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Genetic Polymorphism of GABRR2 Modulates Individuals’ General Cognitive Ability in Healthy Chinese Han People

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Abstract

Previous studies have indicated that the cognitive impairment or deficit is associated with GABAergic signaling in central nervous system. Inspired by the finding that receptor GABRR2 modulates concentration of GABA and phasic inhibitory GABAergic transmission in brain. This study investigated to what extent a genetic variant (c.1423C>T, rs282129) of GABRR2 gene modulates individuals’ general cognitive ability in 987 Chinese Han people. Results showed a significant influence of GABRR2 gene polymorphism on individuals’ Raven’s Standard Progressive Matrices (RSPM) performance (F = 3.58, P = .028 by ANOVA and χ 2 = 9.35, P = .009 by K–W test, respectively), even if non-genetic factors were partialed out (gender, major, types of birthplace, and socioeconomic index) (B = −.67, SE = .26, t = 2.63, P = .009). The finding provided a strong evidence, to our knowledge, for the view that genetic variant of GABRR2 gene may contribute to the difference of individuals’ general cognitive ability, independently.

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References

  • Alakuijala A, Alakuijala J, Pasternack M (2006) Evidence for a functional role of GABAC receptors in the rat mature hippocampus. Eur J Neurosci 23:514–520

    Article  PubMed  Google Scholar 

  • Auger ML, Floresco SB (2014) Prefrontal cortical GABA modulation of spatial reference and working memory. Int J Neuropsychopharmacol 18. doi:10.1093/ijnp/pyu013

  • Bhandage AK, Hellgren C, Jin Z, Olafsson EB, Sundström-Poromaa I, Birnir B (2015) Expression of GABA receptors subunits in peripheral blood mononuclear cells is gender dependent, altered in pregnancy and modified by mental health. Acta Physiol 213:575–585

    Article  CAS  Google Scholar 

  • Bodizs R, Gombos F, Ujma PP, Kovacs I (2014) Sleep spindling and fluid intelligence across adolescent development: sex matters. Front Hum Neurosci 8:952. doi:10.3389/fnhum.2014.00952

    PubMed  PubMed Central  Google Scholar 

  • Cartegni L, Wang J, Zhu Z, Zhang MQ, Krainer AR (2003) ESEfinder: a web resource to identify exonic splicing enhancers. Nucleic Acids Res 31:3568–3571

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cellot G, Cherubini E (2014) GABAergic signaling as therapeutic target for autism spectrum disorders. Front Pediatr 2:70. doi:10.3389/fped.2014.00070

    Article  PubMed  PubMed Central  Google Scholar 

  • Deary IJ (2012) Intelligence. Annu Rev Psychol 63:453–482. doi:10.1146/annurev-psych-120710-100353

    Article  PubMed  Google Scholar 

  • Enomoto T, Maric TT, Floresco SB (2011) Reducing prefrontal gamma-aminobutyric acid activity induces cognitive, behavioral, and dopaminergic abnormalities that resemble schizophrenia. Biol Psychiatry 69:432–441

    Article  CAS  PubMed  Google Scholar 

  • Fairbrother WG, Yeh R-F, Sharp PA, Burge CB (2002) Predictive identification of exonic splicing enhancers in human genes. Science 297:1007–1013

    Article  CAS  PubMed  Google Scholar 

  • Gauderman WJ, Morrison JM (2006) Quanto: a computer program for power and sample size calculations for genetic-epidemiology studies. http://giostats.usc.edu/software. Accessed 1 Oct 2014

  • Gonzalez-Gomez PL et al (2014) Cognitive ecology in hummingbirds: the role of sexual dimorphism and its anatomical correlates on memory. PLoS One 9:e90165. doi:10.1371/journal.pone.0090165

    Article  PubMed  PubMed Central  Google Scholar 

  • Goren A et al (2006) Comparative analysis identifies exonic splicing regulatory sequences—the complex definition of enhancers and silencers. Mol Cell 22:769–781

    Article  CAS  PubMed  Google Scholar 

  • Harvey VL, Duguid IC, Krasel C, Stephens GJ (2006) Evidence that GABA ρ subunits contribute to functional ionotropic GABA receptors in mouse cerebellar Purkinje cells. J Physiol 577:127–139

