Premium
A DRD1 haplotype is associated with risk for autism spectrum disorders in male‐only affected sib‐pair families
Author(s) -
Hettinger Joe A.,
Liu Xudong,
Schwartz Charles E.,
Michaelis Ron C.,
Holden Jeanette J.A.
Publication year - 2008
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.30655
Subject(s) - haplotype , autism , genetics , biology , allele , genotype , dopaminergic , locus (genetics) , psychology , gene , developmental psychology , neuroscience , dopamine
Individuals with autism spectrum disorders (ASDs) have impairments in executive function and social cognition, with males generally being more severely affected in these areas than females. Because the dopamine D1 receptor (encoded by DRD1) is integral to the neural circuitry mediating these processes, we examined the DRD1 gene for its role in susceptibility to ASDs by performing single marker and haplotype case–control comparisons, family‐based association tests, and genotype–phenotype assessments (quantitative transmission disequilibrium tests: QTDT) using three DRD1 polymorphisms, rs265981C/T, rs4532A/G, and rs686T/C. Our previous findings suggested that the dopaminergic system may be more integrally involved in families with affected males only than in other families. We therefore restricted our study to families with two or more affected males (N = 112). There was over‐transmission of rs265981‐C and rs4532‐A in these families ( P = 0.040, P = 0.038), with haplotype TDT analysis showing over‐transmission of the C‐A‐T haplotype ( P = 0.022) from mothers to affected sons ( P = 0.013). In addition, haplotype case–control comparisons revealed an increase of this putative risk haplotype in affected individuals relative to a comparison group ( P = 0.004). QTDT analyses showed associations of the rs265981‐C, rs4532‐A, rs686‐T alleles, and the C‐A‐T haplotype with more severe problems in social interaction, greater difficulties with nonverbal communication and increased stereotypies compared to individuals with other haplotypes. Preferential haplotype transmission of markers at the DRD1 locus and an increased frequency of a specific haplotype support the DRD1 gene as a risk gene for core symptoms of ASD in families having only affected males. © 2008 Wiley‐Liss, Inc.