AbstractIntroduction The circadian clock plays an important role in several aspects of female reproductive biology. Evidence linking circadian clock-related genes to pregnancy outcomes has been inconsistent. We sought to examine whether variations in single nucleotide polymorphisms (SNPs) of circadian clock genes are associated with \PA\ risk. Methods Maternal blood samples were collected from 470 \PA\ case and 473 controls. Genotyping was performed using the Illumina Cardio-MetaboChip platform. We examined 119 \SNPs\ in 13 candidate genes known to control circadian rhythms (e.g., CRY2, ARNTL, and RORA). Univariate and penalized logistic regression models were fit to estimate odds ratios (ORs); and the combined effect of multiple \SNPs\ on \PA\ risk was estimated using a weighted genetic risk score (wGRS). Results A common \SNP\ in the \RORA\ gene (rs2899663) was associated with a 21% reduced odds of \PA\ (P < 0.05). The odds of \PA\ increased with increasing wGRS (Ptrend < 0.001). The corresponding \ORs\ were 1.00, 1.83, 2.81 and 5.13 across wGRS quartiles. Participants in the highest wGRS quartile had a 5.13-fold (95% confidence interval: 3.21–8.21) higher odds of \PA\ compared to those in the lowest quartile. Although the test for interaction was not significant, the odds of \PA\ was substantially elevated for preeclamptics with the highest wGRS quartile (OR = 14.44, 95%CI: 6.62–31.53) compared to normotensive women in the lowest wGRS quartile. Discussion Genetic variants in circadian rhythm genes may be associated with \PA\ risk. Larger studies are needed to corroborate these findings and to further elucidate the pathogenesis of this important obstetrical complication.