Multivariate genome-wide analysis of stress-related quantitative phenotypes

Schijven, Dick; Geuze, Elbert; Vinkers, Christiaan H.; Pulit, Sara L.; Schür, Remmelt R.; Malgaz, Marie; Bekema, Erwin; Medic, Jelena; van der Kust, Kendrick E.; Veldink, Jan H.; Boks, Marco P.; Vermetten, Eric; Luykx, Jurjen J.

doi:10.1016/j.euroneuro.2019.09.012

アイテム詳細

登録内容を編集ファイル形式で保存

一時保存へ追加

タグ情報を表示リリース履歴を表示詳細要約

公開

学術論文

Multivariate genome-wide analysis of stress-related quantitative phenotypes

MPS-Authors

There are no MPG-Authors in the publication available

External Resource

There are no locators available

Fulltext (restricted access)

There are currently no full texts shared for your IP range.

フルテキスト (公開)

公開されているフルテキストはありません

付随資料 (公開)

There is no public supplementary material available

引用

Schijven, D., Geuze, E., Vinkers, C. H., Pulit, S. L., Schür, R. R., Malgaz, M., Bekema, E., Medic, J., van der Kust, K. E., Veldink, J. H., Boks, M. P., Vermetten, E., & Luykx, J. J. (2019). Multivariate genome-wide analysis of stress-related quantitative phenotypes. European Neuropsychopharmacology, 29(12), 1354-1364. doi:10.1016/j.euroneuro.2019.09.012.

引用: https://hdl.handle.net/21.11116/0000-0004-D5F1-B

要旨

Exposure to traumatic stress increases the odds of developing a broad range of psychiatric conditions. Genetic studies targeting multiple stress-related quantitative phenotypes may shed light on mechanisms underlying vulnerability to psychopathology in the aftermath of stressful events. We applied a multivariate genome-wide association study (GWAS) to a unique military cohort (N = 583) in which we measured biochemical and behavioral phenotypes. The availability of pre- and post-deployment measurements allowed to capture changes in these phenotypes in response to stress. For genome-wide significant loci, we performed functional annotation, phenome-wide analysis and quasi-replication in PTSD case-control GWASs. We discovered one genetic variant reaching genome-wide significant association, surviving permutation and sensitivity analyses (rs10100651, p = 9.9 × 10−9). Functional annotation prioritized the genes INTS8 and TP53INP1. A phenome-wide scan revealed a significant association of these same genes with sleeping problems, hypertension and subjective well-being. Finally, a targeted lookup revealed nominally significant association of rs10100651 in a PTSD case-control GWAS in the UK Biobank (p = 0.02). We provide comprehensive evidence from multiple resources hinting at a role of the highlighted genetic variant in the human stress response, marking the power of multivariate genome-wide analysis of quantitative measures in stress research. Future genetic and functional studies can target this locus to further assess its effects on stress mediation and its possible role in psychopathology or resilience.