Investigation of autism and GABA receptor subunit genes in multiple ethnic groups

Ann L. Collins, Deqiong Ma, Patrice L. Whitehead, Eden R Martin, Harry H. Wright, Ruth K. Abramson, John P. Hussman, Jonathan L. Haines, Michael Cuccaro, John Gilbert, Margaret A Pericak-Vance

Research output: Contribution to journalArticle

93 Citations (Scopus)

Abstract

Autism is a neurodevelopmental disorder of complex genetics, characterized by impairment in social interaction and communication, as well as repetitive behavior. Multiple lines of evidence, including alterations in levels of GABA and GABA receptors in autistic patients, indicate that the GABAergic system, which is responsible for synaptic inhibition in the adult brain, may be involved in autism. Previous studies in our lab indicated association of noncoding single nucleotide polymorphisms (SNPs) within a GABA receptor subunit gene on chromosome 4, GABRA4, and interaction between SNPs in GABRA4 and GABRB1 (also on chromosome 4), within Caucasian autism patients. Studies of genetic variation in African-American autism families are rare. Analysis of 557 Caucasian and an independent population of 54 African-American families with 35 SNPs within GABRB1 and GABRA4 strengthened the evidence for involvement of GABRA4 in autism risk in Caucasians (rs17599165, p=0.0015; rs1912960, p=0.0073; and rs17599416, p=0.0040) and gave evidence of significant association in African-Americans (rs2280073, p=0.0287 and rs16859788, p=0.0253). The GABRA4 and GABRB1 interaction was also confirmed in the Caucasian dataset (most significant pair, rs1912960 and rs2351299; p=0.004). Analysis of the subset of families with a positive history of seizure activity in at least one autism patient revealed no association to GABRA4; however, three SNPs within GABRB1 showed significant allelic association; rs2351299 (p=0.0163), rs4482737 (p=0.0339), and rs3832300 (p=0.0253). These results confirmed our earlier findings, indicating GABRA4 and GABRB1 as genes contributing to autism susceptibility, extending the effect to multiple ethnic groups and suggesting seizures as a stratifying phenotype.

Original languageEnglish
Pages (from-to)167-174
Number of pages8
JournalNeurogenetics
Volume7
Issue number3
DOIs
StatePublished - Jul 1 2006
Externally publishedYes

Fingerprint

GABA Receptors
Autistic Disorder
Ethnic Groups
Single Nucleotide Polymorphism
Genes
African Americans
Chromosomes, Human, Pair 4
Seizures
Interpersonal Relations
gamma-Aminobutyric Acid
Communication
Phenotype
Brain
Population

Keywords

  • Association
  • Autism
  • Ethnicity
  • GABA receptors
  • SNPs

ASJC Scopus subject areas

  • Genetics(clinical)
  • Neuroscience(all)

Cite this

Investigation of autism and GABA receptor subunit genes in multiple ethnic groups. / Collins, Ann L.; Ma, Deqiong; Whitehead, Patrice L.; Martin, Eden R; Wright, Harry H.; Abramson, Ruth K.; Hussman, John P.; Haines, Jonathan L.; Cuccaro, Michael; Gilbert, John; Pericak-Vance, Margaret A.

In: Neurogenetics, Vol. 7, No. 3, 01.07.2006, p. 167-174.

Research output: Contribution to journalArticle

Collins, AL, Ma, D, Whitehead, PL, Martin, ER, Wright, HH, Abramson, RK, Hussman, JP, Haines, JL, Cuccaro, M, Gilbert, J & Pericak-Vance, MA 2006, 'Investigation of autism and GABA receptor subunit genes in multiple ethnic groups', Neurogenetics, vol. 7, no. 3, pp. 167-174. https://doi.org/10.1007/s10048-006-0045-1
Collins, Ann L. ; Ma, Deqiong ; Whitehead, Patrice L. ; Martin, Eden R ; Wright, Harry H. ; Abramson, Ruth K. ; Hussman, John P. ; Haines, Jonathan L. ; Cuccaro, Michael ; Gilbert, John ; Pericak-Vance, Margaret A. / Investigation of autism and GABA receptor subunit genes in multiple ethnic groups. In: Neurogenetics. 2006 ; Vol. 7, No. 3. pp. 167-174.
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