title: 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 single-nucleotide 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 family-based 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.
authors.affiliation: Department of Biological Psychology, Vrije Universiteit, Amsterdam, the Netherlands. mf.gosso@vumc.nl
authors.forename: M F
authors.initials: MF
authors.lastname: Gosso
authors.forename: M
authors.initials: M
authors.lastname: van Belzen
authors.forename: E J C
authors.initials: EJ
authors.lastname: de Geus
authors.forename: J C
authors.initials: JC
authors.lastname: Polderman
authors.forename: P
authors.initials: P
authors.lastname: Heutink
authors.forename: D I
authors.initials: DI
authors.lastname: Boomsma
authors.forename: D
authors.initials: D
authors.lastname: Posthuma
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D005828:Genetics, Population; D006801:Humans; D007360:Intelligence / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D043585:Receptor, Muscarinic M2 / Q000235:genetics*; D014429:Twins, Dizygotic; D014430:Twins, Monozygotic
chemical_list: C487078:CHRM2 protein, human; D043585:Receptor, Muscarinic M2