Association Between Insomnia and Migraine Risk: A Case–Control and Bidirectional Mendelian Randomization Study

Chu, Shujuan; Wu, Zhilin; Wu, Zhouyang; Wu, Jing; Ye, Qian

doi:10.2147/pgpm.s305780

Cited by 15 publications

(11 citation statements)

References 41 publications

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“…There is genetic overlap between several sleep traits and migraine. 51 Moreover, insomnia is a risk factor for the development of migraine, 52,53 raising the question whether the circadian features of insomnia genes 54 are also relevant in migraine.…”

Section: Discussionmentioning

confidence: 99%

Circadian Features of Cluster Headache and Migraine

et al. 2023

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Background and objectives:Cluster headache and migraine have circadian features at multiple levels (cellular, systems, and behavioral). A thorough understanding of their circadian features informs their pathophysiologies.Methods:A librarian created search criteria in Medline Ovid, Embase, PsycINFO, Web of Science, and Cochrane Library. Two physicians independently performed the remainder of the systematic review/meta-analysis using PRISMA guidelines. Separate from the systematic review/meta-analysis we performed a genetic analysis for genes with a circadian pattern of expression (Clock Controlled Genes or CCGs) by cross-referencing genome-wide association studies (GWAS) of headache, a non-human primate study of CCGs in a variety of tissues, and recent reviews of brain areas relevant in headache disorders. Altogether, this allowed us to catalog circadian features at the behavioral level (circadian timing, time of day, time of year, and chronotype), systems level (relevant brain areas where CCGs are active, melatonin and corticosteroid levels), and cellular level (core circadian genes and CCGs).Results:For the systematic review and meta-analysis, 1513 studies were found and 72 met inclusion criteria; for the genetic analysis we found 16 GWAS, 1 non-human primate study, and 16 imaging reviews.Cluster headache:Behaviorally, meta-analyses showed a circadian pattern of attacks in 70.5% (3490/4953) of participants across 16 studies, with a clear circadian peak between 21:00-03:00 and circannual peaks in spring and autumn. Chronotype was highly variable across studies. At the systems level, lower melatonin and higher cortisol levels were reported. At the cellular level, cluster headache was associated with core circadian genesCLOCKandREV-ERBα, and five of the nine cluster headache susceptibility genes were CCGs.Migraine:Behaviorally, meta-analyses showed a circadian pattern of attacks in 50.1% (2698/5385) of participants across eight studies, with a clear circadian trough between 23:00-07:00 and a broad circannual peak between April-October. Chronotype was highly variable across studies. At the systems level, urinary melatonin levels were lower in migraine participants and even lower during an attack. At the cellular level, migraine was associated with core circadian genesCK1δandRORα, and 110 of the 168 migraine susceptibility genes were CCGs.Discussion:Cluster headache and migraine are highly circadian at multiple levels, reinforcing the importance of the hypothalamus. This review provides a pathophysiological foundation for circadian-targeted research into these disorders.Trial Registration Information:The study was registered with PROSPERO (registration number CRD42021234238).

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Section: Discussionmentioning

confidence: 99%

Circadian Features of Cluster Headache and Migraine

et al. 2023

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“…It seems that not all epidemiological link can be confirmed by MR study. A case in point is that most epidemiological data believed that there is a bidirectional causal relationship between insomnia and migraine, only a one-way link has been established by MR study, namely that genetically predicted insomnia is the risk for migraine [36]. In future studies, the causal associations between allergic disease, asthma, and insomnia need to be further explored by MR studies with larger GWAS samples.…”

Section: Discussionmentioning

confidence: 99%

Exploring genetic association of insomnia with allergic disease and asthma: a bidirectional Mendelian randomization study