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kofuji P, Wang JB, Moss SJ, Huganir RL, Burt DR (1991) Generation of two forms of the gamma-aminobutyric acid A receptor gamma 2-subunit in mice by alternative splicing. J Neurochem 56:713–715

    Article  CAS  PubMed  Google Scholar 

  • Kumari R, Lakhan R, Kalita J, Garg RK, Misra UK, Mittal B (2011) Potential role of GABAA receptor subunit; GABRA6, GABRB2 and GABRR2 gene polymorphisms in epilepsy susceptibility and pharmacotherapy in North Indian population. Clin Chim Acta 412:1244–1248. doi:10.1016/j.cca.2011.03.018

    Article  CAS  PubMed  Google Scholar 

  • Liu B et al (2004) Single cell RT-PCR demonstrates differential expression of GABAC receptor rho subunits in rat hippocampal pyramidal and granule cells. Brain Res Mol Brain Res 123:1–6. doi:10.1016/j.molbrainres.2003.12.011

    Article  CAS  PubMed  Google Scholar 

  • Liu J, Gong P, Zhou X (2014) The association between romantic relationship status and 5-HT1A gene in young adults. Sci Rep 4:7049. doi:10.1038/srep07049

    Article  PubMed  PubMed Central  Google Scholar 

  • Mackintosh N, Mackintosh NJ (2011) IQ and human intelligence. Oxford University Press, New York

    Google Scholar 

  • Marenco S et al (2010) Genetic modulation of GABA levels in the anterior cingulate cortex by GAD1 and COMT. Neuropsychopharmacology 35:1708–1717. doi:10.1038/npp.2010.35

    CAS  PubMed  PubMed Central  Google Scholar 

  • Modrego PJ, Fayed N, Pina MA (2014) Conversion from mild cognitive impairment to probable Alzheimer’s disease predicted by brain magnetic resonance spectroscopy. Am J Psychiatry 10:e108883

    Google Scholar 

  • Olsen RW, Sieghart W (2008) International Union of Pharmacology. LXX. Subtypes of γ-aminobutyric acid A receptors: classification on the basis of subunit composition, pharmacology, and function. Pharmacol Rev 60:243–260

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ota VK et al (2013) Neurotransmitter receptor and regulatory gene expression in peripheral blood of Brazilian drug-naive first-episode psychosis patients before and after antipsychotic treatment. Psychiatry Res 210:1290–1292. doi:10.1016/j.psychres.2013.09.016

    Article  CAS  PubMed  Google Scholar 

  • Ota VK et al (2014) Evaluation of neurotransmitter receptor gene expression identifies GABA receptor changes: a follow-up study in antipsychotic-naive patients with first-episode psychosis. J Psychiatr Res 56:130–136. doi:10.1016/j.jpsychires.2014.05.012

    Article  PubMed  Google Scholar 

  • Paine TA, LE Slipp, Carlezon WA, Jr (2011) Schizophrenia-like attentional deficits following blockade of prefrontal cortex GABAA receptors. Neuropsychopharmacology 36:1703–1713. doi:10.1038/npp.2011.51

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Plomin R (1999) Genetics and general cognitive ability. Nature 402:C25–C29. doi:10.1038/35011520

    Article  CAS  PubMed  Google Scholar 

  • Plomin R, Deary I (2014) Genetics and intelligence differences: five special findings. Mol Psychiatry. doi:10.1038/mp.2014.105

    PubMed Central  Google Scholar 

  • Plomin R, Owen MJ, McGuffin P (1994) The genetic basis of complex human behaviors. Science 264:1733–1739

    Article  CAS  PubMed  Google Scholar 

  • Reumers J, Schymkowitz J, Ferkinghoff-Borg J, Stricher F, Serrano L, Rousseau F (2005) SNPeffect: a database mapping molecular phenotypic effects of human non-synonymous coding SNPs. Nucleic Acids Res 33:D527–D532

    Article  CAS  PubMed  Google Scholar 

  • Rozzo A, Armellin M, Franzot J, Chiaruttini C, Nistri A, Tongiorgi E (2002) Expression and dendritic mRNA localization of GABAC receptor rho1 and rho2 subunits in developing rat brain and spinal cord. Eur J Neurosci 15:1747–1758

