Genomewide survey of panic disorder.

We completed a genome scan of 23 multiplex families of panic disorder. Ninety family members had DSM-III-R panic disorder, and another 23 had recurrent, spontaneous panic attacks that did not satisfy these criteria. We typed 469 markers from the CHLC map (ver 8c7) with an average intermarker distance of 10.3 cM. Two-point lod scores were calculated with both a dominant and a recessive model, and maps of lod scores < -2.00, assuming genetic homogeneity, were constructed by using DSM-III-R panic disorder as the affected phenotype. Lod scores were < -2.00 over 94-95% of the genome. The greatest lod score was 2.23 (theta = 0.15) at the D7S2846 locus, located at 57.8 cM on chromosome 7 according to the Marshfield Clinic map. Flanking markers analyzed in a nonparametric, multipoint analysis using GENEHUNTER resulted in an NPL score of 2.97 at 63 cM on the Marshfield map. This region lies within 15 cM from the D7S435 locus, where Knowles et al. [1998] obtained a lod score of 1.71 (theta = 0.10) for panic disorder (now 2.45 with the addition of new families; James Knowles, personal communication). Thus, the maximum evidence of linkage from two genome scans of panic disorder lies within a small region of chromosome 7p.