Analysis of linkage disequilibrium in gamma-aminobutyric acid receptor subunit genes in autistic disorder

Autistic disorder (AD) is a neurodevelopmental disorder characterized by ab normalities in behavior, communication, and social interactions and functio ning. Recently, Cook et al. reported significant linkage disequilibrium wit h an AD susceptibility locus and a marker, GABRB3 155CA-2, in the gamma-ami nobutyric acid(A) (GABA(A)) receptor ps-subunit gene on chromosome 15q11-q1 3, This linkage disequilibrium was detected using a multiallelic version of the transmission/disequilibrium test (TDT) in a sample of nuclear families having at least one child with autistic disorder. In an attempt to replica te this finding we tested for linkage disequilibrium with this marker, as w ell as with three additional markers in and around the GABA(A) receptor bet a(3)-subunit gene, in an independent, clinically comparable set of AD famil ies. Unlike Cook et al,, we failed to detect significant linkage disequilib rium between GABRB3 155CA-2 and AD in our sample. We did, however, find sug gestive evidence for linkage disequilibrium with a marker, GABRB3, approxim ately 60 kb beyond the 3' end of beta 3-subunit gene. This finding lends su pport for previous reports implicating the involvement of genes in this reg ion with AD. Am, J, Med. Genet, (Neuropsychiatr. Genet,) 96:43-48, 2000 (C) 2000 Wiley-Liss, Inc.