Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA.
Prenat Diagn. 2021 Apr;41(5):591-609. doi: 10.1002/pd.5919. Epub 2021 Mar 16.
In our previous work, we performed the first genome-wide association study to find genetic risk factors for maternal nondisjunction of chromosome 21. The objective of the current work was to perform stratified analyses of the same dataset to further elucidate potential mechanisms of genetic risk factors.
We focused on loci that were statistically significantly associated with maternal nondisjunction based on this same dataset in our previous study and performed stratified association analyses in seven subgroups defined by age and meiotic recombination profile. In each analysis, we contrasted a different subgroup of mothers with the same set of fathers, the mothers serving as cases (phenotype: meiotic nondisjunction of chromosome 21) and the fathers as controls.
Our stratified analyses identified several genes whose patterns of association are consistent with generalized effects across groups, as well as other genes that are consistent with specific effects in certain groups.
While our results are epidemiological in nature and cannot conclusively prove mechanisms, we identified a number of patterns that are consistent with specific mechanisms. In many cases those mechanisms are strongly supported by available literature on the associated genes.
在我们之前的工作中，我们进行了首次全基因组关联研究，以寻找导致 21 号染色体母源性非分离的遗传风险因素。本研究的目的是对同一数据集进行分层分析，以进一步阐明遗传风险因素的潜在机制。
我们根据之前研究中的同一数据集，重点分析了与母源性非分离在统计学上显著相关的基因座，并在七个由年龄和减数分裂重组谱定义的亚组中进行了分层关联分析。在每次分析中，我们都将不同的亚组母亲与同一组父亲进行对比，母亲作为病例（表型：21 号染色体减数分裂非分离），而父亲作为对照。
我们的分层分析确定了几个基因，它们的关联模式与各群体的普遍效应一致，还有一些基因与某些群体的特定效应一致。
虽然我们的结果具有流行病学性质，不能确定地证明机制，但我们确定了一些与特定机制一致的模式。在许多情况下，这些机制得到了相关基因的现有文献的有力支持。
