Skodvin Siri N, Gjessing Håkon K, Jugessur Astanand, Romanowska Julia, Havdahl Alexandra, Håberg Siri E, Hanevik Hans Ivar, Lyle Robert, Lie Rolv Terje, Gjerdevik Miriam
Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway.
Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.
Genet Epidemiol. 2025 Jul;49(5):e70011. doi: 10.1002/gepi.70011.
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.
基因选择发生在成功分娩前的不同阶段。夫妻的基因构成可能会影响通过辅助生殖技术（ART）实现受孕的可能性。然而，早期频繁的胎儿丢失也可能被视为夫妻生育能力下降，因此可能是需要进行ART治疗的一个因素。由于ART程序可能会提高早期胎儿的存活率，影响胎儿生存能力的基因在ART后代中的等位基因分布可能与孟德尔遗传预期不同，也与普通人群不同。利用挪威母婴队列研究的基因数据，我们将胎儿存活定义为研究结果，并分析了1336个病例-父母三联体和二联体，其中后代是通过ART受孕的。使用R包Haplin中实现的对数线性模型，我们进行了全基因组扫描，以估计胎儿、母亲和源自父母的效应，并详细讨论了如何估计和解释这些效应。我们检测到位于CXXC4-AS1、OPCML和DYNLRB2-AS1中的单核苷酸多态性（SNP）的胎儿效应。由于在对非ART三联体的有限随访分析中未观察到这些效应，因此所确定的效应不太可能是由受精前的基因选择引起的。
