Office of the Chief

Section on Comparative Behavioral Genetics

Section on Human Genetics

The Section on Comparative Behavioral Genetics studies the relationship between genomic variations and behavioral traits that are risk factors for alcohol use disorders. The Section uses genome-wide scanning techniques to identify single nucleotide polymorphisms (SNPs) that might be involved in adaptations to stressful environments in primates. Such analyses have yielded more than half a million SNPs, and subsequent analyses suggest that genes for brain-derived neurotrophic factor (BNDF), neuropeptide Y, the oxytocin receptor (OXYR), and serotonin transporters play important adaptive roles. The Section has characterized 8 SNPs in the regulatory region of SLC6A4, a serotonin transporter, and results suggest that alleles in this gene confer vulnerabilities to psychiatric disorders. The Section has also identified non-synonymous SNPs in the BNDF gene, which is critical for neuronal survival, development and plasticity. Further analyses on interactions between BNDF genotypes and the rearing conditions of rhesus macaques showed that the Val46Met genotype moderated effects on orientation, motor maturity, activity and state control in peer-raised monkeys. Additionally, the Section has identified 4 non-synonymous SNPs in the OXTR gene, which indicate key evolutionary differences in the regulation of the gene in humans and monkeys. Further analyses of the first intron and second exon of the human gene suggest that these sites are evolutionarily dynamic and have the potential for multiple pathways of epigenetic regulation.

The Section on Human Genetics is searching for genetic variations that increase the susceptibility for alcoholism and other substance-related and psychiatric disorders. Much of this work involves the detection of single-nucleotide variations, genotyping, genome linkage studies, epigenetic and transcriptome analyses, and functional studies of receptor variants. For example, the Section has identified an association between GABRA2 and GABRG1 and alcoholism, a linkage between DISC1 and schizoaffective disorder, and an MnSOD2 gene effect on grey matter shrinkage in chronic alcoholics. The Section is studying the effects of DNA methylation, and chromatic and RNA metabolism on fetal alcohol syndrome, as well as the effects of haplotype-based Neuropeptide Y gene expression variation on emotion and stress response. The Section has demonstrated an association between CRH-BP and alcohol use and anxiety in Caucasians and Plains Indians, and it has used ancestry scores to show that heroin and cocaine dependence in African Americans is attributable to socioeconomic factors, as opposed to African ancestry. The Section has contributed to work that shows that the Asn40Asp allele predicts a positive treatment response to naltrexone for alcoholism, and it conducted many gene/environment interaction studies for alcoholism and depression. The Section’s other work includes numerous studies that identified connections between genetic variations (e.g., HTTLPR, COMT, and alleles for aldehyde dehydrogenase and neuropeptide Y), intermediate phenotypes (e.g., fMRI emotional responses, trait anxiety, and cognitive functions) and a range of substance use and psychiatric disorders (e.g., alcoholism, drug addiction and suicidality).