Schizophrenia (SCZ) is a chronic mental illness and among the most debilitating conditions encountered in medical practice. A recent landmark SCZ study of the protein-coding regions of the genome identified a causal role for ten genes and a concentration of rare variant signals in evolutionarily constrained genes1. This recent study—and most other large-scale human genetics studies—was mainly composed of individuals of European (EUR) ancestry, and the generalizability of the findings in non-EUR populations remains unclear. To address this gap, we designed a custom sequencing panel of 161 genes selected based on the current knowledge of SCZ genetics and sequenced a new cohort of 11,580 SCZ cases and 10,555 controls of diverse ancestries. Replicating earlier work, we found that cases carried a significantly higher burden of rare protein-truncating variants (PTVs) among evolutionarily constrained genes (odds ratio = 1.48; P = 5.4 × 10−6). In meta-analyses with existing datasets totaling up to 35,828 cases and 107,877 controls, this excess burden was largely consistent across five ancestral populations. Two genes (SRRM2 and AKAP11) were newly implicated as SCZ risk genes, and one gene (PCLO) was identified as shared by individuals with SCZ and those with autism. Overall, our results lend robust support to the rare allelic spectrum of the genetic architecture of SCZ being conserved across diverse human populations.

Schizophrenia is a chronic mental illness that is amongst the most debilitating conditions encountered in medical practice. A recent landmark schizophrenia study of the protein-coding regions of the genome identified a causal role for ten genes and a concentration of rare variant signals in evolutionarily constrained genes1. This study -- and most other large-scale human genetic studies -- was mainly composed of individuals of European ancestry, and the generalizability of the findings in non-European populations is unclear. To address this gap in knowledge, we designed a custom sequencing panel based on current knowledge of the genetic architecture of schizophrenia and applied it to a new cohort of 22,135 individuals of diverse ancestries. Replicating earlier work, cases carried a significantly higher burden of rare protein-truncating variants among constrained genes (OR=1.48, p-value = 5.4 x 10-6). In meta-analyses with existing schizophrenia datasets totaling up to 35,828 cases and 107,877 controls, this excess burden was largely consistent across five continental populations. Two genes (SRRM2 and AKAP11) were newly implicated as schizophrenia risk genes, and one gene (PCLO) was identified as a shared risk gene for schizophrenia and autism. Overall, our results lend robust support to the rare allelic spectrum of the genetic architecture of schizophrenia being conserved across diverse human populations.

Background: To determine the prevalence of bacterial vaginosis among females of reproductive age and assessment of the effectiveness of pH and the Whiff test in its diagnosis. Methods: This was a cross-sectional study. A total of 100 subjects were included, coming with a complaint of vaginal discharge. The bacterial vaginosis was diagnosed by using the Nugent scoring system, Whiff and pH tests. The prevalence was calculated by descriptive statistics and using the Chi-square test and results were shown in percentages and mean with standard deviation. Results: The estimated prevalence of bacterial vaginosis among the local population of females of child-bearing age was found to be 39%. The mean age of females with bacterial vaginosis was 33.33±10.46 years. The Whiff test was positive in 89.74% cases, while pH was elevated in 94.87% females with bacterial vaginosis. Conclusion: Bacterial vaginosis is a frequent cause of vaginal discharge in females of reproductive age in Pakistan. The diagnosis can be easily made by using Whiff and pH tests even at resource-poor settings. Keywords: Bacterial vaginosis, Child-bearing age, pH test, Whiff test.

Introduction Globally, 80% of the burdenof major depressive disorder (MDD) pertains to low- and middle-income countries. Research into genetic and environmental risk factors has the potential to uncover disease mechanisms that may contribute to better diagnosis and treatment of mental illness, yet has so far been largely limited to participants with European ancestry from high-income countries. The DIVERGE study was established to help overcome this gap and investigate genetic and environmental risk factors for MDD in Pakistan. Methods DIVERGE aims to enrol 9000 cases and 4000 controls in hospitals across the country. Here, we provide the rationale for DIVERGE, describe the study protocol and characterise the sample using data from the first 500 cases. Exploratory data analysis is performed to describe demographics, socioeconomic status, environmental risk factors, family history of mental illness and psychopathology. Results and discussion Many participants had severe depression with 74% of patients who experienced multiple depressive episodes. It was a common practice to seek help for mental health struggles from faith healers and religious leaders. Socioeconomic variables reflected the local context with a large proportion of women not having access to any education and the majority of participants reporting no savings. Conclusion DIVERGE is a carefully designed case–control study of MDD in Pakistan that captures diverse risk factors. As the largest genetic study in Pakistan, DIVERGE helps address the severe underrepresentation of people from South Asian countries in genetic as well as psychiatric research.