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Migraine and its major subtypes: with and without aura are associated with polygenic scores for autism
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Funktionell farmakologi och neurovetenskap.ORCID-id: 0000-0002-6050-4708
Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi. (Development and Neurodiversity Lab)ORCID-id: 0000-0002-6071-3964
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Funktionell farmakologi och neurovetenskap.ORCID-id: 0000-0003-0000-7694
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Funktionell farmakologi och neurovetenskap.ORCID-id: 0000-0001-7112-0921
Visa övriga samt affilieringar
2025 (Engelska)Ingår i: Cephalalgia, ISSN 0333-1024, E-ISSN 1468-2982, Vol. 45, nr 1, s. 1-12Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Background

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.

Methods

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).

Results

ASD PGS were significantly and positively associated with migraine (odds ratio (OR) = 1.04, 95% confidence interval (CI) = 1.02–1.05, p < 0.002), migraine without aura (OR = 1.05, 95% CI = 1.02–1.07, p < 0.002) and migraine with aura (OR = 1.05, 95% CI = 1.02–1.07, p < 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%).

Conclusions

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.

Ort, förlag, år, upplaga, sidor
Sage Publications, 2025. Vol. 45, nr 1, s. 1-12
Nyckelord [en]
aura, autism, headache, migraine, polygenic risk score
Nationell ämneskategori
Neurovetenskaper
Identifikatorer
URN: urn:nbn:se:uu:diva-537908DOI: 10.1177/03331024241312666ISI: 001411832200005Scopus ID: 2-s2.0-85215995515OAI: oai:DiVA.org:uu-537908DiVA, id: diva2:1895609
Forskningsfinansiär
Svenska Sällskapet för Medicinsk Forskning (SSMF)Tillgänglig från: 2024-09-06 Skapad: 2024-09-06 Senast uppdaterad: 2025-02-20Bibliografiskt granskad
Ingår i avhandling
1. Deciphering Adult Autism: Exploring Polygenic Risk, Brain Structure, Well-being, Migraine, and Mental Health Disorders
Öppna denna publikation i ny flik eller fönster >>Deciphering Adult Autism: Exploring Polygenic Risk, Brain Structure, Well-being, Migraine, and Mental Health Disorders
2024 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

This research work comprises four studies investigating mental health disorders, with a particular focus on Autism Spectrum Disorder (ASD, hereafter referred to as autism). The research integrates epidemiological perspectives and genetic frameworks to explore connections with well-being, conditions such as migraine, and neuroanatomical brain structure changes in adulthood, utilizing data from the large European population cohort, UK Biobank, with over half a million participants.

Paper I examined the relationship between job satisfaction, job tenure, and 16 self-reported physician posed diagnosed mental health conditions. The findings show that Neurotic & Stress Disorders, Eating Disorders, and Other Mental Health Disorders are strongly associated with lower job satisfaction and shorter job tenure, highlighting the impact of mental health on workplace participation. Personality trait neuroticism significantly influences job satisfaction but not job tenure.

Paper II explored the relationship between genetic predispositions for autism and five well-being traits (neuroticism, depression, loneliness, life satisfaction, and positive affect). Polygenic risk scores (PRS) for autism were significantly associated with decreased well-being, particularly an increased risk of negative traits such as neuroticism and depression, and reduced positive traits such as life satisfaction, highlighting the genetic basis of well-being in individuals with autism.

Paper III examined the genetic link between autism and migraine, revealing that individuals with a genetic predisposition for autism have an increased risk of migraine, including both major types, migraine with and without aura. While no moderating effect of sex was found, personality trait neuroticism significantly mediated the relationship between autism and migraine, emphasizing the complex genetic and pathophysiological connections between autism and migraine, with neuroticism playing a key role in mediating this association.

Paper IV investigated the association between autism polygenic risk scores and brain volume alterations in the cerebellum, brainstem, and global brain structures in adults. The results demonstrated significant correlations, with higher autism PRS linked to reduced brain volumes, particularly in the cerebellum and brainstem, highlighting the genetic influence on neuroanatomical changes in autism adulthood.

These studies highlight the intricate connections between mental health, genetics, and brain structure, offering valuable insights for improving workplace participation and well-being in individuals with mental health issues including autism.

Ort, förlag, år, upplaga, sidor
Uppsala: Acta Universitatis Upsaliensis, 2024. s. 38
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 2074
Nyckelord
Genetic risk score, mental health disorder, autism, migraine, well-being, MRI, brain
Nationell ämneskategori
Neurovetenskaper
Forskningsämne
Molekylär biovetenskap; Bioinformatik; Medicinsk vetenskap
Identifikatorer
urn:nbn:se:uu:diva-537917 (URN)978-91-513-2225-4 (ISBN)
Disputation
2024-10-25, room A1:111a, Uppsala biomedicinska centrum (BMC), Husargatan 3, Uppsala, 10:00 (Engelska)
Opponent
Handledare
Tillgänglig från: 2024-10-02 Skapad: 2024-09-06 Senast uppdaterad: 2024-10-02

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Mohammad, SalahuddinBussu, GiorgiaRukh, GullSchiöth, Helgi B.Mwinyi, Jessica

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Mohammad, SalahuddinBussu, GiorgiaRukh, GullSchiöth, Helgi B.Mwinyi, Jessica
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Funktionell farmakologi och neurovetenskapInstitutionen för psykologi
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Cephalalgia
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