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Genome-wide association analysis of treatment response to onabotulinumtoxinA in Han Chinese patients with chronic migraine: a pilot study

Yu-Chin An, Chih‐Sung Liang, Chia‐Kuang Tsai, Chia‐Lin Tsai, Yu-Kai Lin, Wen-I Liao, Po-Kuan Yeh, Guan-Yu Lin et al.

BMC Neurology, 2026

1 citation

Abstract

BACKGROUND/OBJECTIVES: OnabotulinumtoxinA (BoNT-A) use is an established preventive treatment for chronic migraine (CM); however, individual response rates vary. Although genetic factors may contribute to this variability, the underlying genetic determinants remain largely undefined, especially in Asian populations. Therefore, we aimed to identify genetic variants associated with the response to BoNT-A treatment in Han Chinese patients with CM. METHODS: We conducted a genome-wide quantitative trait locus (QTL) analysis using the Taiwan Precision Medicine (TPM) array in Han Chinese patients with CM receiving BoNT-A treatment according to the PREEMPT protocol. Treatment efficacy was assessed by calculating the improvement in monthly headache days after 24 weeks compared with baseline. Genotype–phenotype associations were assessed using a linear regression model adjusted for relevant clinical covariates. Functional annotation, Gene Ontology (GO) annotation, and linkage disequilibrium (LD) mapping were performed to interpret the biological importance of significant variants. RESULTS: We identified four intronic single nucleotide polymorphisms (SNPs) that showed genome-wide significance: rs11147666 in TRPC4, rs3924647 in LINC02197, rs56381512 in GTF2H2, and rs13126813 in SPOCK3. rs11147666 in TRPC4 showed the strongest association with treatment response. Patients with heterozygous variants showed lower improvement rates than those with common homozygotes. The implicated genes…

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