Linkage genome scan for loci predisposing to panic disorder or agoraphobia

We conducted a 10 cM linkage genome scan in a set of 20 American pedigrees (153 subjects), ascertained through probands with panic disorder (PD). Several anxiety disorders segregate in these families; they were diagnosed on the basis of Schedule for Affective Disorders and Schizophrenia interview. In this article, we describe results for panic disorder and agoraphobia, which are closely related, common, heritable anxiety disorders. This is the first complete linkage genome scan for agoraphobia and the third for PD. A total of 407 markers (389 autosomal, 18 X chromosome) were genotyped. Multipoint LOD score and NPL analysis were completed using GENEHUNTER2. For PD, two genomic regions meet criteria for suggestive linkage. One of these regions is on chromosome 1 (LOD score=2.04). This region coincides with a region that generated a LOD score of 1.1 in a previous genome scan by Crowe et al. [2001: Am J Med Genet (Neuropsychiatr Genet) 105:105-109]. The other (LOD score=2.01) is located on chromosome 11p and occurs at marker CCKBR, one of eight candidate genes examined. For agoraphobia, the most promising potential linkage was on chromosome 3 (NPL score = 2.75; P = 0.005). This was accounted for primarily by a single family that by itself generated an NPL score of 10.01 (P = 0.0039) and a LOD score of 2.10. These results provide initial evidence for a genetic locus on chromosome 3 that contributes to risk for agoraphobia. They also support suggestive linkage to two risk loci for panic disorder. Additional potential loci were identified with lesser statistical support; several of these were consistent with previously reported panic disorder linkage results. Overall, the results presented here suggest that PD and agoraphobia are complex traits that share some, but not all, of their susceptibility loci. Published 2001 Wiley-Liss, Inc(dagger).