Genome-wide association study identifies novel susceptibility loci for migraine in Han Chinese resided in Taiwan

Shih Pin Chen, Jong Ling Fuh, Ming Yi Chung, Ying Chao Lin, Yi Chu Liao, Yen Feng Wang, Chia Lin Hsu, Ueng Cheng Yang, Ming Wei Lin, Jen Jie Chiou, Po Jen Wang, Ping Kun Chen, Pi Chuan Fan, Jer Yuan Wu, Yuan Tsong Chen, Lung Sen Kao, Cathy Shen-Jang Fann, Shuu Jiun Wang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Background: Susceptibility genes for migraine, despite it being a highly prevalent and disabling neurological disorder, have not been analyzed in Asians by genome-wide association study (GWAS). Methods: We conducted a two-stage case-control GWAS to identify susceptibility genes for migraine without aura in Han Chinese residing in Taiwan. In the discovery stage, we genotyped 1005 clinic-based Taiwanese migraine patients and 1053 population-based sex-matched controls using Axiom Genome-Wide CHB Array. In the replication stage, we genotyped 27 single-nucleotide polymorphisms with p < 10−4 in 1120 clinic-based migraine patients and 604 sex-matched normal controls by using Sequenom. Variants at LRP1, TRPM8, and PRDM, which have been replicated in Caucasians, were also genotyped. Results: We identified a novel susceptibility locus (rs655484 in DLG2) that reached GWAS significance level for migraine risk in Han Chinese (p = 1.45 × 10−12, odds ratio [OR] = 2.42), and also another locus (rs3781545in GFRA1) with suggestive significance (p = 1.27 × 10−7, OR = 1.38). In addition, we observed positive association signals with a similar trend to the associations identified in Caucasian GWASs for rs10166942 in TRPM8 (OR = 1.33, 95% confidence interval [CI] = 1.14–1.54, Ppermutation = 9.99 × 10−5; risk allele: T) and rs1172113 in LRP1 (OR = 1.23, 95% CI = 1.04–1.45, Ppermutation = 2.9 × 10−2; risk allele: T). Conclusion: The present study is the first migraine GWAS conducted in Han-Chinese and Asians. The newly identified susceptibility genes have potential implications in migraine pathogenesis. DLG2 is involved in glutamatergic neurotransmission, and GFRA1 encodes GDNF receptors that are abundant in CGRP-containing trigeminal neurons. Furthermore, positive association signals for TRPM8 and LRP1 suggest the possibility for common genetic contributions across ethnicities.

Original languageEnglish
Pages (from-to)466-475
Number of pages10
JournalCephalalgia
Volume38
Issue number3
DOIs
StatePublished - 1 Mar 2018

Keywords

  • Asian
  • DLG2
  • genome-wide association study
  • GFRA1
  • Han Chinese
  • Migraine
  • Taiwan

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