Study Objectives: Sleeping 7 to 8 hours per night appears to be optimal, since both shorter and longer sleep times are related to increased morbidity and mortality. Depressive disorder is almost invariably accompanied by disturbed sleep, leading to decreased sleep duration, and disturbed sleep may be a precipitating factor in the initiation of depressive illness. Here, we examined whether, in healthy individuals, sleep duration is associated with genes that we earlier found to be associated with depressive disorder. Design: Population-based molecular genetic study. Setting: Regression analysis of 23 risk variants for depressive disorder from 12 genes to sleep duration in healthy individuals. Participants: Three thousand, one hundred, forty-seven individuals (25-75 y) from population-based Health 2000 and FINRISK 2007 samples. Measurements and Results: We found a significant association of rs687577 from GRIA3 on the X-chromosome with sleep duration in women (permutation-based corrected empirical P = 0.00001, beta = 0.27; Bonferroni corrected P = 0.0052; f = 0.11). The frequency of C/C genotype previously found to increase risk for depression in women was highest among those who slept for 8 hours or less in all age groups younger than 70 years. Its frequency decreased with the lengthening of sleep duration, and those who slept for 9 to 10 hours showed a higher frequency of C/A or A/A genotypes, when compared with the midrange sleepers (7-8 hours) (permutation-based corrected empirical P = 0.0003, OR = 1.81). Conclusions: The GRIA3 polymorphism that was previously found to be associated with depressive disorder in women showed an association with sleep duration in healthy women. Mood disorders and short sleep may share a common genetic background and biologic mechanisms that involve glutamatergic neurotransmission.