A UK Biobank study of over 220,000 people studied headache as a single, broadly self-reported experience — not restricted to a clinical migraine diagnosis — and found 28 associated loci.
Headache is the most common neurological symptom people experience, and it is not one thing: pain from tension, sinus pressure, dehydration, or a migraine attack can all be reported simply as "a headache." This page covers genetic variants associated with headache as a broad, self-reported experience, deliberately distinct from this site's separate Migraine page, which covers a specific, clinically diagnosed condition with its own attack pattern and treatment.
Meng et al. 2018 studied headache as a single entity in 223,773 UK Biobank participants — 74,461 people who reported headache and 149,312 who did not — based on how participants answered one broad survey question, not a clinical diagnosis. The study found 3,343 significant genetic variants across 28 loci. The single strongest signal was rs11172113 in LRP1 — not itself one of this page's own variants. Of the 28 loci, 14 had already been linked specifically to migraine in earlier research, and 14 were newly identified for headache broadly — the strongest of the new loci sat near LINC02210-CRHR1. The study also found significant genetic correlations between headache and several psychological traits, and tissue-expression analysis pointed to multiple brain regions.
This page's 9 variants come from that broad, self-reported headache phenotype specifically — a deliberately different question from the clinical migraine diagnosis this site's separate Migraine page covers, even though the two overlap substantially at the genetic level.
2026-08-04 · Genome-wide association susceptibility loci for cluster headache support a role for inflammation in the pathophysiology. Journal of Headache and Pain. 2026. DOI:10.1186/s10194-026-02485-x
Two functional gene variants strengthen the case that cluster headache is an inflammatory disease
Cluster headache is a distinct, severe headache disorder from migraine, and this study followed up on genetic loci from earlier GWAS to determine which are functionally real rather than statistical noise. Using a case-control study (671 individuals) plus meta-analysis, methylation analysis and gene expression studies in cluster headache patients versus controls, the study validated functional variants at two genes specifically: FHL5 and MERTK. Both showed evidence of altered methylation and gene expression consistent with a functional -- not just statistical -- role, supporting a role for inflammation in cluster headache's pathophysiology alongside its known links to circadian regulation. This site's headache page carries 9 variants, distinct from its migraine page's 117 variants (cluster headache and migraine are genetically and clinically separate conditions); neither FHL5 nor MERTK are currently among them.
This page is not about migraine specifically, and none of its variants diagnoses any headache disorder. Headache has many distinct causes — from tension and dehydration to migraine and, rarely, more serious underlying conditions — and this page cannot distinguish between them.
For a specific, clinically diagnosed headache condition with its own diagnostic criteria and treatments, see this site's separate Migraine page. Persistent, severe, or unusual headache always warrants clinical evaluation regardless of anything on this page.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Headache comes down to these specific, well-studied positions — not a diagnosis.
The studies behind these variants recruited participants from different ancestries — a result found in one population doesn't always transfer to another. Based on 9 of 9 linked studies with a resolved discovery ancestry.
Databases, guidelines and references
This page covers headache as a broad, self-reported experience from one UK Biobank survey question, not restricted to any specific diagnosis. This site's separate Migraine page covers a specific, clinically diagnosed condition with its own diagnostic criteria.
In 223,773 UK Biobank participants, it found 28 loci associated with broadly-defined headache. 14 of those loci had already been linked to migraine specifically, and 14 were newly identified for headache more broadly.
No. Headache has many distinct causes, and this broad, self-reported research trait cannot distinguish between them. Persistent or unusual headache warrants clinical evaluation.
No individual variant does. These are population-level statistical associations from a survey-based study, not a predictive or diagnostic test.
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