New and sex-specific migraine susceptibility loci identified from a multiethnic genome-wide meta-analysis

Choquet, Hélène; Yin, Jie; Jacobson, Alice; Horton, Brandon; Hoffmann, Thomas J.; Jorgenson, Eric; Avins, Andrew L.; Pressman, Alice

doi:10.1038/s42003-021-02356-y

Cited by 36 publications

(62 citation statements)

References 96 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We used data on genetic variants associated with migraine from the largest GWAS meta-analysis, which included 889,018 participants (85,726 migraine cases) [ 8 ]. This data set consists of the European ancestry from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort, the UK Biobank (UKB) cohort, and GWAS summary statistics data from the study by Gormley et al [ 14 ].…”

Section: Methodsmentioning

confidence: 99%

“…A majority of the previous studies concerning the relationship between migraine and stroke have been observational, leaving the relationship to be considered tenuous, with reverse causality and existing confounding factors unable to be excluded. The most recent and largest genome-wide association studies (GWAS) of migraine [ 8 ] and stroke [ 9 ] provide a new perspective and way to help determine whether migraine is an independent risk factor for stroke occurrence. The Mendelian randomization (MR) method, which employs genetic variants as instrumental variables (IVs) to infer the causality of an association, effectively overcomes bias due to confounding and reverse causality issues in observational epidemiological studies [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Migraine and Ischemic Stroke: A Mendelian Randomization Study

Shu

Zhu

et al. 2021

Neurol Ther

View full text Add to dashboard Cite

Introduction: Previous epidemiological studies have found an increased risk for ischemic stroke in patients with migraine; however, the evidence for a causal relationship between migraine and ischemic stroke is scarce. This study aims to explore the potential causal relationship between migraine and ischemic stroke and its subtypes [including large artery stroke (LAS), small vessel stroke (SVS), and cardioembolic stroke (CES)]. Methods: We used data on genetic variants associated with migraine identified from a genome-wide association study (GWAS) metaanalysis among 889,018 European ancestries. Summary data for ischemic stroke and its subtypes were obtained from the MEGASTROKE consortium including up to 438,847 participants. We performed two-sample Mendelian randomization (MR) analyses using the inversevariance-weighted method as the primary approach. The MR-Egger, weighted median, simple median, simple mode, and weighted mode methods were also conducted as sensitivity analyses to determine the robustness of our results. Results: We failed to detect statistically significant associations between migraine and ischemic stroke (OR, 0.935; 95% CI 0.851-1.027; P = 0.159) and its subtypes (LAS: OR, 0.818; 95% CI 0.692-0.967; P = 0.018) (SVS: OR, 0.935; 95% CI 0.781-1.119; P = 0.460) (CES: OR, 1.015; 95% CI 0.867-1.189; P = 0.850). The results were consistent with the sensitivity analyses. Conclusions: By conducting a series of causal inference approaches, this study supports no causal effect of migraine on ischemic stroke and its subtypes.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Migraine and Ischemic Stroke: A Mendelian Randomization Study

Shu

Zhu

et al. 2021

Neurol Ther

View full text Add to dashboard Cite

show abstract

“…Second, migraine is twice as common in females as in males. There were several sex-specific loci associated with migraine susceptibility in females but not in males (24). However, sex-specific MR analysis was not performed in our study because sex-specific GWAS was not available.…”

Section: Discussionmentioning

confidence: 91%

“…The second study was performed by Choquet et al (24). The authors undertook GWAS analysis of migraine in the Genetic Epidemiology Research in Adult Health and Aging cohort and UK biobank, (31) followed by a meta-analysis combining the two results.…”

Section: Outcome Datasetmentioning

confidence: 99%

“…Two-sample MR analyses showed increased circulating 25OHD levels were suggestively associated with decreased migraine risk by using migraine GWASs from Choquet et al (24) and FinnGen study separately (Figure 2). The ORs based on IVW method were 0.902 (95% CI = 0.825-0.986, p = 0.023) and 0.880 (95% CI = 0.786-0.984, p = 0.025), respectively.…”

Section: Any Migrainementioning

confidence: 99%

See 1 more Smart Citation

Higher Circulating Vitamin D Levels Are Associated With Decreased Migraine Risk: A Mendelian Randomization Study

Niu

Wang

2022

Front. Nutr.

