The nicotinic acetylcholine receptor gene CHRNA4 is associated with negative emotionality

Knock-out studies in mice suggest a role of the CHRNA4 gene in anxiety. In the present study we extend this finding to humans by means of a genetic association study. In a sample of N = 574 healthy White participants, the CHRNA4 rs1044396 polymorphism is related to the common variance of several conceptualizations of negative emotionality. Compared to carriers of at least one T-allele, carriers of the homozygous C/C genotype described themselves as more anxious and emotionally unstable on various psychometric personality questionnaires. The scope of the genetic effect is remarkable because other prominent genetic markers for anxiety show specificity for the diagnostic tool used. The present study is the first study that demonstrates the relevance of the CHRNA4 gene for negative emotionality in humans and sets a starting point for further investigations that could inform on the treatment of various affective psychiatric disorders.