A linkage study between the GABA(A beta 2) and GABA(A gamma 2) subunit genes and major psychoses

Background: Alterations of the gamma-aminobutyric acid (GABA) system have been implicated in the pathophysiology of major psychoses. Objective: Restriction fragment length polymorphisms associated with the human gamma-aminobutyric acid type A (GABA(A)) beta(2) and GABA(A) gamma(2) subunit genes on chromosome 5q32-q35 were tested to determine whether they confer susceptibility to major psychoses. Methods: Thirty-two schizophrenic families and 25 bipolar families were tested for linkage. Results: Nonparametric linkage (NPL) analysis performed by GENEHUNTER showed no significant NPL scores for both genes in schizophrenia (GABA(A) beta2: NPL narrow=-0.450; NPL broad=-0.808; GABA(A) gamma(2): NPL narrow=0.177; NPL broad=-0.051) or bipotar disorder (GABA(A) beta(2): NPL narrow=0.834; NPL broad=0.783; GABA(A) gamma(2): NPL narrow=-0.159; NPL broad=0.070). Conclusion: Linkage analysis does not support the hypothesis that variants within the GABA(A) beta(2) and GABA(A) gamma(2) genes are significantly linked to major psychoses in a Portuguese population.