A GABBR2 gene variant modifies pathophysiology in Huntington’s disease

摘要: Abstract Striatal degeneration in Huntington’s disease (HD) causes changes cortico-subcortical pathways. Transcranial magnetic stimulation (TMS) is a valuable tool for assessing pathophysiology within these pathways, yet has had limited application HD. As pathways are largely mediated by GABA and dopamine receptor genes, understanding how genes modulate neurophysiology HD may provide new insights into underlying pathology maps onto clinical phenotype. Twenty-nine participants with underwent motor cortex stimulation, while corticospinal excitability, cortical inhibition intracortical facilitation were indexed via peripheral electromyography. Single-nucleotide polymorphism mapping was performed across six that known to ( GABRA2 , GABBR1 GABBR2 DRD1 DRD2 DRD4 ). Genetic associations TMS measures age at onset investigated. Our hierarchical multiple regression analysis, controlling CAG age, revealed variant, predicted be disease-causative, significantly associated excitability corrected levels. A subsequent uncorrected exploratory analysis between variants of HD, as well onset. findings support the notion uncovering genetic pathophysiological an important way forward terms generating meaningful biomarkers diagnostic prognostic sensitivity, identifying novel human-validated targets future trials.