Rare variants may be important reservoirs of risk for complex genetic traits, including neuropsychiatric traits (22,23). However, the role of rare variants is largely unexplored for ND. Because of the inconsistency of the evidence common polymorphisms in CHRNA4 as contributors to ND risk and the functional importance of the α4 subunit of the nAChR for nicotine actions, we hypothesized that rare variants in CHRNA4 modulate risk for ND.
