A holistic approach to variation in dopamine genes
Many behavioral disorders have a multifactorial etiology, with a genetic contribution provided by multiple Quantitative Trait Loci (QTLs). It is probable that such QTLs will be functionally related and interacting (epistatic). To investigate this general hypothesis, we have focused on variation in those genes concerned with the receptors and metabolic pathway of a single neurotransmitter, thereby achieving an "Integrated Pathway Genotype Analysis", IPGA. The target for our first holistic approach of this type is the dopamine system. To improve the efficiency of the integrated pathway approach, we have developed a multiplex PCR, whereby six polymorphic repeat markers associated with the following loci are amplified and analyzed simultaneously: monoamine oxidases A and B (MAOA, MAOB), dopamine beta hydroxylase (DBH), phenylalanine hydroxylase (PAH), tyrosine hydroxylase (TH) & the dopamine receptor 5 (DRD5) - coupled with SNP analysis at the COMT, DRD1, DRD2 & DRD3 loci. In a first in-depth investigation employing this approach, we are genotyping approximately 1000 individuals from a birth cohort now reaching the 27th year of a longitudinal study based in Dunedin, New Zealand (Moffitt, Caspi, Rutter, & Silva, 1999, Findings from the first two decades of the Dunedin Longitudinal Study). The genotype data will be examined in the context of life-course persistent, high scores on measures of depression, antisocial behavior, and personality traits.
McClay, J; Caspi, A; Moffitt, TE; Poulton, R; Craig, I
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