Association analysis of STX1A gene variants in common forms of migraine

• Published in: Cephalalgia 2012-02, Vol.32 (3), p.203-212
• Main Authors: Tropeano, Maria, Wöber-Bingöl, Çiçek, Karwautz, Andreas, Wagner, Gudrun, Vassos, Evangelos, Campos-de-Sousa, Sara, Graggaber, Andrea, Zesch, Heidi E, Kienbacher, Christian, Natriashvili, Sofia, Kanbur, Incifer, Wöber, Christian, Collier, David A
• Format: Article
• Language: English
• Subjects: Adolescent; Case-Control Studies; Child; Female; Genetic Predisposition to Disease - genetics; Genetic Variation; Genome-Wide Association Study; Genotype; Humans; Male; Migraine Disorders - genetics; Pedigree; Syntaxin 1 - genetics; Young Adult
• ISSN: 0333-1024; 1468-2982
• DOI: 10.1177/0333102411433300

Objectives: To examine the association of genetic variants in the syntaxin 1A gene (STX1A) with common forms of migraine, and perform a combined analysis of the data from the current study and previously published reports. Methods: We investigated the parent-to-offspring transmission of rs6951030, rs4363087 and rs2293489 in 191 family trios, each with a proband with childhood-onset migraine, and performed a case-control analysis between the probands and 223 unrelated controls. In addition, we performed a combined data analysis with an overall sample of 567 migraine patients and 720 unrelated controls and performed a migraine-specific gene-network analysis. Results: The transmission disequilibrium test revealed significant transmission distortion of rs4363087 in migraine overall (OR = 1.56, p = 0.006; p = 0.01 after correction for multiple testing) and migraine without aura (OR = 1.58, p = 0.01; corrected p = 0.04). Two-marker haplotype analysis revealed transmission distortion of A-G (rs6951030-rs4363087; OR = 1.47, p = 0.01) and A-C (rs4363087-rs2293489; OR = 0.66, p = 0.01). Combined analysis showed significant association of rs941298 with migraine overall (OR = 1.28, p = 0.004) and migraine without aura (OR = 1.3, p = 0.008). Network analysis identified 24 genes relating STX1A to other migraine candidate genes, including KCNK18 (TRESK channel) involved in the cytoplasmatic calcium signalling together with syntaxin 1A. Conclusion: Our results provide support for the hypothesis that STX1A represents a susceptibility gene for migraine.