Association between the CHRM2 gene and intelligence in a sample of 304 Dutch families

Abstract

The CHRM2 gene is thought to be involved in neuronal excitability, synaptic plasticity and feedback regulation of acetylcholine release and has previously been implicated in higher cognitive processing. In a sample of 667 individuals from 304 families, we genotyped three singlenucleotide polymorphisms (SNPs) in the CHRM2 gene on 7q31-35. From all individuals, standardized intelligence measures were available. Using a test of within-family association, which controls for the possible effects of population stratification, a highly significant association was found between the CHRM2 gene and intelligence. The strongest association was between rs324650 and performance IQ (PIQ), where the T allele was associated with an increase of 4.6 PIQ points. In parallel with a large familybased association, we observed an attenuated -although still significant -population-based association, illustrating that population stratification may decrease our chances of detecting allele-trait associations. Such a mechanism has been predicted earlier, and this article is one of the first to empirically show that family-based association methods are not only needed to guard against false positives, but are also invaluable in guarding against false negatives.

Risk gene variants for nicotine dependence in the CHRNA5–CHRNA3–CHRNB4 cluster are associated with cognitive performance

“…The majority of these genes has been related to dopaminergic and cholinergic neurotransmission including COMT (catechol-O-methyltransferase), DRD2 (dopamine receptor D2), the two muscarinic receptor genes CHRM1 and CHRM2 and the nicotinic receptor gene CHRNA4 [e.g., Egan et al, 2001;Comings et al, 2003;Gallinat et al, 2003;Winterer and Goldman, 2003;Espeseth et al, 2006;Gosso et al, 2006;Savitz et al, 2006;Winterer et al, 2006Winterer et al, , 2007Rigbi et al, 2008Rigbi et al, , 2010. The results from the present explorative study possibly point to gene cluster involved in cholinergic, that is, nicotinic neurotransmission, supporting associations between SNPs from the CHRNA5-CHRNA3-CHRNB4 locus and several IQ (sub-)-cales-most notably with the verbal IQ subscale ''Similarities'' and the performance IQ subscale ''Object Assembly.''…”

A genome-wide investigation into parent-of-origin effects in autism spectrum disorder identifies previously associated genes including SHANK3

“…This area has been previously linked with IQ and one of the strongest linkage signals reported for ASD occurred at 7q within 1.6 kb of the CHRM2 gene. 36 One of our top hits for maternal genetic effects was identified on chromosome 22 in the SHANK3 gene (rs5770820, hg18 chr22:g.49497339G4A, allele = A, S 1 = 1.25, Wald P-value = 5.54 × 10 − 5 , see Figure 1). Disruptions Figure 1 shows that there are no SNPs in high LD with rs5770820 (the SNP in highest LD was rs739365, R 2 = 0.65) due to the limited number of SNPs common to all three arrays in the SSC data set.…”

Catechol O-methyl transferase and dopamine D2 receptor gene polymorphisms: evidence of positive heterosis and gene–gene interaction on working memory functioning

“…Results on cognitive effects of two other genes are described elsewhere. 39,40 Statistical analyses Allele frequencies of the COMT Val 108/158 Met and DRD2 A1/A2 polymorphisms were estimated in both cohorts using Haploview (http://www.broad. mit.edu/mpg/haploview), in which a Hardy -Weinberg test is implemented, based on an exact calculation of the probability of observing a certain number of heterozygotes conditional on the number of copies of the minor SNP allele.…”