Skodvin Siri N, Gjessing Håkon K, Jugessur Astanand, Romanowska Julia, Page Christian M, Corfield Elizabeth C, Lee Yunsung, Håberg Siri E, 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. 2023 Oct;47(7):503-519. doi: 10.1002/gepi.22534. Epub 2023 Aug 28.
Infertility is a heterogeneous phenotype, and for many couples, the causes of fertility problems remain unknown. One understudied hypothesis is that allelic interactions between the genotypes of the two parents may influence the risk of infertility. Our aim was, therefore, to investigate how allelic interactions can be modeled using parental genotype data linked to 15,789 pregnancies selected from the Norwegian Mother, Father, and Child Cohort Study. The newborns in 1304 of these pregnancies were conceived using assisted reproductive technologies (ART), and the remainder were conceived naturally. Treating the use of ART as a proxy for infertility, different parameterizations were implemented in a genome-wide screen for interaction effects between maternal and paternal alleles at the same locus. Some of the models were more similar in the way they were parameterized, and some produced similar results when implemented on a genome-wide scale. The results showed near-significant interaction effects in genes relevant to the phenotype under study, such as Dynein axonemal heavy chain 17 (DNAH17) with a recognized role in male infertility. More generally, the interaction models presented here are readily adaptable to the study of other phenotypes in which maternal and paternal allelic interactions are likely to be involved.
不孕症是一种异质性表型，对于许多夫妇来说，生育问题的原因仍然不明。一个研究较少的假说是，父母双方基因型之间的等位基因相互作用可能会影响不孕风险。因此，我们的目的是研究如何利用与从挪威母亲、父亲和儿童队列研究中选取的15789例妊娠相关的父母基因型数据来构建等位基因相互作用模型。这些妊娠中有1304例的新生儿是通过辅助生殖技术（ART）受孕的，其余的是自然受孕。将ART的使用作为不孕症的一个替代指标，在全基因组范围内筛选同一基因座上母本和父本等位基因之间的相互作用效应时，采用了不同的参数设置。有些模型在参数设置方式上更为相似，有些在全基因组范围内实施时产生了相似的结果。结果显示，在所研究的表型相关基因中存在接近显著的相互作用效应，例如动力蛋白轴丝重链17（DNAH17），它在男性不育中具有公认的作用。更一般地说，这里提出的相互作用模型很容易适用于其他可能涉及母本和父本等位基因相互作用的表型研究。
