A Brain-Wide Genome-Wide Association Study of Candidate Quantitative Trait Loci Associated with Structural and Functional Phenotypes of Pain Sensitivity

Individual pain sensitivity is influenced by many factors, such as the differentiation of brain regional features and genetic variations. However, its heritability remains largely unclear. The present study conducted a brain-wide genome-wide association study (GWAS) to explore the genetic bases of structural and functional neuroimage phenotypes of pain sensitivity. In total 432 normal participants were firstly divided into high and low pain sensitivity groups according to laser quantitative test threshold and related brain regions gray matter density (GMD) features were identified. Consequently, GWAS was performed on each GMD phenotype using quality-controlled genotypes. Based on the heatmap and hierarchical clustering results from GWAS, the right insula was selected for further refined analysis in terms of sub-regions GMD and resting-state functional connectivity (rs-FC) phenotypes. The results indicate that the right insula GMD in the high sensitivity group is significantly lower than the low sensitivity group. Also, the TT/TC group at locus rs187974 may lead to a lower GMD in the right insula than the CC group. Meanwhile, loci at gene CYP2D6 may lead to a variation of rs-FC between the right insula and left putamen. In conclusion, our study suggests multiple candidate loci associated with pain sensitivity that may influence brain phenotypes.