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

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.

Cytotoxicity evaluation of multipurpose contact lens solutions using an in vitro test battery.

PURPOSE: Many in vitro alternatives to eye irritation testing are not mechanism-specific and do not employ ocular cell lines. We have developed an effective and reliable test battery that reveals toxicity mechanisms of contact lens solutions on cell metabolism and proliferation. METHODS: Cytotoxicity endpoints were quantified using bovine corneal epithelial cultures in 96-well microplates. A kenacid blue assay provided information on total cell protein, while lactate production and alamarBlue assays served as indicators of aerobic/anaerobic metabolism and redox state of cells grown in serum-free Dulbecco's modified Eagle's/Ham's F12 medium (DMEM/F12). Concentrations (% v/v) causing 10-90% inhibition of the control assay responses were used for correlations with in vivo data. RESULTS: Cytotoxicities of contact lens solutions correlated better with irritant symptoms than with corneal staining, and were ranked as follows: Lens Plus << Opti-Free < or = ContaClair < or = ReNu. Lens Plus was not toxic to cell glycolysis, respiration, and proliferation for up to 20% v/v. However, the multi-purpose solutions inhibited these endpoints in a concentration-dependent manner. Opti-Free and ReNu, containing Dymed and Polyquad (ammonium surfactants), showed non-specific cell inhibition. The lactate production assay had a flatter log concentration-response curve than the other two assays. CONCLUSIONS: The proposed biochemically-based test battery using the target corneal epithelium has the potential to be a simple and effective method for screening and defining toxicity profiles of contact lens care solutions. The model can be applicable to small- or large-scale testing programs and research and development of new ocular products.