Abstract # 168:

Scheduled for Sunday, August 27, 2017 10:00 AM-10:15 AM: (Grand Ballroom) Oral Presentation


WHOLE EXOME SEQUENCING IDENTIFIES A GABRA6 VARIANT THAT PREDICTS ALCOHOL RESPONSE AND CONSUMPTION IN RHESUS MACAQUES

C. S. Barr1, C. A. Driscoll1, S. G. Lindell1, S. J. Suomi1 and J. D. Higley2
1NIH, Rockville, MD 20842, USA, 2Brigham Young University
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     Genetic factors predicting behavioral style may also influence alcohol use in modern humans. Exploiting the phylogenetically close relationship between human and macaque we have used a human-based exon assay to sequence exomes of rhesus macaques, selected based on variation in temperament. Among the damaging non-synonymous SNPs identified was one in the GABRA6 gene, a known candidate for alcohol response differences in humans and rodents. Using datasets archived at the NIHAC, we examined whether rhGABRA6 genotype predicted alcohol response and consumption. Nursery- and mother-reared macaques were administered ethanol (2g/kg, IV), placed in a padded testing room and scored for their intoxication ratings. Animals were later given access to an 8.4% aspartame-sweetened alcohol solution. Genotyping was performed by TaqMan, and data were analyzed by ANOVA with rearing and genotype as independent variables. Carriers of the variant allele had higher intoxication scores. There was also a rearing by GABRA6 genotype interaction on alcohol self-administration. Nursery-reared macaques carrying the variant allele did not exhibit upregulated alcohol self-administration relative to homozygotes for the ancestral allele. Although little has been done to examine GABRA6 variation as it relates to alcohol abuse or dependence in human subjects, our data support a role for this SNP in protecting against early stress-induced increases in alcohol intake, suggesting that damaging variation at this gene could serve a protective role for alcohol missuse in human subjects.