title: The FMR1 premutation and attention-deficit hyperactivity disorder (ADHD): evidence for a complex inheritance.
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.
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, 615 Michael Street, Atlanta, GA 30322, USA.
authors.forename: Jessica Ezzell
authors.initials: JE
authors.lastname: Hunter
authors.forename: Michael P
authors.initials: MP
authors.lastname: Epstein
authors.forename: Stuart W
authors.initials: SW
authors.lastname: Tinker
authors.forename: Ann
authors.initials: A
authors.lastname: Abramowitz
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Sherman
mesh_terms: D000293:Adolescent; D000328:Adult; D000465:Algorithms; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics* / Q000523:psychology; D004522:Educational Status; D005190:Family; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D016014:Linear Models; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D018570:Risk Assessment; D012959:Socioeconomic Factors; D011795:Surveys and Questionnaires; D055815:Young Adult
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human
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