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Behavior Genetics

, Volume 37, Issue 2, pp 265–272 | Cite as

Association of CHRM2 with IQ: Converging Evidence for a Gene Influencing Intelligence

  • Danielle M. Dick
  • Fazil Aliev
  • John Kramer
  • Jen C. Wang
  • Anthony Hinrichs
  • Sarah Bertelsen
  • Sam Kuperman
  • Marc Schuckit
  • John Nurnberger Jr
  • Howard J. Edenberg
  • Bernice Porjesz
  • Henri Begleiter
  • Victor Hesselbrock
  • Alison Goate
  • Laura Bierut
Original Paper

Abstract

The cholinergic neurotransmitter system is thought to be involved in many aspects of memory, attention, and higher cognition. In the Collaborative Study on the Genetics of Alcoholism (COGA) sample, we have previously reported linkage and association to the cholinergic muscarinic 2 receptor gene (CHRM2) on chromosome 7 with evoked EEG oscillations (Jones et al. 2004), providing evidence that this gene may be involved in human brain dynamics and cognition. In addition, a small number of genetic markers were genotyped in CHRM2 in the Minnesota Twin and Family Study (Comings et al. 2003) and a Dutch family study (Gosso et al. 2006, in press) and both research groups found evidence that this gene may be involved in intelligence. In the COGA sample, we have extensively genotyped SNPs within and flanking the CHRM2 gene. We find evidence of association with multiple SNPs across CHRM2 and Performance IQ, as measured by the Wechsler Adult Intelligence Scale-Revised (WAIS-R). These results remain significant after taking into account alcohol dependence and depression diagnoses in the sample.

Keywords

Intelligence IQ CHRM2 Cognitive ability Genetics Association analyses 

Notes

Acknowledgments

The Collaborative Study on the Genetics of Alcoholism (COGA), Co-Principal Investigators B. Porjesz, V. Hesselbrock, H. Edenberg, L. Bierut, includes nine different centers where data collection, analysis, and storage take place. The nine sites and Principal Investigators and Co-Investigators are: University of Connecticut (V. Hesselbrock); Indiana University (H.J. Edenberg, J. Nurnberger Jr., P.M. Conneally, T. Foroud); University of Iowa (S. Kuperman, R. Crowe); SUNY Downstate (B. Porjesz); Washington University in St. Louis (L. Bierut, A. Goate, J. Rice); University of California at San Diego (M. Schuckit); Howard University (R. Taylor); Rutgers University (J. Tischfield); Southwest Foundation (L. Almasy). Zhaoxia Ren serves as the NIAAA Staff Collaborator. This national collaborative study is supported by the NIH Grant U10AA008401 from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the National Institute on Drug Abuse (NIDA).

In memory of Henri Begleiter and Theodore Reich, Principal and Co-Principal Investigators of COGA since its inception; we are indebted to their leadership in the establishment and nurturing of COGA, and acknowledge with great admiration their seminal scientific contributions to the field.

