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Multilocus analysis of hormonal, neurotransmitter, inflammatory pathways and genome‐wide associated variants in migraine susceptibility
Author(s) -
Ghosh J.,
Pradhan S.,
Mittal B.
Publication year - 2014
Publication title -
european journal of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 124
eISSN - 1468-1331
pISSN - 1351-5101
DOI - 10.1111/ene.12427
Subject(s) - multifactor dimensionality reduction , migraine , medicine , genome wide association study , genetics , genetic association , gene , bioinformatics , biology , endocrinology , single nucleotide polymorphism , genotype
Background and purpose Migraine pathophysiology involves a complex interplay of processes wherein the hormonal, neurotransmitter and inflammatory pathways interact to influence the migraine phenotype. However, all studies pertaining to the role of genetic variants in migraine have been restricted to a specific pathway and none of the studies has looked into inter‐pathway genetic analysis. Our aim was to combine all the genetic variants from our previously reported studies to conduct higher order gene–gene interaction analysis using different multi‐analytical approaches. Methods The study group included 324 migraine patients and 134 healthy controls. The study included 20 polymorphisms from hormonal, neurotransmitter, inflammatory and genome‐wide associated variants from our published reports. Univariate and multivariate analyses were carried out by logistic regression. Classification and regression tree ( CART ) analysis was performed to build a decision tree via recursive partitioning. The high order genetic interactions associated with migraine risk were analyzed using multifactor dimensionality reduction ( MDR ). Results Univariate analysis revealed significant associations of polymorphisms in CYP 19 A 1 , ESR 1 , TNFA and PRDM 16 genes with migraine susceptibility. Multiple regression analysis found significant results for four markers in CYP 19 A 1 , TNFA , ESR 1 and LRP 1 genes. In CART , the most prominent splitting variable was CYP 19 A 1 polymorphism followed by TNFA , ESR 1 and PRDM 16 markers. The MDR analysis identified markers of CYP 19 A 1 , CYP 19 A 1 ‐ TNFA , CYP 19A1 ‐ ESR 1 ‐ TNFA and CYP 19 A 1 ‐ ESR 1 ‐ TRPM 8 ‐ PRDM 16 as best models for one, two, three and four factors, respectively. Conclusions The present study suggests interactions amongst hormonal, inflammatory and genome‐wide associated variants but not with neurotransmitter pathway variants in migraine susceptibility.