View full text Add to dashboard Cite

BackgroundEvidence showed the supplementation of vitamin D might have beneficial effects for migraine patients. We aimed to investigate the causal effects of serum vitamin D levels on migraine risk using two-sample Mendelian randomization (MR) method.MethodsA total of 184 independent genetic instruments for serum vitamin D levels were selected from a study in 417,580 Europeans from UK biobank. Six variants from an independent study were obtained to perform replication analysis. Summary-level data for migraine were obtained from three studies with 48,975 migraine cases, 28,852 migraine cases and 10,536 migraine cases, respectively.ResultsThe estimated odds ratios (ORs) per standard deviation increase in circulating vitamin D levels based on the three migraine datasets were 0.948 (95% CI = 0.883–1.016, p = 0.133), 0.902 (95% confidence intervals [CI] = 0.825–0.986, p = 0.023), and 0.880 (95% CI = 0.786–0.984, p = 0.025), respectively. Using pooled migraine summary data with no sample overlap, MR analysis showed per standard deviation increase in circulating vitamin D levels was significantly associated with a decreased migraine risk (OR = 0.916, 95% CI = 0.859–0.977, p = 0.008). Multivariable MR analyses, sensitivity analyses and replication analysis confirmed the association. MR analyses showed similar estimates for migraine with aura and migraine without aura but with wider 95% CIs. Mediation analysis showed the effect of vitamin D on migraine risk via pathway of serum calcium was corresponding to an OR of 1.003 (95% CI = 1.001–1.005) and a proportion mediated of 3.42%. The reverse MR analysis showed migraine might not affect vitamin D levels.ConclusionThis two-sample MR study showed genetically determined increased circulating vitamin D levels are associated with decreased migraine risk. The effect seems consistent across different migraine subtypes. In addition, the role of serum calcium in mediating the association between vitamin D and migraine is negligible. Future large well-designed randomized trials are warranted to assess the effects of vitamin D supplementation for migraine patients, especially in those with vitamin D deficiency.

show abstract

The impact of neurocognitive and psychiatric disorders on the risk of idiopathic normal pressure hydrocephalus: A bidirectional Mendelian randomization study

He,

Wang,

Zuo

et al. 2024

Brain and Behavior

View full text Add to dashboard Cite

BackgroundNeurocognitive and psychiatric disorders have been proved that they can comorbid more often with idiopathic normal pressure hydrocephalus (iNPH) than general population. However, the potential causal association between these disorders and iNPH has not been assessed. Thus, our study aims to investigate the causal relationship between them based on a bidirectional Mendelian randomization (MR) analysis.MethodsRandom effects of the inverse variance weighted (IVW) method were conducted to obtain the causal association among the neurocognitive disorders, psychiatric disorders, and iNPH. Genome‐wide association studies (GWAS) of 12 neurocognitive and psychiatric disorders were downloaded via the OpenGWAS database, GWAS Catalog, and Psychiatric Genomics Consortium, whereas GWAS data of iNPH were obtained from the FinnGen consortium round 9 release, with 767 cases and 375,610 controls of European ancestry. We also conducted the sensitivity analysis in these significant causal inferences using weighted median model, Cochrane's Q test, MR‐Egger regression, MR Pleiotropy Residual Sum and Outlier detect and the leave‐one‐out analysis.ResultsFor most of the neurocognitive and psychiatric disorders, no causal association was established between them and iNPH. We have found that iNPH (odds ratio [OR] = 1.030, 95% confidence interval [CI]: 1.011–1.048, p = .001) is associated with increased risk for schizophrenia, which failed in validation of sensitivity analysis. Notably, genetically predicted Parkinson's disease (PD) is associated with increased risk of iNPH (OR = 1.256, 95% CI: 1.045–1.511, p = .015).ConclusionOur study has revealed the potential causal effect in which PD associated with an increased risk of iNPH. Further study is warranted to investigate the association between PD and iNPH and the potential underlying mechanism.

show abstract

New and sex-specific migraine susceptibility loci identified from a multiethnic genome-wide meta-analysis

Cited by 36 publications

References 96 publications

Migraine and Ischemic Stroke: A Mendelian Randomization Study

Migraine and Ischemic Stroke: A Mendelian Randomization Study

Higher Circulating Vitamin D Levels Are Associated With Decreased Migraine Risk: A Mendelian Randomization Study

The impact of neurocognitive and psychiatric disorders on the risk of idiopathic normal pressure hydrocephalus: A bidirectional Mendelian randomization study

Contact Info

Product

Resources

About