Sensation seeking is a heritable personality trait that has been reliably linked to behavioral disorders. The dopamine system has been hypothesized to contribute to variations in sensation seeking between different individuals, and both experimental and observational studies in humans and nonhuman animals provide evidence for the involvement of the dopamine system in sensation-seeking behavior. In this study, we took a candidate-system approach to genetic association analysis of sensation-seeking behavior. We analyzed single-nucleotide polymorphisms (SNPs) from a number of dopaminergic genes. Using 273 SNPs from eight dopamine genes in a sample of 635 unrelated individuals, we examined the aggregate effect of SNPs that were significantly associated with sensation-seeking behavior. Multiple SNPs in four dopamine genes accounted for significant variance in sensation-seeking behavior between individuals. These results suggest that multiple SNPs, aggregated within genes that are relevant to a specific neurobiological system, form a genetic-risk score that may explain a significant proportion of observed variance in human traits such as sensation-seeking behavior.
Bibliographical noteFunding Information:
The Study of Addiction: Genetics and Environment (SAGE) is one of the genome-wide association studies funded as part of the Gene Environment Association Studies (GENEVA) under the National Institutes of Health (NIH) Genes, Environment and Health Initiative (GEI). Funding support for SAGE was provided through GEI (U01 HG004422). Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by the GENEVA Coordinating Center (U01 HG004446). Support for collection of data sets and samples was provided by the Collaborative Study on the Genetics of Alcoholism (COGA; U10 AA008401), the Collaborative Genetic Study of Nicotine Dependence (COGEND; P01 CA089392), and the Family Study of Cocaine Dependence (FSCD; R01 DA013423). Funding support for genotyping, which was performed at the Johns Hopkins University Center for Inherited Disease Research, was provided by the NIH GEI (U01HG004438), the National Institute on Alcohol Abuse and Alcoholism (NIAAA), the National Institute on Drug Abuse (NIDA), and the NIH contract “High Throughput Genotyping for Studying the Genetic Contributions to Human Disease” (HHSN268200782096C). This national collaborative study is supported by NIH Grant U10AA008401 from NIAAA and NIDA. S. Saccone was supported by NIH Grant DA024722.
- association study
- candidate gene
- sensation seeking