Maternal Genetic Variants and Gestational Duration: A Replication Study in a Japanese Cohort

Background/Objectives: The objective of this study is to evaluate whether maternal genetic variants previously associated with gestational duration in European-ancestry populations are associated with gestational duration in Japanese women. Methods: We analyzed 347 women with a history of delivery from a community-based cohort in Aomori Prefecture, Japan. Gestational age at first delivery (weeks) was obtained from the Maternal and Child Health Handbook. Four representative maternal single-nucleotide polymorphisms were analyzed: rs2946169 near EBF1, rs2955117 in/near EEFSEC, rs12037376 in/near WNT4, and rs9861425 in/near ADCY5. Maternal genotype data were obtained from existing Japonica Array data generated as part of the Iwaki Health Promotion Project. Associations with gestational age at first delivery were tested using linear regression under an additive genetic model, adjusted for maternal age at first delivery. A Bonferroni-corrected threshold of p < 0.0125 was applied for four SNPs. Results: Mean gestational age at first delivery was 39.4 weeks. Each additional rs2946169 T allele was nominally associated with shorter gestation (adjusted β = -0.2679 weeks per allele; p = 0.021), but this association did not remain significant after Bonferroni correction. No significant associations were observed for rs2955117, rs12037376, or rs9861425. Conclusions: These findings provide suggestive evidence that maternal variation at the EBF1 locus may be related to gestational duration in Japanese women. However, the association did not remain significant after multiple-testing correction, and larger studies are needed to confirm this finding and clarify population-specific genetic effects.