E. Kapiainen, M. K. Karjalainen, P. B. Petrov, R. K. Arffman, U. Saarela, S. E. Parks, FinnGen, E. Trichia, D. Aguilar-Ramirez, L. Luyckx, M. Myllykangas, J. M. Torres, J. Berumen, J. Alegre-Diaz, P. Kuri-Morales, R. Tapia Conyer, L. C. Cuello, R. P. Masand, K. Pylkäs, L. Lehtiö, D. Monsivais, T. T. Piltonen, J. Kettunen, R. Prunskaite-Hyyryläinen
Reproduction is one of the most fundamental biological processes in the human body, yet the molecules governing it remain incompletely understood. Here, we have characterized the role of PKHD1L1 and its globally relatively common splice donor variant rs17368310 in female fertility. We demonstrate estrogen-responsive expression of PKHD1L1 in the human endometrial and Fallopian tube epithelium, identify the change in the rs17368310 mRNA sequence in endometrial tissue, and assess the possible effects of the variant on the PKHD1L1 protein through structural modeling. We reveal that women homozygous for rs17368310 have a persistently lower child count compared to other genotypes not only among all women but also among women who have undergone medical treatments for infertility in the Finnish population. We further show that rs17368310 associates with female infertility-related traits also in the Mexican population. These findings elucidate the effects of rs17368310 on fertility in millions of reproductive-age women across different populations.