References

  1. Barrett JC, Fry B, Maller J, Daly MJ (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21:263–265PubMedCrossRefGoogle Scholar
  2. Boehnke M (1991) Allele frequency estimation from pedigree data. Am J Hum Genet 48:22–25PubMedGoogle Scholar
  3. Bouchard TJ Jr, McGue M (1981) Familial studies of intelligence: A review. Science 212:1055–1059PubMedCrossRefGoogle Scholar
  4. Bucholz KK, Cadoret R, Cloninger CR, Dinwiddie SH, Hesselbrock VM, Nurnberger JJI, Reich T, Schmidt I, Schuckit MA (1994) A new, semi-structured psychiatric interview for use in genetic linkage studies: A report on the reliability of the SSAGA. J Stud Alcohol 55:149–158PubMedGoogle Scholar
  5. Buyske S, Bates ME, Gharani N, Matise TC, Tischfield JA, Manowitz P (2006) Cognitive traits link to human chromosomal regions. Behav Genet 36:65–76PubMedCrossRefGoogle Scholar
  6. Chorney MJ, Chorney K, Seese N, Owen MJ, Daniels J, McGuffin P, Thompson LA, Detterman DK, Benbow C, Lubinski D, Eley T, Plomin R (1998) A quantitative trait locus associated with cognitive ability in children. Psychol Sci 9:159–166CrossRefGoogle Scholar
  7. Comings DE, Wu S, Rostamkhani M, McGue M, Iacono WG, Cheng LS, MacMurray JP (2003) Role of the cholinergic muscarinic 2 receptor (CHRM2) gene in cognition. Mol Psychiatry 8:10–13PubMedCrossRefGoogle Scholar
  8. Devlin B, Daniels M, Roeder K (1997) The heritability of IQ. Nature 388:468–471PubMedCrossRefGoogle Scholar
  9. Dick DM, Aliev F, Bierut L, Goate A, Rice J, Hinrichs AL, Bertelsen S, Wang JC, Dunn G, Kuperman S, Schuckit M, Nurnberger Jr JI, Porjesz B, Begleiter H, Kramer JR, Hesselbrock V (2006) Linkage Analyses of IQ in the Collaborative Study on the Genetics of Alcoholism (COGA) Sample. Behav Genet 36:77–86PubMedCrossRefGoogle Scholar
  10. Dudbridge F (2003) Pedigree disequilibrium tests for multilocus haplotypes. Genet Epidemiol 25:115–121PubMedCrossRefGoogle Scholar
  11. Fenech AG, Billington CK, Swan C, Richards S, Hunter T, Ebejer MJ, Felice AE, Ellul-Micallef R, Hall IP (2004) Novel polymorphisms influencing transcription of the human CHRM2 gene in airway smooth muscle. Am J Respir Cell Mol Biol 30:678–686PubMedCrossRefGoogle Scholar
  12. Flint J (1999) The genetic basis of cognition. Brain 122:2015–2031PubMedCrossRefGoogle Scholar
  13. Gosso MF, van Belzen M, de Geus EJ, Polderman JC, Heutink P, Boomsma DI, Posthuma D (2006) Association between the CHRM2 gene and intelligence in a sample of 304 Dutch families. Genes Brain Behav 5(8):577–584PubMedCrossRefGoogle Scholar
  14. Hesselbrock M, Easton C, Bucholz KK, Schuckit M, Hesselbrock V (1999) A validity study of the SSAGA–A comparison with the SCAN. Addiction 94:1361–1370PubMedCrossRefGoogle Scholar
  15. Hill L, Chorney MJ, Lubinski D, Thompson LA, Plomin R (2002) A quantitative trait locus not associated with cognitive ability in children: A failure to replicate. Psychol Sci 13:561PubMedCrossRefGoogle Scholar
  16. Iverson GL, Woodward TS, Green P (2001) Base rates of WAIS-R VIQ-PIQ differences in 1593 psychiatric inpatients. J Clin Psychol 57:1579–1587PubMedCrossRefGoogle Scholar
  17. Jones KA, Porjesz B, Almasy L, Bierut L, Goate A, Wang JC, Dick DM, Hinrichs AL, Kwon J, Rice J, Rohrbaugh J, Stock H, Wu W, Bauer LO, Chorlian DB, Crowe RR, Edenberg HJ, Foroud T, Hesselbrock V, Kuperman S, Nurnberger Jr JI, O’Connor SJ, Schuckit M, Stimus A, Tischfield JA, Reich T, Begleiter H (2004) Linkage and linkage disequilibrium of evoked EEG oscillations with CHRM2 receptor gene polymorphisms: Implications for human brain dynamics and cognition. Int J Psychophysiol 53:75–90PubMedCrossRefGoogle Scholar
  18. Luciano M, Wright MJ, Duffy DL, Wainwright MS, Zhu G, Evans DM, Geffen GM, Montgomery GW, Martin NG (2006) Genome-wide scan of IQ finds significant linkage to a quantitative trait locus on 2q. Behav Genet 36:45–55PubMedCrossRefGoogle Scholar
