A third-pass genome scan in panic disorder: evidence for multiple susceptibility loci.
BACKGROUND
Panic disorder (PD) is a common illness with a definite but "complex" genetic contribution and estimated heritability of 30-46%.


METHODS
We report a genome scan in 120 multiplex PD pedigrees consisting of 1591 individuals of whom 992 were genotyped with 371 markers at an average spacing of 9cM. Parametric two-point, multipoint, and nonparametric analyses were performed using three PD models (Broad, Intermediate, Narrow) and allowing for homogeneity or heterogeneity. The two-point analyses were also performed allowing for independent male and female recombination fractions (theta). Genome-wide significance was empirically evaluated using simulations of this dataset.


RESULTS
Evidence for linkage reached genome-wide significance in one region on chromosome 15q (near GABA-A receptor subunit genes) and was suggestive at loci on 2p, 2q and 9p using an averaged theta. Analyses allowing for sex-specific theta's were consistent except that support at one locus on 2q increased to genome-wide significance and an additional region of suggestive linkage on 12q was identified. However, differences in male and female recombination fractions predicted by the sex-specific approach were not consistent with current physical maps.


CONCLUSIONS
These data provide evidence for chromosomal regions on 15q and 2q that may be important in genetic susceptibility to panic disorder. Although we are encouraged by the findings of analyses using sex-specific recombination fractions, we also note that further understanding of this analytic strategy will be important.
Fyer
Abby J
AJ
Department of Psychiatry, College of Physicians and Surgeons, Columbia University and New York State Psychiatric Institute, New York, New York 10032, USA. ajfyer@pi.cpmc.columbia.edu
Hamilton
Steven P
SP
Durner
Martina
M
Haghighi
Fatemeh
F
Heiman
Gary A
GA
Costa
Ramiro
R
Evgrafov
Oleg
O
Adams
Philip
P
de Leon
Ada Baisre
AB
Taveras
Nilda
N
Klein
Donald F
DF
Hodge
Susan E
SE
Weissman
Myrna M
MM
Knowles
James A
JA
D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D023281:Genomics; D006801:Humans; D008126:Lod Score; D008297:Male; D008957:Models, Genetic; D016584:Panic Disorder / Q000235:genetics*; D010375:Pedigree; D012737:Sex Factors