Recent research had shed light on the genetic basis of the link between migraine and certain blood sugar-related traits – like fasting insulin and glycated haemoglobin – with the potential relationship paving the way for developing new prevention and treatment options for millions of sufferers worldwide.
Previously, it was unclear how these conditions were genetically linked, so to investigate, researchers analysed large-scale genetic data from hundreds of thousands of human genomes, with and without migraine or headache history, in European populations.
They looked for genetic similarities between migraine, headache, and nine blood sugar-related traits, and also identified regions of the genome linked to both types of conditions.
They also suggested a potential causal relationship between increased fasting pro-insulin levels and decreased risk of headaches.
The team conducted a meta-analysis with blood sugar-related traits that they say identified six new genetic markers associated with migraine and headache, finding that certain genes were associated with these conditions, reports Medical News Today.
These findings, they wrote in Human Genetics, provide insights into the biological mechanisms underlying the comorbidity of these conditions.
Using a statistical technique called Mendelian randomisation, they examined the causal relationship between mechanisms and conditions.
While they reported there was some evidence to suggest increased fasting pro-insulin levels might decrease the risk of headaches, the evidence for a causal link between migraine and other blood sugar-related traits was less clear.
However, overall, these findings suggest that migraine, headache, and blood sugar-related traits may have a common genetic basis and provide insights into how they contribute to their co-occurrence.
"Our study revealed a significant overlap between the genetic risk factors (e.g. genes and genetic variants) for migraine and blood sugar regulation, suggesting that these conditions have a common genetic basis,” said Md Rafiqul Islam, a study author and student at the School of Biomedical Sciences at the Centre for Genomics and Personalised Health at Queensland University of Technology, Australia.
“Additionally, we identified several genetic regions associated with an increased risk for both conditions, indicating they share similar biological pathways and mechanisms.”
The study found that shared genetic risk factors for these diseases are significantly enriched in certain cellular pathways, including epigenetic mechanisms, autoimmune pathways, and cellular signalling, providing important clues about the underlying mechanisms of these conditions which might help researchers develop new treatments.
Sarah-Nicole Bostan, director of Behaviour Change Strategy at Signos, a US company behind an AI-driven app to deliver real-time glucose monitoring and who was not involved in this research, said: “Migraine and headaches are two of the most common types of pain-related issues most likely to be reported to non-physician healthcare providers.
“They often lead to unnecessary medical visits and costs.”
Both are unusual in that they are disorders of exclusion, meaning diagnoses are arrived at by ruling out serious pathology, which is an inverse process compared with other health conditions. This often leaves patients frustrated and confused about what actionable steps they can take to manage their pain and wondering what might be the root cause.
Bostan said that in the field of applied psychophysiology and biofeedback, headaches are usually caused by tight muscles, while migraine is often caused by problems with blood flow.
Knowing the difference between these two types of pain can help people treat their symptoms by learning relaxation techniques like heart rate variability biofeedback, muscle tension biofeedback, making changes to their diet, and taking time to rest or exercise during a migraine.
“This research provides a glimpse of how metabolic and cardiorespiratory factors may be working in tandem even at the genetic level, and how there may be shared genetic etiology of headaches and migraines,” she noted.
Potential implications
Islam said researchers “found shared genes, genetic variants, and pathways associated with an increased risk of migraine and blood sugar imbalance”.
“With this information, researchers can make new screening tests to find people at high risk of developing migraine and blood sugar-related diseases (e.g. diabetes) even before they show symptoms, leading to earlier diagnosis and treatment, and improving patient outcomes.”
Bostan said that “although this research found inconsistent evidence regarding the impact of glycaemic traits on headaches/migraine and the team noted that their findings were only ‘nominally significant’, it opens a door to further studying the specific glycaemic traits that may be ripe for changing to influence pain pathology”.
Many people have noted that they don’t realise their blood sugar may be dipping quickly before experiencing migraine or headache pain, and once they stabilise their blood sugar through eating a nutritionally balanced meal, they may be able to relieve some of this pain if they intervene early enough.
“The takeaway here is that our metabolic stability can influence pain, and therefore, use of metabolically-targeted interventions may be even more important than previously known,” said Bostan.
Study details
Cross-trait analyses identify shared genetics between migraine, headache, and glycemic traits, and a causal relationship with fasting proinsulin
Rafiqul Islam, The International Headache Genetics Consortium (IHGC) & Dale Nyholt.
Published in Human Genetics on 20 February 2023
Abstract
The co-occurrence of migraine and glycaemic traits has long been reported in observational epidemiological studies, but it has remained unknown how they are linked genetically. We used large-scale GWAS summary statistics on migraine, headache, and nine glycaemic traits in European populations to perform cross-trait analyses to estimate genetic correlation, identify shared genomic regions, loci, genes, and pathways, and test for causal relationships. Out of the nine glycaemic traits, significant genetic correlation was observed for fasting insulin (FI) and glycated haemoglobin (HbA1c) with both migraine and headache, while 2-h glucose was genetically correlated only with migraine. Among 1703 linkage disequilibrium (LD) independent regions of the genome, we found pleiotropic regions between migraine and FI, fasting glucose (FG), and HbA1c, and pleiotropic regions between headache and glucose, FI, HbA1c, and fasting pro-insulin. Cross-trait GWAS meta-analysis with glycaemic traits, identified six novel genome-wide significant lead SNPs with migraine, and six novel lead SNPs with headache (Pmeta < 5.0 × 10–8 and Psingle-trait < 1 × 10–4), all of which were LD-independent. Genes with a nominal gene-based association (Pgene ≤ 0.05) were significantly enriched (overlapping) across the migraine, headache, and glycaemic traits. Mendelian randomisation analyses produced intriguing, but inconsistent, evidence for a causal relationship between migraine and headache with multiple glycaemic traits; and consistent evidence suggesting increased fasting pro-insulin levels may causally decrease the risk of headache.
Our findings indicate that migraine, headache, and glycaemic traits share a common genetic etiology and provide genetic insights into the molecular mechanisms contributing to their comorbid relationship.
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Migraine in children linked to anxiety, depression – Canadian meta-analysis
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Cinnamon may improve blood sugar control in pre-diabetics — Clinical trial
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