Journal de recherche et de thérapie en toxicomanie

Abstrait

Association between Genetic Polymorphism rs2952768, Close to the METTL21A and CREB1 Genes, and Intellectual Ability in Healthy Subjects

Daisuke Nishizawa, Kazutaka Ohi, Ryota Hashimoto, Hidenaga Yamamori, Yuka Yasuda, Michiko Fujimoto, Satomi Yano-Umeda, Masatoshi Takeda and Kazutaka Ikeda

Objective: Human intelligence, which represents a set of cognitive abilities, is assumed to be a highly heterogenic trait. The Intelligence Quotient (IQ) is the most widely used index for characterizing human intelligence in psychometric studies, and knowledge of the genes associated with IQ has continuously grown. Several previous reports indicated that IQ may be associated with addictive behaviors or the use of addictive substances, although the trend toward an association is not straightforward and depends on the substances abused. To explore the genetic factors that contribute to IQ, we conducted an association study of a genetic polymorphism, rs2952768. The rs2952768 single-nucleotide polymorphism (SNP) was recently reported to be associated with human opioid sensitivity and shown to be associated with the efficacy of opioid analgesics, severity of substance dependence, and mRNA expression levels of a neighboring gene, CREB1.

Methods: The present study used data from 298 biologically unrelated Japanese subjects. Psychiatrically, medically, and neurologically healthy subjects were evaluated using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Non-Patient Edition (SCID-I/NP), to exclude individuals who had substance-related disorders, who had received psychiatric medications, or who had first- or second-degree relatives with psychiatric disorders. Genotyping was performed using the Affymetrix Genome-Wide Human SNP Array 6.0. The rs2952768 SNP close to the METTL21A gene was extracted from this dataset. Multiple linear regression analysis was performed to compare intellectual ability among rs2952768 SNP genotypes.

Results: A significant effect of the SNP genotype was observed on current IQ (β = -2.27, p = 0.026). The number of non-risk major C allele for drug and alcohol dependence was correlated with higher IQ scores.

Conclusion: The present results suggest that the rs2952768 SNP, which was identified as a potent SNP associated with human opioid sensitivity, is also one of the genetic factors that contribute to human intellectual ability.