Pregnancy does not modify the risk of MS in genetically susceptible women.
Pregnancy does not modify the risk of MS in genetically susceptible women.
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DOI：
10.1212/nxi.0000000000000898
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发表时间：
2020-11
期刊：
影响因子：
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通讯作者：
Barcellos LF
中科院分区：
文献类型：
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作者：
Adams CJ;Wu SL;Shao X;Bradshaw PT;Gonzales E;Smith JB;Xiang AH;Bellesis KH;Chinn T;Bos SD;Wendel-Haga M;Olsson T;Kockum I;Langer-Gould AM;Schaefer C;Alfredsson L;Barcellos LF
采用病例-基因-环境（GE）相互作用研究设计，评估白色成年女性MS症状发作前妊娠与MS已确定遗传危险因素之间的相互作用。我们研究了来自美国，瑞典和挪威4个队列的2，497例女性MS病例的临床，生殖和遗传数据。妊娠暴露定义为2种方式：（1）MS症状发作前的活产妊娠和（2）MS症状发作前的产次。我们在每个队列中使用logistic回归和比例优势回归估计了妊娠暴露与已建立的遗传风险变体之间的相互作用，包括加权遗传风险评分以及HLA和非HLA变体。使用随机效应的逆方差荟萃分析将队列内相关性合并。在7，067名无MS的个体中测试了仅病例G × E独立性假设。未观察到妊娠暴露与已确定的遗传风险变体（包括强相关的HLA-DRB 1 *15：01等位基因和加权遗传风险评分）之间相互作用的证据。敏感性分析的结果与观察结果一致。我们的研究结果表明，症状发作前怀孕并不改变遗传易感的白色女性MS的风险。
To use the case-only gene-environment (G 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) 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 HLA-DRB1*15:01 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.