Trauma and posttraumatic stress interact with sex-specific risk loci for suicidality and converge on brain extracellular matrix biology and synaptic plasticity
Frank R Wendt,
Gita A Pathak,
Daniel F Levey,
Yaira Z. Nunez,
Flavio De Angelis,
Daniel S. Tylee,
John H Krystal,
Murray B Stein,
Henry R. Kranzler,
Posted 21 May 2020
medRxiv DOI: 10.1101/2020.05.18.20105734
Posted 21 May 2020
We performed a multivariate gene-by-environment genome-wide interaction study (GEWIS) of suicidality in 123,633 individuals using a covariance matrix based on 26 environments related to traumatic experiences, posttraumatic stress, social support, and socioeconomic status. We discovered sex-specific risk loci exhibiting interaction effects driven by PTSD, including the male-specific rs2367967 (CWC22), which replicated in an independent cohort. Sex-specific cell-type transcriptome enrichment, gene-based analyses, and locus annotation point to extracellular matrix biology and synaptic plasticity as biological mediators of the effects of lifetime traumatic experiences on genetic risk for suicidality.
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