2024-02-05

075_ Collaboration of PsyCourse with the International Suicide Genetics Consortium, which is now the PGC Suicide Working Group (Amendment to 027)

Research Question and Aims

A very large proportion of people who attempt suicide have a psychiatric diagnosis. Population-based and family studies have shown a substantial heritability of suicide behavior, with estimates from 17 to 55% (Voracek et al., 2007; Sokolowski et al., 2014). Moreover, recent a GWAS studies on suicide attempt and death by suicide has started to shed light on the genetic underpinnings of suicidal behavior in samples with and without psychiatric diagnoses (Docherty et al., 2020; Docherty et al., 2023; Kimbrel et al., 2022; Mullins et al. 2019, Mullins et al., 2022).
Since the previous version of this proposal had been approved, the International Suicide Genetics Consortium has become the PGC Suicide Working Group. Here we propose to contribute to the upcoming GWAS on suicidal attempt (SA) and suicidal ideations (SI) from the PGC Suicide Working Group. We will leverage the fine-grained information available in PsyCourse regarding suicidiology. Briefly, GWAS analyses based on PsyCourse suicide variables will be run locally at the LRZ servers and only summary statistics will be shared with the PGC Suicide Working Group in order to perform a meta-analysis. One investigator will also participate in such meta-analyses as analyst.

Analytic Plan

Main research question: Which common genetic variants contribute to the risk of suicide attempt/completion and suicidal ideation? Participants: data from all samples of patients and healthy controls in PsyCourse who have genotype/suicide phenotype data on SI and SA available will be included in this study.

Statistical analysis: local analyses will involve a genome-wide approach (GWAS) based on imputed variants that will be carried out using PLINK1.90. Population stratification will be corrected for using ancestry principal components. Likewise, center of recruitment will be used as covariate. Age and sex as well as psychiatric diagnosis are not mandatory according to the guidelines of the PGC Suicide Working Group.

Several models will be used:
Model 1: participants with a history of suicide attempt (cases suicide attempt) vs. participants without a history of suicide attempt (controls) Model 2: participants with a history of suicidal ideations (cases suicidal ideation) vs. participants without a history of suicidal ideations (controls)

The resulting summary statistics will be shared with the International Suicide Genetics Consortium.

Resources needed

Phenotype:
v1_sex
v1_age
v1_age_1st_inpat_trm
v1_scid_dsm_dx_cat
v1_scid_evr_suic_ide
v1_suic_attmpt
v2_suic_ide_snc_lst_vst
v2_suic_attmpt_snc_lst_vst
v3_suic_ide_snc_lst_vst
v3_suic_attmpt_snc_lst_vst
v4_suic_ide_snc_lst_vst
v4_suic_attmpt_snc_lst_vst
gsa_id

Genotype:
Raw genotypes pre-imputation to calculate PCAs
Imputed genotypes