ArticleThe journal of headache and pain2025
Mapping the brain cell-specific regulatory architecture of migraine: a single-cell causal framework nominating inhibitory-neuronal BTBD16 and astrocytic RIMS1 as therapeutic targets.
Article in The journal of headache and pain, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
2 citing papers in PubMed.
- Buwang Formula Regulates Microglial Metabolic Reprogramming and Modulates the mTOR/HIF-1α Pathway to Reduce Neuroinflammation in Diabetic Mice.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Mapping the Neurovascular Unit Genetic Architecture of Early-Onset Ischemic Stroke: A Single-Cell Causal Framework for Target Discovery and Therapeutic Translation.Cellular and molecular neurobiology · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
Abstract
backgroundMigraine is a common, disabling neurological disorder. Genome-wide association studies have mapped numerous migraine risk loci, but the causal genes and their cell-type context remain unclear. Prior work linked migraine GWAS to bulk brain eQTLs; however, tissue-average signals obscure cell-specific regulation.
methodsWe extended these findings to single-cell resolution. Cis-eQTL instruments from 183 human donors across eight brain cell types were filtered by genome-wide significance, LD pruning, and instrument strength, yielding 1,746 independent eGenes. Two-sample Mendelian randomization (MR) tested effects on migraine risk in FinnGen R12 (discovery) with replication in UK Biobank (GCST90473326). To control for multiple testing, we applied within-cell-type Bonferroni correction and global false discovery rate (FDR) adjustment. Bayesian colocalization was performed in both discovery and replication cohorts to evaluate shared causal variants. We also performed a phenome-wide association screen (PheWAS) and profiled regional brain RNA.
resultsEleven eGenes were significant in FinnGen. Protective associations were observed for BTBD16 in excitatory and inhibitory neurons, RRP15 in excitatory neurons, CCDC146 and GSTM3 in oligodendrocytes, and PDE4B in microglia. Risk-increasing associations were found for GSTM2 (excitatory neurons), RIMS1 and DPH1 (astrocytes), AADAC (microglia), and RBM20 (endothelium). Replication supported signals for inhibitory-neuronal BTBD16 and astrocytic RIMS1. Colocalization analyses indicated shared causal variants at both loci in the discovery cohort (PP.H4 > 0.80). PheWAS showed no genome-wide liabilities for either gene. Regional expression suggested white-matter enrichment for BTBD16 and a cerebellar peak for RIMS1.
conclusionsCell-type-specific MR sharpens migraine mechanisms beyond bulk tissue and prioritizes inhibitory-neuronal BTBD16 (protective) and astrocytic RIMS1 (risk-increasing) for mechanistic validation and therapeutic exploration.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.