The association of DNA sequence variation at the MAOA genetic locus with quantitative behavioural traits in normal males.
Monoamine oxidase A (MAOA) catalyses the oxidative deamination of biogenic amines including neurotransmitters, mainly norepinephrine and serotonin in the brain and peripheral tissues. A nonsense mutation in the gene was shown to be involved in a rare X-linked behavioural syndrome, which includes impaired impulse control, aggression and borderline mental retardation (Brunner syndrome). Several recent studies have shown the association of genetic variation of a VNTR in the gene promoter with various pathological behavioural traits. In the present study the association of MAOA genetic variation with a large set of quantitative behavioural traits in normal individuals has been examined. DNA samples from 421 unrelated males were genotyped for 14 SNPs and for the promoter VNTR at the MAOA locus. An additional 16 SNPs were genotyped at apparently neutral loci across the X chromosome to serve as a genomic control for possible false positive associations due to population structure. Behavioural traits were measured using the NEO psychometric questionnaire, which is based on a 5-axis model of personality, and consists of 30 different quantitative traits. There was a robust association of the A2 ("straightforwardness") facet with common allelic variants at the promoter VNTR. Most of the tested traits were not associated with the VNTR despite reasonable power, thus demonstrating that the VNTR influence on quantitative behavioural traits in normal males may be very specific. In contrast, several traits of the C ("conscientiousness") axis were associated with less common SNP-defined haplotypes. Hence, it appears that common genetic variation at the VNTR contributes to the behavioural attribute of "straightforwardness", while rare haplotypes defined by SNPs downstream of the transcription start site may contribute to "conscientiousness". This study is used to address the validation, interpretation and limitation of genetic association studies of quantitative behavioural traits.
Rosenberg
Shai
S
Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa, Israel. rozenber@tx.technion.ac.il
Templeton
Alan R
AR
Feigin
Paul D
PD
Lancet
Doron
D
Beckmann
Jacques S
JS
Selig
Sara
S
Hamer
Dean H
DH
Skorecki
Karl
K
D001741:Black or African American / Q000235:genetics; D000704:Analysis of Variance; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D001519:Behavior; D014644:Genetic Variation; D005824:Genetics, Behavioral; D005828:Genetics, Population; D005838:Genotype; D006239:Haplotypes; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D008297:Male; D018598:Minisatellite Repeats; D008995:Monoamine Oxidase / Q000235:genetics*; D010641:Phenotype; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D040641:Quantitative Trait Loci / Q000235:genetics*; D044465:White People / Q000235:genetics
D008995:Monoamine Oxidase