Department of Neurology, Danish Headache Center, Copenhagen University Hospital, Glostrup, Denmark.
23andMe, Inc, Sunnyvale, CA, USA.
Eur J Neurol. 2021 May;28(5):1726-1736. doi: 10.1111/ene.14724. Epub 2021 Jan 27.
The transition from episodic migraine to chronic migraine, migraine chronification, is usually a gradual process, which involves multiple risk factors. To date, studies of the genetic risk factors for chronic migraine have focused primarily on candidate-gene approaches using healthy individuals as controls.
In this study, we used a large cohort of migraine families and unrelated migraine patients (n > 2200) with supporting genotype and whole-genome sequencing data. We evaluated whether there are any genetic variants, common or rare, with a specific association to chronic migraine compared with episodic migraine.
We found no aggregation of chronic migraine in families with a clustering of migraine. No specific rare variants gave rise to migraine chronification, and migraine chronification was not associated with a higher polygenic risk score. Migraine chronification was not associated with allelic associations with an odds ratio above 2.65. Assessment of effect sizes with genome-wide significance below an odds ratio of 2.65 requires a genome-wide association study of at least 7500 chronic migraine patients.
Our results suggest that migraine chronification is caused by environmental factors rather than genetic factors.
从阵发性偏头痛到慢性偏头痛的转变，即偏头痛慢性化，通常是一个渐进的过程，涉及多种危险因素。迄今为止，对慢性偏头痛的遗传风险因素的研究主要集中在使用健康个体作为对照的候选基因方法上。
在这项研究中，我们使用了一个由大量偏头痛家族和无关的偏头痛患者（n＞2200）组成的队列，这些患者具有支持的基因型和全基因组测序数据。我们评估了是否存在任何常见或罕见的遗传变异与慢性偏头痛与阵发性偏头痛相比具有特定的关联。
我们没有发现偏头痛家族中偏头痛聚集与慢性偏头痛聚集之间存在关联。没有特定的罕见变异导致偏头痛慢性化，而且偏头痛慢性化与更高的多基因风险评分无关。偏头痛慢性化与等位基因关联的比值比大于 2.65 的情况没有关联。评估效应大小与全基因组显著性低于比值比 2.65 需要对至少 7500 名慢性偏头痛患者进行全基因组关联研究。
我们的结果表明，偏头痛慢性化是由环境因素而非遗传因素引起的。
