Genome-Wide Association Analyses in Family Triads and Dyads Following Assisted Reproductive Technology

Abstract

Genetic selection occurs at different stages before a successful birth. The genetic makeup of a couple may influence the likelihood of needing assisted reproductive technology (ART) to achieve conception. However, frequent early fetal losses may also be perceived as reduced couple fertility and may thus be a contributing factor to the need for ART treatment. As ART procedures may enhance early fetal survival, genes that impact fetal viability may have a different allele distribution in ART offspring than expected under Mendelian transmission, as well as compared with the general population. With genetic data available from the Norwegian Mother, Father, and Child Cohort Study, we defined fetal survival as the study outcome and analyzed 1336 case-parent triads and dyads where the offspring were conceived by ART. Using log-linear models implemented in the R package Haplin, we conducted genome-wide scans to estimate fetal, maternal, and parent-of-origin effects and provided a detailed discussion on how these effects are estimated and interpreted. We detected fetal effects for single-nucleotide polymorphisms (SNPs) located in CXXC4-AS1, OPCML, and DYNLRB2-AS1. Since these effects were not observed in a limited follow-up analysis of non-ART triads, the identified effects are unlikely caused by genetic selection before fertilization.