Scholarlink

Background/Objectives <p>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.</p> Methods <p>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.</p> Results <p>We identified four intronic single nucleotide polymorphisms (SNPs) that showed genome-wide significance: rs11147666 in <i>TRPC4</i>, rs3924647 in <i>LINC02197</i>, rs56381512 in <i>GTF2H2</i>, and rs13126813 in <i>SPOCK3</i>. rs11147666 in <i>TRPC4</i> showed the strongest association with treatment response. Patients with heterozygous variants showed lower improvement rates than those with common homozygotes. The implicated genes function in calcium ion transport, transcriptional regulation, and extracellular matrix interactions. Given the modest sample size and low minor allele frequencies, these findings should be interpreted as exploratory signals.</p> Conclusion <p>This pilot genome-wide association study identified genetic variants linked to variability in BoNT-A response among Han Chinese patients with chronic migraine, highlighting potential candidate loci for future validation. Given the limited sample size and absence of an independent replication cohort, the reported loci should be interpreted as exploratory and hypothesis-generating findings.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月15日

查看全文
  • Yu-Chin An,
  • Chih-Sung Liang,
  • Chia-Kuang Tsai,
  • Chia-Lin Tsai,
  • Yu-Kai Lin,
  • Wen-I Liao,
  • Po-Kuan Yeh,
  • Guan-Yu Lin,
  • Cheng-Hao Hsieh,
  • Kuo-Sheng Hung,
  • Fu-Chi Yang

摘要

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 function in calcium ion transport, transcriptional regulation, and extracellular matrix interactions. Given the modest sample size and low minor allele frequencies, these findings should be interpreted as exploratory signals.

Conclusion

This pilot genome-wide association study identified genetic variants linked to variability in BoNT-A response among Han Chinese patients with chronic migraine, highlighting potential candidate loci for future validation. Given the limited sample size and absence of an independent replication cohort, the reported loci should be interpreted as exploratory and hypothesis-generating findings.