Chen

Zhao

et al. 2022

Respir Res

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Background Insomnia is highly prevalent among patients with allergic disease and asthma; however, few studies have investigated their causal relationship. We aim to explore the causal association between insomnia and allergic disease/asthma by performing bidirectional Mendelian randomization (MR) study. Methods Instrumental variables were constructed using single nucleotide polymorphisms (SNPs). Summary statistics for insomnia, allergic disease, and asthma were obtained from four large-scale genome-wide association studies (GWAS) of European ancestry. The pleiotropy analysis was applied by using the MR-Egger intercept test and the MR pleiotropy residual sum and outlier (MR-PRESSO) test. MR analyses were conducted by using inverse variance weighted (IVW), weighted median, and MR-Egger method. Results Based on the multiplicative random effects IVW method, the MR analysis showed that genetically predicted insomnia was causally associated with an increased risk of allergic disease [odds ratio (OR) = 1.054, 95% confidence interval (CI) = 1.031–1.078, P = 3.817 × 10–06], asthma (OR = 1.043, 95% CI = 1.010–1.077, P = 9.811 × 10–03), moderate-severe asthma (OR = 1.168, 95% CI = 1.069–1.277, P = 6.234 × 10–04), and adult-onset asthma (OR = 1.086, 95% CI = 1.037–1.138, P = 4.922 × 10–04). In bidirectional analyses, we did not find evidence supporting the reverse causality relations. Conclusions Our MR study suggested that genetically predicted insomnia was the risk factor for allergic disease and asthma. Improving sleep quality could be one of the cornerstones in the prevention of allergic disease and asthma.

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“…In addition, liability to migraine leads to an increased coronary artery disease risk (99). Third, two studies explored the relationship with sleep-related comorbidities and provided evidence for a significant causal effect of difficulty awakening (OR [95% CI] = 1.37 [1.12–1.68], P = 0.002) (81) and insomnia (OR [95% CI] = 1.24 [1.11–1.38], P = 1.01 × 10 −4 ) (100) on the risk of migraine. Fourth, various MRs exploring behavioural traits, such as smoking, alcohol and coffee consumption, have shown that a higher alcohol or coffee consumption leads to a reduced migraine risk (101).…”

Section: Causality In Migrainementioning

confidence: 99%

Migraine genetics: Status and road forward

et al. 2023

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Background Migraine is considered a multifactorial genetic disorder. Different platforms and methods are used to unravel the genetic basis of migraine. Initially, linkage analysis in multigenerational families followed by Sanger sequencing of protein-coding parts (exons) of genes in the genomic region shared by affected family members identified high-effect risk DNA mutations for rare Mendelian forms of migraine, foremost hemiplegic migraine. More recently, genome-wide association studies testing millions of DNA variants in large groups of patients and controls have proven successful in identifying many dozens of low-effect risk DNA variants for the more common forms of migraine with the number of associated DNA variants increasing steadily with larger sample sizes. Currently, next-generation sequencing, utilising whole exome and whole genome sequence data, and other omics data are being used to facilitate their functional interpretation and the discovery of additional risk factors. Various methods and analysis tools, such as genetic correlation and causality analysis, are used to further characterise genetic risk factors. Findings We describe recent findings in genome-wide association studies and next-generation sequencing analysis in migraine. We show that the combined results of the two most recent and most powerful migraine genome-wide association studies have identified a total of 178 LD-independent ( r2 < 0.1) genome-wide significant single nucleotide polymorphisms (SNPs), of which 99 were unique to Hautakangas et al., 11 were unique to Choquet et al., and 68 were identified by both studies. When considering that Choquet et al. also identified three SNPs in a female-specific genome-wide association studies then these two recent studies identified 181 independent SNPs robustly associated with migraine. Cross-trait and causal analyses are beginning to identify and characterise specific biological factors that contribute to migraine risk and its comorbid conditions. Conclusion This review provides a timely update and overview of recent genetic findings in migraine.

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Association Between Insomnia and Migraine Risk: A Case–Control and Bidirectional Mendelian Randomization Study

Cited by 15 publications

References 41 publications

Circadian Features of Cluster Headache and Migraine

Circadian Features of Cluster Headache and Migraine

Exploring genetic association of insomnia with allergic disease and asthma: a bidirectional Mendelian randomization study

Migraine genetics: Status and road forward

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