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Association of dopamine transporter gene variants with childhood ADHD features in bipolar disorder
Author(s) -
Greenwood Tiffany A.,
Joo EunJeong,
Shekhtman Tatyana,
Sadovnick A. Dessa,
Remick Ronald A.,
Keck Paul E.,
McElroy Susan L.,
Kelsoe John R.
Publication year - 2013
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.32108
Subject(s) - impulsivity , bipolar disorder , dopamine transporter , mood disorders , snp , attention deficit hyperactivity disorder , psychology , mood , single nucleotide polymorphism , clinical psychology , psychiatry , dopamine , medicine , genetics , gene , biology , genotype , neuroscience , anxiety , dopaminergic
Abstract Bipolar disorder (BD) and attention deficit hyperactivity disorder (ADHD) exhibit remarkably high rates of comorbidity, as well as patterns of familial co‐segregation. Epidemiological data suggests that these disorders either share a common genetic architecture or that ADHD features in BD may represent an etiologically distinct subtype. We previously used the Wender Utah Rating Scale (WURS) to assess ADHD features in BD families and identified three heritable factors relating to impulsivity, mood instability, and inattention. Linkage analysis revealed a LOD score of 1.33 for the inattention factor on 5p15.3 near the dopamine transporter gene ( DAT1 ), which has been associated with both BD and ADHD. Pharmacological evidence also suggests a role for DAT in both disorders. We have now evaluated the association of ten DAT1 variants for the WURS total score and factors in an overlapping sample of 87 BD families. Significant associations for three SNPs were observed across the WURS measures, notably for a SNP in intron 8 with the WURS total score ( P = 0.007) and for variants in introns 9 and 13 with mood instability ( P = 0.009 and 0.004, respectively). Analysis of an independent sample of 52 BD cases and 46 healthy controls further supported association of the intron 8 variant with mood instability ( P = 0.005), and a combined analysis confirmed the associations of this SNP with WURS total score. Impulsivity and mood instability ( P = 0.002, 0.007, and 8 × 10 −4 , respectively). These data suggest that variants within DAT1 may predispose to a subtype of BD characterized by early prodromal features that include attentional deficits. © 2012 Wiley Periodicals, Inc.