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.