Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
Mult Scler. 2024 Jul;30(8):994-1003. doi: 10.1177/13524585241257205. Epub 2024 Jun 7.
Previous investigations into multiple sclerosis (MS) risk factors predominantly relied on retrospective studies, which do not consider different follow-up times and assume a constant risk effect throughout lifetime.
We aimed to evaluate the impact of genetic and early life factors on MS diagnosis by employing a time-to-event analysis in a prospective cohort.
We used the UK Biobank data, considering the observation period from birth up to 31 December 2022. We considered genetic risk, using a multiple sclerosis polygenic risk score (MS-PRS), and various early life factors. Tobacco smoking and infectious mononucleosis diagnosis were also considered as time-varying variables along the follow-up. Using a Cox proportional hazards model, we examined the associations between these factors and MS diagnosis instantaneous risk.
We analyzed 345,027 participants, of which 1669 had an MS diagnosis. Our analysis revealed age-dependent effects for sex (females vs males) and higher MS-PRS, with greater hazard ratios observed in young adults.
The age-dependent effects suggest that retrospective studies could have underestimated sex and genetic variants' risk roles during younger ages. Therefore, we emphasize the importance of a time-to-event approach using longitudinal data to better characterize age-dependent risk effects.
先前对多发性硬化症 (MS) 危险因素的研究主要依赖于回顾性研究，这些研究没有考虑到不同的随访时间，并假设终生风险效应是恒定的。
我们旨在通过在前瞻性队列中进行事件时间分析来评估遗传和早期生活因素对 MS 诊断的影响。
我们使用英国生物库数据，考虑从出生到 2022 年 12 月 31 日的观察期。我们使用多发性硬化症多基因风险评分 (MS-PRS) 来考虑遗传风险，并考虑了各种早期生活因素。吸烟和传染性单核细胞增多症的诊断也被视为随访过程中的时变变量。使用 Cox 比例风险模型，我们检查了这些因素与 MS 诊断即时风险之间的关联。
我们分析了 345027 名参与者，其中 1669 人被诊断为 MS。我们的分析显示，性别（女性与男性）和更高的 MS-PRS 存在年龄依赖性效应，在年轻成年人中观察到更高的危险比。
年龄依赖性效应表明，回顾性研究可能低估了年轻时性别和遗传变异的风险作用。因此，我们强调使用纵向数据进行事件时间分析的重要性，以更好地描述年龄依赖性风险效应。
