Association of CHRM2 with IQ: Converging Evidence for a Gene Influencing Intelligence
- 652 Downloads
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.
KeywordsIntelligence IQ CHRM2 Cognitive ability Genetics Association analyses
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.
- 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
- 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
- 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
- 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
- Wechsler D (1981) Wechsler Adult Intelligence Scale-Revised. The Psychological Corporation, New YorkGoogle Scholar
- Wechsler D (1997) WAIS-III Wechsler Adult Intelligence Scale. Psychological Corporation, San AntonioGoogle Scholar