Meta-Analysis of Genetic Variation in DTNBP1 and General Cognitive Ability

Abstract

Background The human dystrobrevin-binding protein 1 (DTNBP1) gene has been linked to risk for schizophrenia. Recent studies indicate that several single nucleotide polymorphisms (SNPs) in the DTNBP1 gene may also influence general cognitive ability in both schizophrenic patients and healthy controls. We examined the relationship between DTNBP1 SNPs and general cognitive ability in non-psychiatric healthy samples via meta-analysis. Methods Medline search (12/31/2009) yielded 11 articles examining DTNBP1 variation and general cognitive ability, of which 8 studies had data available encompassing 10 independent cohorts (total n=7,592). The phenotype was defined as either the first principal component score from multiple neuropsychological tests (Spearman's g) or full scale IQ. Meta-analyses were conducted for 9 SNPs for which cognitive data were available from at least 3 cohorts. For each SNP in each cohort, effect size (ES) was computed between major allele homozygotes and minor allele carriers; ES was then pooled across studies using a random effect model. Results Pooled ES's from 2 of the 9 SNPs (rs1018381 and rs2619522) were -0.123 and -0.083, p's<0.01, respectively, suggesting that the minor allele carriers of these SNPs had lower cognitive ability scores than the major allele homozygotes. Results remained significant after examining heterogeneity among samples and potential publication biases. Other SNPs did not show significant effects on general cognitive ability. Conclusion Genetic variation in DTNBP1 modestly influences general cognitive ability. Further studies are needed to elucidate the biological mechanisms that may account for this relationship.

Association of genetic variations in DTNBP1 with cognitive function in schizophrenia patients and healthy subjects

“…The current results are largely consistent with previous studies (Table I) and a recent meta-analysis [Zhang et al, 2010], which reported association with DTNBP1 SNPs with general cognitive ability or various specific cognitive areas. Association between minor allele of rs760761 and lower attention capacity was also found in a previous study of Stefanis et al [2007] Considering that selectively focusing attention requires a widespread network of cortical neurons, major connections of which are glutamatergic [Stan et al, 2009] and that DTNBP1 is functionally related to glutamate release [Numakawa et al, 2004], it is hypothesized that DTNBP1 might affect attention and vigilance functioning through the alteration of glutamatergic system.…”

“…A number of studies tested genotype effect of DTNBP1 on cognitive abilities in healthy subjects, and reported both positive [Burdick et al, 2006;Fallgatter et al, 2006;Stefanis et al, 2007;Zinkstok et al, 2007;Hashimoto et al, 2009Hashimoto et al, , 2010Luciano et al, 2009;Alfimova et al, 2010;Markov et al, 2010;Wolf et al, 2011] and negative [Peters et al, 2008;Kircher et al, 2009] results (Table I). However, a recent meta-analytic study concluded that rs1018381 and rs2719522 of this gene have a modest, but significant, effect on general cognitive ability in healthy subjects [Zhang et al, 2010].…”

Research on Research: A Meta-Scientific Study of Problems and Solutions in Psychological Science

“…Finally, behavior genetic studies link intelligence to genetic variations or estimate heritability using twin designs. Examples include studies about the heritability of cognitive abilities (Beaujean, 2005) or studies linking specific genetic variants to general cognitive ability (Zhang, Burdick, Lencz, & Malhotra, 2010).…”

Pharmacogenetic Approaches to Cognitive Enhancement in Schizophrenia

“…61 Several subsequent candidate gene studies of DTNBP1 have reported similar results, 45−50 with a recent meta-analysis supporting these findings. 62 Several other candidate genes influence glutamatergic neurotransmission and may represent future targets for pharmacogenetic studies of neurocognitive function. For example, G72/G30 (now known as DAOA) is critical in the activation of D-amino acid oxidase and regulates Dserine levels endogenously.…”