Distinct life history patterns have been observed and characterized in humans and appear to have a heritable component. The specific genetic variation responsible for the heritability is unknown. This study tested two plausible candidate genes for association with human life history characteristics using a sample of Caucasian men and women taken from a large Australian community survey. Associations were found between two polymorphisms within the AVPR1A gene and age of first sexual intercourse in men and women. An association was also found between a polymorphism in the OXTR gene with the tendency to parent children at an earlier age in females. This study is the first to report associations between AVPR1A and OXTR genetic variation with life history traits in humans.
Previous reports have identified an interaction between an MAOA promoter polymorphism and childhood adversity for antisocial behavioral outcomes in males. This study attempted to replicate this finding in an Australian community survey of 1,002 Caucasian men aged 20-24 years. Greater childhood adversity was associated with later antisocial behavior, but no association was observed between MAOA genotype and antisocial behavior, and no interaction was found between childhood adversity and MAOA genotype for antisocial behavior. This study does not support previous reports of an interaction between MAOA genotype and childhood adversity for antisocial behavior in males.
This study sought to test 15 simple sequence repeat polymorphisms within 10 candidate genes for association with antisocial behavioural traits. Genes included were those known to regulate dopamine synthesis and transmission in the brain (DBH, DRD2, MAOA, TFAP2B, NR4A2, LMX1B) and those involved in the differentiation of social and sexual behaviour in men and women (AR, ESR1, OXTR, AVPR1A). Participants were Caucasians (men=1007, women=1089) aged 20-24 years who were assessed for indicators of antisocial traits such as pseudo-maturity, substance misuse and unstable lifestyle. Significant associations for antisocial traits were found with AR and ESR1 polymorphisms in men, and with polymorphisms within NR4A2 and TFAP2B in women. The association with TFAP2B remained significant after correction for multiple testing. This pattern of associations suggests that genetic variation within transcription factors may in part explain the variation observed in the population for antisocial behavioural phenotypes.
Anxiety problems and associated temperamental traits are multifactorial, determined by the interaction of genetic and environmental factors. Genetic effects may involve both neurotransmitters and hormones. A good candidate gene for association with anxiety-related traits is the estrogen receptor (ESRalpha). Estrogen exerts an effect on mood and behavior in humans through gene regulation on binding to estrogen receptor protein. Association between ESRalpha polymorphism and anxiety-related traits was investigated in a cohort of 680 Australian adolescents studied from 4-8 months to 15-16 years of age. Genotype frequencies were estimated for polymorphic PvuII and XbaI restriction sites in intron 1 and a microsatellite [(TA)(n)] locus 5' of ESRalpha. There was strong linkage disequilibrium between the three loci and a significant sex difference was observed in allele (for (TA)(n), PvuII) and genotype (for XbaI) frequencies. There were no significant allelic or genotypic differences in anxiety-related traits for the three loci tested. However, some significant associations were found for PvuII/(TA)(n) and XbaI/(TA)(n) two-locus genotypes and anxiety, accounting for between 1.6% and 2.8% of the total variance for anxiety in this population. The discordance in Hardy-Weinberg proportions at the XbaI locus between the sexes is an important finding, perhaps indicating a sex-specific role for ESRalpha in fetal survival.
Simple sequence repeats (SSRs) have traditionally been used as markers in gene mapping studies and typing for forensic purposes. Recently there has been some speculation that this type of genetic variation also plays a more direct role in influencing gene expression and hence complex phenotypic outcomes such as human behavior. For this reason it is interesting to investigate SSRs linked to candidate genes for various complex phenotypes. An economical multiplex PCR-based assay was designed to simultaneously genotype individuals at 15 loci across 10 candidate genes for human behavioural phenotypes, including seven loci previously unreported in Caucasians (five unreported in any population). All loci were tested for Hardy-Weinberg equilibrium and for two-locus Linkage Disequilibrium. Ewens-Watterson neutrality testing indicated possible selection at a previously unreported DRD2 locus.
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