From the Divisions of Epidemiology and Biostatistics (C.J.A., S.L.W.), School of Public Health, University of California, Berkeley, Berkeley, CA; Genetic Epidemiology and Genomics Laboratory (X.S., L.F.B.), University of California, Berkeley, Berkeley, CA; School of Public Health (P.T.B.), University of California, Berkeley, Berkeley, CA, USA; Department of Research & Evaluation (E.G., J.B.S., A.H.X.), Kaiser Permanente Southern California, Los Angeles, CA; Kaiser Permanente Division of Research (K.H.B., T.C., C.S.), Kaiser Permanente Northern California, Oakland, CA; University of Oslo (S.D.B.), Institute of Clinical Medicine & Oslo University Hospital, Department of Neurology, Oslo, Norway; Oslo University Hospital (M.W.-H.), Department of Neurology, Oslo, Norway; Department of Clinical Neuroscience (T.O.), Karolinska Instituet, Stockholm, Sweden; Department of Clinical Neuroscience (I.K.), Karolinska Institutet, Stockholm, Sweden; Southern California Permanente Medical Group/Kaiser Permanente (A.M.L.-G.), Department of Neurology, Los Angeles, CA; and Institute of Environmental Medicine (L.A.), Karolinska Institutet and Centre for Occupational and Environmental Medicine, Region Stockholm, Stockholm, Sweden.
Neurol Neuroimmunol Neuroinflamm. 2020 Oct 9;7(6). doi: 10.1212/NXI.0000000000000898. Print 2020 Nov.
To use the case-only gene-environment (G [Formula: see text] E) interaction study design to estimate interaction between pregnancy before onset of MS symptoms and established genetic risk factors for MS among White adult females.
We studied 2,497 female MS cases from 4 cohorts in the United States, Sweden, and Norway with clinical, reproductive, and genetic data. Pregnancy exposure was defined in 2 ways: (1) [Formula: see text] live birth pregnancy before onset of MS symptoms and (2) parity before onset of MS symptoms. We estimated interaction between pregnancy exposure and established genetic risk variants, including a weighted genetic risk score and both HLA and non-HLA variants, using logistic regression and proportional odds regression within each cohort. Within-cohort associations were combined using inverse variance meta-analyses with random effects. The case-only G × E independence assumption was tested in 7,067 individuals without MS.
Evidence for interaction between pregnancy exposure and established genetic risk variants, including the strongly associated allele and a weighted genetic risk score, was not observed. Results from sensitivity analyses were consistent with observed results.
Our findings indicate that pregnancy before symptom onset does not modify the risk of MS in genetically susceptible White females.
利用病例-only 基因-环境（G×E）交互研究设计，估计白种成年女性中 MS 症状发作前的妊娠与 MS 既定遗传风险因素之间的交互作用。
我们研究了来自美国、瑞典和挪威的 4 个队列的 2497 名女性 MS 病例，这些队列具有临床、生殖和遗传数据。妊娠暴露以两种方式定义：（1）MS 症状发作前的[Formula: see text]活产妊娠，（2）MS 症状发作前的生育次数。我们使用逻辑回归和比例优势回归在每个队列内估计妊娠暴露与既定遗传风险变异之间的交互作用，包括加权遗传风险评分以及 HLA 和非 HLA 变异。使用随机效应的逆方差荟萃分析合并队列内的关联。在没有 MS 的 7067 个人中测试了病例-only G×E 独立性假设。
没有观察到妊娠暴露与既定遗传风险变异之间的交互作用的证据，包括强烈相关的 等位基因和加权遗传风险评分。敏感性分析的结果与观察到的结果一致。
我们的研究结果表明，MS 症状发作前的妊娠并不能改变易感白种女性的 MS 风险。
