Association between a GABRB3 polymorphism and autism.
Autistic disorder (OMIM 209850) is a disease with a significant genetic component of a complex nature.(1) Cytogenetic abnormalities in the Prader-Willi/Angelman syndrome critical region (15q11-13) have been described in several individuals with autism.(1) For this reason, markers across this region have been screened for evidence of linkage and association, and a marker (155CA-2) in the gamma-aminobutyric acid type-A receptor beta3 subunit gene (GABRB3) has been associated in one study(2) but not others.(3-5) We completed an association analysis with 155CA-2 using the transmission disequilibrium test (TDT) in a set of 80 autism families (59 multiplex and 21 trios). We also used four additional markers (69CA, 155CA-1, 85CA, and A55CA-1) localized within 150 kb of 155CA-2. The use of multi-allelic TDT (MTDT) (P < 0.002), as well as the TDT (P < 0.004), demonstrated an association between autistic disorder and 155CA-2 in these families. Meiotic segregation distortion could be excluded as a possible cause for these results since no disequilibrium was observed in unaffected siblings. These findings support a role for genetic variants within the GABA receptor gene complex in 15q11-13 in autistic disorder.
Buxbaum
J D
JD
Laboratory of Molecular Neuropsychiatry, Mount Sinai School of Medicine, New York, NY 10029, USA.
Silverman
J M
JM
Smith
C J
CJ
Greenberg
D A
DA
Kilifarski
M
M
Reichert
J
J
Cook
E H
EH
Fang
Y
Y
Song
C-Y
CY
Vitale
R
R
D001321:Autistic Disorder / Q000235:genetics*; D002874:Chromosome Mapping; D002884:Chromosomes, Human, Pair 15; D005190:Family; D005260:Female; D005819:Genetic Markers; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D011963:Receptors, GABA-A / Q000235:genetics*
D005819:Genetic Markers; D011963:Receptors, GABA-A