    Article  PubMed  Google Scholar 

  • Sahun I et al (2014) Cognition and hippocampal plasticity in the mouse is altered by monosomy of a genomic region implicated in Down syndrome. Genetics 197:899–912. doi:10.1534/genetics.114.165241

    Article  PubMed  PubMed Central  Google Scholar 

  • Sanacora G, Saricicek A (2007) GABAergic contributions to the pathophysiology of depression and the mechanism of antidepressant action. CNS Neurol Disord Drug Targets 6:127–140

    Article  CAS  PubMed  Google Scholar 

  • Security CLaS (2007) Occupational classification system of the People’s Republic of China. China Labor and Social Security Publisher, Beijing

    Google Scholar 

  • Song Z, Zhu H, Wei X (2002) The parents’ occupation types influence on children’s psychological development. Acad Explor 4:3

    Google Scholar 

  • Vanderpool M, Catano VM (2008) Comparing the performance of Native North Americans and predominantly White military recruits on verbal and nonverbal measures of cognitive ability. Int J Sel Assess 16:239–248

    Article  Google Scholar 

  • Wagner K, Edson K, Heginbotham L, Post M, Huganir RL, Czernik AJ (1991) Determination of the tyrosine phosphorylation sites of the nicotinic acetylcholine receptor. J Biol Chem 266:23784–23789

    CAS  PubMed  Google Scholar 

  • Wang Y, Shi T (2012) Integration of multiple perspectives in choice of college majors. J China Women’s Univ 2012:55–61

  • Wang KS, Liu XF, Aragam N (2010) A genome-wide meta-analysis identifies novel loci associated with schizophrenia and bipolar disorder. Schizophr Res 124:192–199. doi:10.1016/j.schres.2010.09.002

    Article  PubMed  Google Scholar 

  • Wicherts JM, Vorst HCM (2010) The relation between specialty choice of psychology students and their interests, personality, and cognitive abilities. Learn Individ Differ 20:7. doi:10.1016/j.lindif.2010.01.004

    Google Scholar 

  • Xuei X et al (2010) GABRR1 and GABRR2, encoding the GABA-A receptor subunits rho1 and rho2, are associated with alcohol dependence American journal of medical genetics Part B. Neuropsychiatr Genet 153B:418–427. doi:10.1002/ajmg.b.30995

    CAS  Google Scholar 

  • Zhang HC, Wang XP (1985) The Raven’s progressive matrices (RSPM) manual (revised edited for urban population). Beijing Normal University Press, Beijing

    Google Scholar 

  • Zhang D, Pan ZH, Awobuluyi M, Lipton SA (2001) Structure and function of GABA(C) receptors: a comparison of native versus recombinant receptors. Trends Pharmacol Sci 22:121–132

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We are grateful to all the participating families and to our clinical collaborators for subject recruitment and evaluation. This work was supported by grants from the National Natural Science Foundation of China (Nos. 31340028, 31100899, 31371327 and J1210063).

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    Authors and Affiliations

    1. Key Laboratory of Resource Biology and Biotechnology in Western China (Ministry of Education), Institute of Population and Health, College of Life Science, Northwest University, Xi’an, 710069, China

      Zhe Ma, Binbin Niu, Zhangyan Shi, Junlin Li, Fuchang Zhang, Xiaocai Gao & Kejin Zhang

    2. Department of Applied Psychology, Institute of Applied Psychology, College of Public Management, Northwest University, Xi’an, 710069, China

      Jian Wang, Fuchang Zhang & Xiaocai Gao

    3. School of Public Management, Institute of Application Psychology, Institute of Population and Health, Northwest University, Xi’an, 710127, China

      Xiaocai Gao

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    1. Zhe Ma
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    4. Junlin Li
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    Correspondence to Xiaocai Gao or Kejin Zhang.

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    Zhe Ma and Binbin Niu have contributed equally to this article.

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    Ma, Z., Niu, B., Shi, Z. et al. Genetic Polymorphism of GABRR2 Modulates Individuals’ General Cognitive Ability in Healthy Chinese Han People. Cell Mol Neurobiol 37, 93–100 (2017). https://doi.org/10.1007/s10571-016-0347-2

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