Multivariate analysis of anxiety disorders yields further evidence of linkage to chromosomes 4q21 and 7p in panic disorder families.

Replication has been difficult to achieve in linkage studies of psychiatric disease. Linkage studies of panic disorder have indicated regions of interest on chromosomes 1q, 2p, 2q, 3, 7, 9, 11, 12q13, 12q23, and 15. Few regions have been implicated in more than one study. We examine two samples, the Iowa (IA) and the Columba panic disorder families. We use the fuzzy-clustering method presented by Kaabi et al. [Kaabi et al. (2006); Am J Hum Genet 78: 543-553] to summarize liability to panic disorder, agoraphobia, simple phobia, and social phobia. Kaabi et al. applied this method to the Yale panic disorder linkage families and found evidence of linkage to chromosomes 4q21, 4q32, 7p, and 8. When we apply the same method to the IA families, we obtain overlapping evidence of linkage to chromosomes 4q21 and 7p. Additionally, we find evidence of linkage on chromosomes 1, 5, 6, 16, and 22. The Columbia (CO) data does not indicate linkage to any of the Kaabi et al. peaks, instead implicating chromosomes 2 and 22q11 (2 Mb from COMT). There is some evidence of overlapping linkage between the IA and CO datasets on chromosomes 1 and 14. While use of fuzzy clustering has not produced complete concordance across datasets, it has produced more than previously seen in analyses of panic disorder proper. We conclude that chromosomes 4q21 and 7p should be considered strong candidate regions for panic and fear-associated anxiety disorder loci. More generally, this suggests that analyses including multiple aspects of psychopathology may lead to greater consistency across datasets.

Evidence of overlapping genetic diathesis of panic attacks and gastrointestinal disorders in a sample of male twin pairs.

We explored the comorbidity between panic attacks (PA), whose symptoms can include gastrointestinal discomfort, and gastrointestinal disorders (GD). Structural equation modeling was used to analyze data from 1,874 MZ and 1,498 DZ male-male twin pairs from the Vietnam Era Twin Registry. PA and GD were associated (relative risk for GD = 2). The percentage of liability due to genetic factors was estimated to be 37% for PA and 31% for GD. There was significant correlation between the genetic risk factors for PA and GD (estimated r = .55, 95% CI of 34% to 82%) and no evidence of correlation between the environmental causes of PA and GD. Therefore, PA and GD comorbidity can be explained by overlapping genetic factors and not overlapping environmental factors. Although these data cannot identify a biological pathway for such a shared liability, it suggests the presence of GD may be informative for genetic studies of panic.