CHRNA5 and nicotine dependence: Pleiotropy has also been reported at the level of single genes: For example, a missense polymorphic variant (rs16969968:G>A, p.Asp398Asn) at CHRNA5, encoding the α5 nicotinic acetylcholine receptor, leads to hypofunction of the protein and is likely the most robust and replicated association with risk for nicotine addiction [81].