Transmission disequilibrium and quantitative analysis of multiloci polymorphisms within the MAOA gene using family trios with antisocial alcoholism

Previous studies have implicated variants of the X-chromosomal monoamine oxidase A gene (MAOA) in antisocial behavior and/or alcoholism. Here, we performed haplotype relative risk (HRR) and transmission disequilibrium (TDT) in 35 family trios with early onset antisocial alcoholic probands with 4 markers within the MaoA gene: a functional VNTR in the promoter region, a dinucleotide repeat in intron 2 (MaoA-CA), and two RFLPs, Fnu4HI in exon 8 and EcoRV in exon 14. There is strong linkage disequilibrium between any two loci. No allele or haplotype showed excess transmission. The extended TDT test was also not significant (P > 0.05). However, there was a deficit of transmission of the 115 bp allele of the MaoA-CA marker to affected offspring by both HRR (P = 0.04) and TDT (P = 0.03). Association tests were also conducted using the George-Elston regression method (the SAGE program ASSOC) with antisocial alcoholism symptom severity. All MaoA markers except for VNTR show significant association (EcoRV, P < 0.01, MaoA-CA, P < 0.05). While these data do not support a direct involvement of MaoA in alcoholism, they suggest that some variants of MaoA affect the number of anti-social symptoms, consistent with previous reports that males missing MaoA activity are severely impulsive and aggressive.