Yuan Jiang, Carolyn E Cesta, Qianwen Liu, Elaine Kingwell, Pernilla Stridh, Klementy Shchetynsky, Tomas Olsson, Ingrid Kockum, Elisabet Stener-Victorin, Xia Jiang, Ali Manouchehrinia
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The genome-wide cross-trait analysis examined the genetic architecture.</p><p><strong>Results: </strong>In a Swedish cohort of 1,374,529 women, 77 (0.3%) with PCOS and 3,654 (0.3%) without PCOS were diagnosed with MS. After adjusting for birth year and obesity, no association was found between PCOS and MS (<i>HR</i> = 0.91, 95% CI = 0.72-1.15), which was confirmed by Mendelian randomization analysis, where genetically predicted PCOS propensity, sex hormone-binding globulin (SHBG), or testosterone levels did not causally affect MS risk (all <i>p</i>-values > 0.05). By exploring horizontal pleiotropy, we identified shared genetic regions and 19 independent pleiotropic SNPs for SHBG with MS and 11 for testosterone with MS.</p><p><strong>Conclusion: </strong>We did not find evidence for a causal role of PCOS, as a proxy of elevated testosterone, in reducing the risk of MS in women. 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引用次数: 0
摘要
背景:女性罹患多发性硬化症(MS)的风险较高,这可能与荷尔蒙因素有关。多囊卵巢综合征(PCOS)中常见的睾酮水平升高可能会影响多发性硬化症的风险:目的:通过表型和基因组分析,研究多囊卵巢综合征(睾酮水平升高的替代指标)与多发性硬化症风险之间的关系:Cox回归模型分析了多囊卵巢综合征与多发性硬化症风险之间的关系。全基因组跨性状分析研究了遗传结构:结果:在瑞典的 1,374,529 名女性队列中,77 名(0.3%)患有多囊卵巢综合征的女性和 3,654 名(0.3%)未患有多囊卵巢综合征的女性被诊断为多发性硬化症。在对出生年份和肥胖进行调整后,未发现多囊卵巢综合征与多发性硬化症之间有任何关联(HR = 0.91,95% CI = 0.72-1.15),孟德尔随机分析证实了这一点,其中基因预测的多囊卵巢综合征倾向、性激素结合球蛋白(SHBG)或睾酮水平不会对多发性硬化症风险产生因果影响(所有 p 值均大于 0.05)。通过探索水平多效性,我们发现了SHBG与多发性硬化症的共有遗传区域和19个独立多效性SNPs,以及睾酮与多发性硬化症的11个独立多效性SNPs:结论:我们没有发现证据表明多囊卵巢综合征(睾酮升高的代表)在降低女性罹患 MS 风险方面起着因果作用。睾酮、SHBG 和多发性硬化之间的共同遗传位点提供了生物学见解。
Exploring the relationship between polycystic ovarian syndrome, testosterone, and multiple sclerosis in women: A nationwide cohort study and genome-wide cross-trait analysis.
Background: Women have a higher risk of developing multiple sclerosis (MS), potentially due to hormonal factors. Elevated testosterone levels, common in polycystic ovary syndrome (PCOS), might influence MS risk.
Objective: To investigate the relationship between PCOS, as a proxy for elevated testosterone levels, and MS risk through phenotypic and genomic analysis.
Methods: Cox regression models analysed the association between PCOS and MS risk. The genome-wide cross-trait analysis examined the genetic architecture.
Results: In a Swedish cohort of 1,374,529 women, 77 (0.3%) with PCOS and 3,654 (0.3%) without PCOS were diagnosed with MS. After adjusting for birth year and obesity, no association was found between PCOS and MS (HR = 0.91, 95% CI = 0.72-1.15), which was confirmed by Mendelian randomization analysis, where genetically predicted PCOS propensity, sex hormone-binding globulin (SHBG), or testosterone levels did not causally affect MS risk (all p-values > 0.05). By exploring horizontal pleiotropy, we identified shared genetic regions and 19 independent pleiotropic SNPs for SHBG with MS and 11 for testosterone with MS.
Conclusion: We did not find evidence for a causal role of PCOS, as a proxy of elevated testosterone, in reducing the risk of MS in women. The shared genetic loci between testosterone, SHBG, and MS provide biological insights.
期刊介绍:
Multiple Sclerosis Journal is a peer-reviewed international journal that focuses on all aspects of multiple sclerosis, neuromyelitis optica and other related autoimmune diseases of the central nervous system.
The journal for your research in the following areas:
* __Biologic basis:__ pathology, myelin biology, pathophysiology of the blood/brain barrier, axo-glial pathobiology, remyelination, virology and microbiome, immunology, proteomics
* __Epidemology and genetics:__ genetics epigenetics, epidemiology
* __Clinical and Neuroimaging:__ clinical neurology, biomarkers, neuroimaging and clinical outcome measures
* __Therapeutics and rehabilitation:__ therapeutics, rehabilitation, psychology, neuroplasticity, neuroprotection, and systematic management
Print ISSN: 1352-4585