The heritability of BP is estimated at 80% and adoption, twin and family studies have consistently identified a significant genetic contribution;3, 4 many genes5 and genetic mechanisms6 have been implicated in BP, consistent with multiple disease loci, each contributing modest effects.7,8 Genome-wide association studies have identified a few replicated loci including polymorphisms in CACNA1C, the alpha subunit of the L-type voltage-gated calcium channel, the strongest and most replicated risk.5,9, 10, 11, 12, 13 Additional replicated polymorphisms have been identified in ANK3, which regulates assembly of voltage-gated sodium channels at the node of Ranvier,14,15 and SYNE1, which has a critical role in synaptic clustering.16 Overall, available data suggest that alterations in membrane organization and/or ion channelopathies may contribute to BP; in fact, dysregulation of Ca2+ signaling is one of the most reproducible observations in BP.17
