Abstract
We recently reported elevated symptoms associated with attention-deficit hyperactivity disorder (ADHD) among adult female carriers of the FMR1 premutation. To gain insight into the contribution of this mutation in the context of polygenes, we examined the proportion of variation in these symptoms due to residual genetic factors after adjustment for the effect of the premutation. To accomplish this, we performed a familial aggregation analysis of ADHD symptoms among 231 females from 82 pedigrees using scores from the Connors Adult ADHD Rating Scales. Results indicate that after accounting for the effect of FMR1, there are significant residual polygenic effects on self-reported symptoms of ADHD, as measured by the ADHD Index (p = 0.0117) and problems with self-concept (p = 0.0110), one specific symptom domain associated with ADHD. For both measures, FMR1 accounts for ~5% of the variance while polygenes account for ~50% of the residual variance, suggesting that the premutation acts in concert with additional genetic loci to influence the severity of ADHD symptoms.
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Acknowledgments
We would like to thank the women who took the time and effort to participate in this study. We also thank the members of the Fragile X Research Team for their help in conducting this project. This work was supported by the National Institutes of Health grants R01 HD29909, P30 HD24064, and HG003618.
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Edited by Deborah Finkel.
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Hunter, J.E., Epstein, M.P., Tinker, S.W. et al. The FMR1 Premutation and Attention-Deficit Hyperactivity Disorder (ADHD): Evidence for a Complex Inheritance. Behav Genet 42, 415–422 (2012). https://doi.org/10.1007/s10519-011-9520-z
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DOI: https://doi.org/10.1007/s10519-011-9520-z