic, neurotrophic, and inflammatory systems may moderate the association between restricted prenatal growth, a proxy for an adverse prenatal environment, and risk to develop ADHD.