![]() ![]() Suicide is preventable but its complex etiology requires further study. Suicide is the 10th leading cause of death in the U.S and accounts for almost 800,000 deaths per year globally. ![]() Our findings indicate that variants in NRXN1 and related synaptic genes warrant further study as risk factors for suicide death. Although the formation of hemi-synapses was not altered with the P469S variant relative to wild-type, both variants increased binding to the postsynaptic binding partner, leucine-rich repeat transmembrane neuronal 2 (LRRTM2) in vitro. We tested the impact of these variants on binding interactions with known partners and assessed functionality in a hemi-synapse formation assay. Here we present new evidence for two non-synonymous variants ( rs78540316 P469S and rs199784139 H885Y) associated with increased familial risk of suicide death. Previously, we reported genome-wide evidence that neurexin 1 (NRXN1), a key synapse organizing molecule, is associated with familial suicide risk. ![]() Although the genetic component of suicide is well established, the scope of gene networks and biological mechanisms underlying suicide has yet to be defined. Suicide is a significant public health concern with complex etiology.
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