Polygenic prediction and GWAS of depression, PTSD, and suicidal ideation/self-harm in a Peruvian cohort

Abstract

Genome-wide approaches including polygenic risk scores (PRSs) are now widely used in medical research; however, few studies have been conducted in low- and middle-income countries (LMICs), especially in South America. This study was designed to test the transferability of psychiatric PRSs to individuals with different ancestral and cultural backgrounds and to provide genome-wide association study (GWAS) results for psychiatric outcomes in this sample. The PrOMIS cohort (N = 3308) was recruited from prenatal care clinics at the Instituto Nacional Materno Perinatal (INMP) in Lima, Peru. Three major psychiatric outcomes (depression, PTSD, and suicidal ideation and/or self-harm) were scored by interviewers using valid Spanish questionnaires. Illumina Multi-Ethnic Global chip was used for genotyping. Standard procedures for PRSs and GWAS were used along with extra steps to rule out confounding due to ancestry. Depression PRSs significantly predicted depression, PTSD, and suicidal ideation/self-harm and explained up to 0.6% of phenotypic variation (minimum p = 3.9 × 10−6). The associations were robust to sensitivity analyses using more homogeneous subgroups of participants and alternative choices of principal components. Successful polygenic prediction of three psychiatric phenotypes in this Peruvian cohort suggests that genetic influences on depression, PTSD, and suicidal ideation/self-harm are at least partially shared across global populations. These PRS and GWAS results from this large Peruvian cohort advance genetic research (and the potential for improved treatments) for diverse global populations.

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Fig. 1: Principal components plots of PrOMIS and 1000Genomes participants.
Fig. 2: Polygenic prediction results in the PrOMIS cohort for three phenotypes (depression severity score, PTSD severity score, and suicidal ideation/self-harm) using two psychiatric polygenic risk scores, controlling for covariates.
Fig. 3: Magnitude of effects of polygenic scores and covariates on psychiatric outcome variables.

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Acknowledgements

The authors are indebted to the participants of the PrOMIS study for their cooperation. They are also grateful to the dedicated staff members of Asociacion Civil Proyectos en Salud (PROESA), Peru and Instituto Especializado Maternao Perinatal, Peru, for their expert technical assistance with this research. Some of the computing for this project was performed on the Sherlock cluster. We would like to thank Stanford University and the Stanford Research Computing Center for providing computational resources and support that contributed to these research results.

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LED, BG, HS conceived of the investigation and developed the analysis plan. MBR, SS, BG recruited and communicated with participants, and collected and cleaned the clinical data. HS conducted the analyses. HS and LED did the literature review for the paper. HS, LED, BG, and HH drafted the manuscript, and all authors contributed and edited the final manuscript.

Corresponding authors

Correspondence to Bizu Gelaye or Laramie E. Duncan.

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Shen, H., Gelaye, B., Huang, H. et al. Polygenic prediction and GWAS of depression, PTSD, and suicidal ideation/self-harm in a Peruvian cohort. Neuropsychopharmacol. 45, 1595–1602 (2020). https://doi.org/10.1038/s41386-020-0603-5

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