  19. Matarazzo JD, Herman DO (1984) Base rate data for the WAIS-R: Test-retest stability and VIQ-PIQ differences. J Clin Neuropsychol 6:351–366PubMedGoogle Scholar
  20. McGue M, Bouchard TJ Jr, Iacono WG, Lykken DT (1993) Behavioral genetics of cognitive ability: A life-span perspective. In: Plomin R, McClearn GE (Eds) Nature, nurture, and psychology. American Psychological Association, Washington, DC, pp. 59–76CrossRefGoogle Scholar
  21. Monks SA, Kaplan NL (2000) Removing the sampling restrictions from family-baed tests of association for a quantitative trait locus. Am J Hum Genet 66:576–592PubMedCrossRefGoogle Scholar
  22. Payton A, Holland F, Diggle PJ, Rabbitt P, Horan M, Davidson Y, Gibbons L, Worthington J, Ollier W, Pendleton N (2003) Cathepsin D exon 2 polymorphism associated with general intelligence in a healthy older population. Mol Psychiatry 8:14–18PubMedCrossRefGoogle Scholar
  23. Plomin R, Hill L, Craig IW, McGuffin P, Purcell S, Sham PC, Lubinski D, Thompson LA, Fisher PJ, Turic D, Owen MJ (2001) A genome-wide scan of 1842 DNA markers for allelic associations with general cognitive ability: a five-stage design using DNA pooling and extreme selected groups. Behav Genet 31:497–509PubMedCrossRefGoogle Scholar
  24. Posthuma D, Luciano M, de Geus EJ, Wright MJ, Slagboom PE, Montgomery GW, Boomsma DI, Martin NG (2005) A genomewide scan for intelligence identified quantitative trait loci on 2q and 6p. Am J Hum Genet 77:318–326PubMedCrossRefGoogle Scholar
  25. Reich T (1996) A genomic survey of alcohol dependence and related phenotypes: Results from the Collaborative Study on the Genetics of Alcoholism (COGA). Alcohol Clin Exp Res 20:133A–137APubMedCrossRefGoogle Scholar
  26. Rosoff ML, Wei J, Nathanson NM (1996) Isolation and characterization of the chicken m2 acetylcholine receptor promoter region: induction of gene transcription by leukemia inhibitory factor and ciliary neurotrophic factor. Proc Natl Acad Sci 93:14889–14894PubMedCrossRefGoogle Scholar
  27. Volpicelli LA, Levey AI (2004) Muscarinic acetylcholine receptor subtypes in cerebral cortex and hippocampus. Prog Brain Res 145:59–66PubMedCrossRefGoogle Scholar
  28. Wang JC, Hinrichs AL, Stock H, Budde J, Allen R, Bertelsen S, Kwon JM, Wu W, Dick DM, Jones K, Nurnberger Jr JI, Tischfield JA, Porjesz B, Edenberg HJ, Hesselbrock V, Crowe R, Schuckit M, Begleiter H, Reich T, Goate A, Bierut L (2004) Evidence of common and specific genetic effects: Association of the muscarinic acetylcholine receptor M2 (CHRM2) gene with alcohol dependence and major depressive syndrome. Hum Mol Genet 13:1903–1911PubMedCrossRefGoogle Scholar
  29. Wechsler D (1981) Wechsler Adult Intelligence Scale-Revised. The Psychological Corporation, New YorkGoogle Scholar
  30. Wechsler D (1997) WAIS-III Wechsler Adult Intelligence Scale. Psychological Corporation, San AntonioGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2006

Authors and Affiliations

  • Danielle M. Dick
    • 1
  • Fazil Aliev
    • 1
    • 2
  • John Kramer
    • 3
  • Jen C. Wang
    • 1
  • Anthony Hinrichs
    • 1
  • Sarah Bertelsen
    • 1
  • Sam Kuperman
    • 3
  • Marc Schuckit
    • 4
  • John Nurnberger Jr
    • 5
  • Howard J. Edenberg
    • 5
  • Bernice Porjesz
    • 6
  • Henri Begleiter
    • 6
  • Victor Hesselbrock
    • 7
  • Alison Goate
    • 1
  • Laura Bierut
    • 1
  1. 1.Department of Psychiatry Washington University in St. LouisSt. LouisUSA
  2. 2.Ankara UniversityAnkaraTurkey
  3. 3.University of IowaIowa CityUSA
  4. 4.University of California at San DiegoSan DiegoUSA
  5. 5.Indiana UniversityIndianapolisUSA
  6. 6.SUNY Health Science Center at BrooklynBrooklynUSA
  7. 7.University of Connecticut School of MedicineFarmingtonUSA

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