A novel differential susceptibility gene: CHRNA4 and moderation of the effect of maltreatment on child personality

J Child Psychol Psychiatry. 2013 Aug;54(8):872-80. doi: 10.1111/jcpp.12031. Epub 2012 Dec 13.


Background: The differential susceptibility hypothesis states that some genetic variants that confer risk in adverse environments are beneficial in normal or nurturing environments. The cholinergic system is promising as a source of susceptibility genes because of its involvement in learning and neural plasticity. The cholinergic receptor gene CHRNA4 has been linked to characteristics related to the personality traits Neuroticism and Openness/Intellect.

Methods: The effects of interaction between CHRNA4 genotype and maltreatment status on child personality were examined in a well matched sample of 339 maltreated and 275 non-maltreated children (aged 8-13 years).

Results: Variation in CHRNA4 interacted with childhood maltreatment to predict personality in a manner indicating differential susceptibility. The interaction of CHRNA4 and maltreatment status predicted Neuroticism and Openness/Intellect. Maltreated children with the rs1044396 T/T genotype scored highest on Neuroticism and showed no effect of genotype on Openness/Intellect. Non-maltreated children with this genotype scored lowest on Neuroticism and highest on Openness/Intellect.

Conclusion: Variation in CHRNA4 appears to contribute to personality by affecting degree of developmental sensitivity to both normal and adverse environments.

Keywords: CHRNA4; Personality; differential susceptibility; genetics; neuroticism; openness/intellect.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Anxiety Disorders / genetics
  • Anxiety Disorders / physiopathology
  • Child
  • Child Abuse / psychology*
  • Child Development / physiology*
  • Female
  • Gene-Environment Interaction*
  • Genetic Predisposition to Disease / genetics*
  • Genetic Predisposition to Disease / psychology
  • Humans
  • Intelligence / genetics
  • Male
  • Neuropsychological Tests
  • Neuroticism
  • Personality / genetics*
  • Predictive Value of Tests
  • Receptors, Nicotinic / genetics*


  • Receptors, Nicotinic
  • nicotinic acetylcholine receptor alpha4 subunit