The FMR1 premutation and attention-deficit hyperactivity disorder (ADHD): evidence for a complex inheritance

Behav Genet. 2012 May;42(3):415-22. doi: 10.1007/s10519-011-9520-z. Epub 2011 Nov 19.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Algorithms
  • Attention Deficit Disorder with Hyperactivity / genetics*
  • Attention Deficit Disorder with Hyperactivity / psychology
  • Educational Status
  • Family
  • Female
  • Fragile X Mental Retardation Protein / genetics*
  • Heterozygote
  • Humans
  • Linear Models
  • Middle Aged
  • Mutation / genetics
  • Risk Assessment
  • Socioeconomic Factors
  • Surveys and Questionnaires
  • Young Adult

Substances

  • FMR1 protein, human
  • Fragile X Mental Retardation Protein