Association analysis of STX1A gene variants in common forms of migraine

TY - JOUR

T1 - Association analysis of STX1A gene variants in common forms of migraine

AU - Tropeano, Maria

AU - Woeber-Bingoel, Cicek

AU - Karwautz, Andreas

AU - Wagner, Gudrun

AU - Vassos, Evangelos

AU - Campos-de-Sousa, Sara

AU - Graggaber, Andrea

AU - Zesch, Heidi E.

AU - Kienbacher, Christian

AU - Natriashvili, Sofia

AU - Kanbur, Incifer

AU - Woeber, Christian

AU - Collier, David A.

PY - 2012/2

Y1 - 2012/2

N2 - 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.

AB - 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.

U2 - 10.1177/0333102411433300

DO - 10.1177/0333102411433300

M3 - Article

VL - 32

SP - 203

EP - 212

JO - Cephalalgia

JF - Cephalalgia

IS - 3

M1 - N/A

ER -