Sleep bruxism is a sleep-related movement disorder that can be responsible for various pains and dysfunctions in the orofacial region. The aim of the current case–control association study was to investigate the association of genetic, psychological and behavioral factors with sleep bruxism in a Japanese population. Non-related participants were recruited and divided into either a sleep bruxism group (n = 66) or control group (n = 48) by clinical diagnoses and 3-night masseter electromyographic recordings by means of a portable miniature device. The Epworth Sleepiness Scale, Temperament and Character Inventory, NEO-Five Factor Inventory and custom-made questionnaires that asked about familial aggregation, alcohol intake, caffeine intake, cigarette smoking, past stressful life events, daytime tooth-contacting habit, temporomandibular disorder, daily headache, snoring, apnea/hypopnea symptoms, leg-restlessness symptoms and nocturnal-myoclonus symptoms were administered. In addition, 13 polymorphisms in four genes related to serotonergic neurotransmission (SLC6A4, HTR1A, HTR2A and HTR2C) were genotyped. These factors were compared between case (sleep bruxism) and control groups in order to select potential predictors of sleep-bruxism status. The statistical procedure selected five predictors: Epworth Sleepiness Scale, leg-restlessness symptoms, rs6313 genotypes, rs2770304 genotypes and rs4941573 genotypes. A multivariate stepwise logistic regression analysis between the selected predictors and sleep-bruxism status was then conducted. This analysis revealed that only the C allele carrier of HTR2A single nucleotide polymorphism rs6313 (102C>T) was associated significantly with an increased risk of sleep bruxism (odds ratio = 4.250, 95% confidence interval: 1.599–11.297, P = 0.004).This finding suggests a possible genetic contribution to the etiology of sleep bruxism.