Association and linkage studies of candidate genes involved in GABAergic neurotransmission in lithium-responsive bipolar disorder
Duffy A., Turecki G., Grof P., Cavazzoni P., Grof E., Joober R., Ahrens B., Berghöfer A., Müller-Oerlinghausen B., Dvořáková M., Libigerová E., Vojtěchovský M., Zvolský P., Nilsson A., Licht RW., Rasmussen NA., Schou M., Vestergaard P., Holzinger A., Schumann C., Thau K., Robertson C., Rouleau GA., Alda M.
Objective: To test for genetic linkage and association with GABAergic candidate genes in lithium-responsive bipolar disorder. Design: Polymorphisms located in genes that code for GABRA3, GABRA5 and GABRB3 subunits of the GABAA receptor were investigated using association and linkage strategies. Participants: A total of 138 patients with bipolar I disorder with a clear response to lithium prophylaxis, selected from specialized lithium clinics in Canada and Europe that are part of the International Group for the Study of Lithium-Treated Patients, and 108 psychiatrically healthy controls. Families of 24 probands were suitable for linkage analysis. Outcome measures: The association between the candidate genes and patients with bipolar disorder versus that of controls and genetic linkage within families. Results. There was no significant association or linkage found between lithium-responsive bipolar disorder and the GABAergic candidate genes investigated. Conclusions: This study does not support a major role for the GABAergic candidate genes tested in lithium-responsive bipolar disorder.