Suggestive evidence for linkage of ADHD features in bipolar disorder to chromosome 10p14.

Higher rates of bipolar disorder amongst the first-degree relatives of probands with ADHD, and increased rates of ADHD in the relatives of bipolar probands have been reported in many studies. This suggests some commonality in the genetic basis for bipolar disorder and ADHD. We hypothesized that ADHD symptoms in bipolar disorder may access a quantitative subphenotype that is genetically less complex and therefore advantageous for mapping studies. The Wender Utah Rating Scale (WURS) was used to quantify ADHD features in 57 bipolar families collected for linkage studies. The factor structure of the WURS was first examined, and heritability was estimated. Linkage analysis was then conducted using the WURS total score and factor scores as quantitative traits. Three factors were identified: impulsivity and defiant behavior, mood instability and anxiety, and inattention. The total WURS and factor scores were each significantly heritable (0.34 <h(2r) < 0.49) in bipolar families. The inattention factor obtained maximum evidence of linkage on chromosome 10p14 (LOD = 3.35, 25 cM). A LOD score of 2.06 for the total WURS score was found on chromosome 12q24 region. Childhood ADHD features in patients with bipolar disorder are heritable and may represent a genetically distinct dimension of illness. 10p14, in particular may contain a locus for inattention in bipolar disorder. Quantitative dimensional phenotypes such as this may be useful for both mapping of genes and understanding the role of genes in bipolar disorder. (c) 2009 Wiley-Liss, Inc.