Increasing sample diversity in psychiatric genetics – Introducing a new cohort of patients with schizophrenia and controls from Vietnam – Results from a pilot study

Abstract

Objectives

Genome-Wide Association Studies (GWAS) of Schizophrenia (SCZ) have provided new biological insights; however, most cohorts are of European ancestry. As a result, derived polygenic risk scores (PRS) show decreased predictive power when applied to populations of different ancestries. We aimed to assess the feasibility of a large-scale data collection in Hanoi, Vietnam, contribute to international efforts to diversify ancestry in SCZ genetic research and examine the transferability of SCZ-PRS to individuals of Vietnamese Kinh ancestry.

Methods

In a pilot study, 368 individuals (including 190 SCZ cases) were recruited at the Hanoi Medical University's associated psychiatric hospitals and outpatient facilities. Data collection included sociodemographic data, baseline clinical data, clinical interviews assessing symptom severity and genome-wide SNP genotyping. SCZ-PRS were generated using different training data sets: (i) European, (ii) East-Asian and (iii) trans-ancestry GWAS summary statistics from the latest SCZ GWAS meta-analysis.

Results

SCZ-PRS significantly predicted case status in Vietnamese individuals using mixed-ancestry (R² liability = 4.9%, p = 6.83 × 10⁻⁸), East-Asian (R² liability = 4.5%, p = 2.73 × 10⁻⁷) and European (R² liability = 3.8%, p = 1.79 × 10⁻⁶) discovery samples.

Discussion

Our results corroborate previous findings of reduced PRS predictive power across populations, highlighting the importance of ancestral diversity in GWA studies.

Keywords:

• Schizophrenia
• GWAS
• Vietnam
• East-Asia
• polygenic prediction

Acknowledgements

We thank the Schizophrenia Working Group of the Psychiatric Genomics Consortium for granting permission to use European, East-Asian and trans-ancestry GWAS summary statistics (wave 3) for this study. The Stanley Center for Psychiatric Research financially supported the collection of this sample. The statistical analysis was carried out on the Dutch LISA computer cluster powered by SURFsara. We further thank the participants and additional staff of Hanoi Psychiatric Hospital, Hanoi Medical University, and the National Institute of Mental Health, Vietnam, for taking part in this study.

Statement of interest

None of the authors involved in this manuscript report conflicts of interest.

Additional information

Funding

This work was supported by the Stanley Center for Psychiatric Research, Broad Institute.