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

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

The hydration of the neurotransmitter acetylcholine in aqueous solution

Neutron diffraction augmented with hydrogen isotope substitution has been used to examine the water structure around the acetylcholine molecular ion in aqueous solution. It is shown that the nearest-neighbor water molecules in the region around the trimethylammonium headgroup are located either in a ring around the central nitrogen atom or between the carbon atoms, forming a sheath around the onium group. Moreover the water molecules in this cavity do not bond to the onium group but rather form hydrogen bonds with water molecules in the surrounding aqueous environment. Given that in the bound state the onium headgroup must be completely desolvated, the absence of bonding between the onium headgroup and the surrounding water solvent may be selectively favorable to acetylcholine-binding in the receptor site. Away from the headgroup, pronounced hydrogen-bonding of water to the carbonyl oxygen is observed, but not to the ether oxygen in the acetylcholine chain