Mohammad Salahuddin, Bussu Giorgia, Rukh Gull, Schiöth Helgi B, Mwinyi Jessica
Functional Pharmacology and Neuroscience Unit, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
Development and Neurodiversity Lab, Department of Psychology, Uppsala University, Uppsala, Sweden.
Cephalalgia. 2025 Jan;45(1):3331024241312666. doi: 10.1177/03331024241312666.
Individuals with autism spectrum disorder (ASD) experience a wide array of neurological, psychiatric and medical comorbidities, yet little attention has been given to the potential link between ASD and migraine, one of the most prevalent neurological disorders worldwide. This study aimed to investigate whether a genetic predisposition for ASD is linked to migraine and its major subtypes, with and without aura. Additionally, potential moderator and mediators of the association between ASD and migraine were explored.
Polygenic scores (PGS) for ASD were constructed based on the genome-wide association study by the Psychiatric Genomics Consortium, on the UK Biobank cohort dataset comprising 337,386 participants using PRSice-2. Regression analyses were performed to investigate the association of ASD PGS with migraine and its major subtypes, with and without aura. Sex was explored as a potential moderating factor. The mediation analyses took into consideration variables such as education, personality trait neuroticism, body mass index (BMI) and four categories of comorbidities (psychiatric, vascular, neurologic and others).
ASD PGS were significantly and positively associated with migraine (odds ratio (OR) = 1.04, 95% confidence interval (CI) = 1.02-1.05, < 0.002), migraine without aura (OR = 1.05, 95% CI = 1.02-1.07, < 0.002) and migraine with aura (OR = 1.05, 95% CI = 1.02-1.07, < 0.002). No moderating effect of sex on the association between ASD PGS and migraine was observed. As for potential mediators, only the personality trait neuroticism significantly mediated the association between ASD PGS and migraine, with the proportion of effect mediated 8.75% (95% CI = 4-18%).
Our study suggests that individuals genetically predisposed to autism are at higher risk of experiencing migraine, including the two major subtypes, with and without aura. While emphasizing the complex shared genetic and pathophysiological interactions of these conditions, the role of personality trait neuroticism as a mediator of this relationship is highlighted.
自闭症谱系障碍（ASD）患者存在多种神经、精神和医学合并症，但ASD与偏头痛（全球最常见的神经疾病之一）之间的潜在联系却很少受到关注。本研究旨在调查ASD的遗传易感性是否与偏头痛及其主要亚型（有无先兆）有关。此外，还探讨了ASD与偏头痛之间关联的潜在调节因素和中介因素。
基于精神病基因组学联盟的全基因组关联研究，利用PRSice-2在包含337386名参与者的英国生物银行队列数据集上构建ASD的多基因评分（PGS）。进行回归分析以研究ASD PGS与偏头痛及其主要亚型（有无先兆）之间的关联。将性别作为潜在的调节因素进行探讨。中介分析考虑了教育、人格特质神经质、体重指数（BMI）和四类合并症（精神、血管、神经和其他）等变量。
ASD PGS与偏头痛（优势比（OR）=1.04，95%置信区间（CI）=1.02-1.05，<0.002）、无先兆偏头痛（OR=1.05，95%CI=1.02-1.07，<0.002）和有先兆偏头痛（OR=1.05，95%CI=1.02-1.07，<0.002）均呈显著正相关。未观察到性别对ASD PGS与偏头痛之间关联的调节作用。至于潜在的中介因素，只有人格特质神经质显著介导了ASD PGS与偏头痛之间的关联，效应介导比例为8.75%（95%CI=4-18%）。
我们的研究表明，具有自闭症遗传易感性的个体患偏头痛的风险更高，包括有无先兆这两种主要亚型。在强调这些疾病复杂的共同遗传和病理生理相互作用的同时，突出了人格特质神经质作为这种关系中介的作用。
