rs10915437 (LINC02780): Migraine Susceptibility

Key takeaways

• This variant on chromosome 1p36, in the LINC02780 - EEF1DP6 region, is associated with migraine susceptibility across a meta-analysis of 29 studies including more than 23,000 people with migraine.
• The association reached genome-wide significance only in subgroup analyses, not in the primary all-sample analysis, which is an important limitation on the strength of this evidence.
• The variant sits about 500 kb from AJAP1, a brain-expressed gene linked to tumor invasion, and about 300 kb from the CEP104, TP73, and DFFB gene cluster.
• GTEx expression data shows the variant's alternate allele is linked to increased CEP104 expression in spleen tissue.

What the research says A meta-analysis across 29 genome-wide association studies, including 23,285 individuals with migraine and 95,425 population-matched controls, identified rs10915437 on chromosome 1p36 (the LINC02780 - EEF1DP6 region, referred to in that work as the near-AJAP1 locus) as one of five newly discovered loci associated with migraine susceptibility, reaching the conventional genome-wide significance threshold of P < 5 x 10^-8. The variant lies approximately 500 kb toward the tip of chromosome 1 from AJAP1, a gene expressed in brain tissue associated with tumor invasion and regulation of metalloproteinases (enzymes that break down proteins in the spaces around cells), and approximately 300 kb from a cluster containing CEP104, TP73, and DFFB. This locus was among four of the twelve genome-wide significant loci that emerged exclusively from subgroup analyses rather than from the primary analysis pooling all participants together.

Reported associations

• Migraine susceptibility: rs10915437 at the 1p36 locus reached genome-wide significance (P < 5 x 10^-8) in subgroup analyses of a 29-study meta-analysis (23,285 cases and 95,425 controls). The signal was not significant in the primary all-sample analysis, which is an important limitation on confidence in this association.

Evidence quality The migraine association comes from a large multi-cohort meta-analysis with more than 118,000 total participants across 29 studies, providing substantial overall statistical power. However, genome-wide significance at this specific locus was reached only in subgroup analyses - not in the primary all-participant meta-analysis. Subgroup analyses carry a higher risk of false-positive results because multiple comparisons are performed across different participant groups. No independent replication of this specific variant is described in the available data. Overall, the evidence for this locus as a migraine susceptibility site should be considered preliminary.

Tissue-specific expression effects

• CEP104: The alternate allele is associated with increased expression of CEP104 (centrosomal protein 104, involved in building cellular projections called cilia) in spleen tissue, based on GTEx v11 data from 953 donors GTEx Portal. This gene sits approximately 300 kb from the variant within the same chromosomal neighborhood.

Lifestyle considerations No lifestyle considerations on file for this variant.