Whole-exome sequencing reveals novel variants associated with abnormal uterine bleeding caused by copper intrauterine device Supplementary Materials

Aim: This study aimed to explore the genetic risk factors and validate variants of abnormal uterine
bleeding after copper intrauterine device insertion. Methods: Whole-exome sequencing was performed
and several variants were validated by Sequenom MassARRAY. Results: Eight variants showed potential
clinical damage according to American College of Medical Genetics and Genomics criteria. By combined
analysis of screening and validation, NFASC RS2802808 C>G p.Ile971Met (Pallele = 0.009 and Pgenotype = 0.027)
and PIGR RS2275531 C>T p.Gly365Ser (Pallele = 0.009 and Pgenotype = 0.013) variants were identified
as significantly associated with abnormal uterine bleeding with a false discovery rate <0.05. NFASC
and PIGR may play a role in abnormal uterine bleeding by regulating coagulation fibrinolysis and
endometrial epithelium inflammation functions. Conclusion: These findings provide a genetic basis for
clinical individualization and precision of intrauterine device implantation.