Association of the GABRD gene and childhood-onset mood disorders.
The chromosome 1p36 region was previously indicated as a locus for susceptibility to recurrent major depressive disorder based on a linkage study in a sample of 497 sib pairs. We investigated the gamma-aminobutyric acid A (GABA(A)) delta receptor subunit gene, GABRD, as a susceptibility gene to childhood-onset mood disorders (COMD) because of substantial evidence implicating GABAergic dysfunction in mood disorders and the position of this gene near the 1p36 linkage region. Using a sample consisting of 645 Hungarian families with a child/adolescent proband diagnosed with a mood disorder with the onset of the first episode before age 15, we found some evidence for the association of two polymorphisms located within the gene, rs2376805 and rs2376803, as well as significant evidence for biased transmission of the haplotypes of these two markers (global chi(2) test for haplotypes = 12.746, 3 df, P = 0.0052). Furthermore, significant evidence of association was only observed in male subjects (n = 438) when the results were analyzed by sex (chi(2) = 9.000 1 df, P = 0.003 for rs2376805). This was in contrast with the previous linkage findings, as LOD scores exceeding 3 were only in female-female pairs in that study. These findings point to the GABRD gene as a susceptibility gene for COMD; however, this gene may not explain the previous linkage finding.
Feng
Y
Y
Genetics and Development Division, Toronto Western Research Institute, University Health Network, Toronto, Ontario, Canada.
Kapornai
K
K
Kiss
E
E
Tamás
Z
Z
Mayer
L
L
Baji
I
I
Daróczi
G
G
Benák
I
I
Kothencné
V O
VO
Dombovári
E
E
Kaczvinszk
E
E
Besnyo
M
M
Gádoros
J
J
Székely
J
J
Kovacs
M
M
Vetró
A
A
Kennedy
J L
JL
Barr
C L
CL
D000293:Adolescent; D017668:Age of Onset; D005260:Female; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D006814:Hungary / Q000453:epidemiology; D015810:Linkage Disequilibrium / Q000235:genetics*; D008297:Male; D019964:Mood Disorders / Q000453:epidemiology / Q000235:genetics*; D009679:Nuclear Family; D020641:Polymorphism, Single Nucleotide; D011963:Receptors, GABA-A / Q000235:genetics*; D012737:Sex Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
C464500:GABRD protein, human; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid