Complex diseases are influenced by both genetic and environmental factors.Besides concerning genetic variations and their association with human diseases,the epigenetic gene-environment interaction (G × E) may be also a potential mechanism underlying diseases,and regulatory variation may be involved in such mechanism as a bridge factor.In recent years we have done efforts on regulatory variation annotation to assist researchers on exploring regulatory variations for in-depth molecular mechanisms of complex phenotypes[1,2];we also carried on the exploration on epigenetic regulation process that induced by the environmental factor chronic stress (CS)[3,4].Through these efforts,we propose to partly explain biological mechanism of G×E in CS induced complex diseases,and to identify key regulatory variations and relevant epigenetic mechanisms in such processes.