Polygenic risk scores (PRS) have attenuated cross-population predictive performance. As existing genomewide association studies (GWAS) were predominantly conducted in individuals of European descent, the limited transferability of PRS reduces its clinical value in non-European populations and may exacerbate healthcare disparities. Recent efforts to level ancestry imbalance in genomic research have expanded the scale of non-European GWAS, although they remain under-powered. Here we present a novel PRS construction method, PRS-CSx, which improves cross-population polygenic prediction by integrating GWAS summary statistics from multiple populations. PRS-CSx couples genetic effects across populations via a shared continuous shrinkage prior, enabling more accurate effect size estimation by sharing information between summary statistics and leveraging linkage disequilibrium (LD) diversity across discovery samples, while inheriting computational efficiency and robustness from PRS-CS. We show that PRS-CSx outperforms alternative methods across traits with a wide range of genetic architectures and cross-population genetic correlations in simulations, and substantially improves the prediction of quantitative traits and schizophrenia risk in non-European populations.
BACKGROUND & AIMS: Q6Although coronavirus disease 2019 (COVID-19) is characterized by fever and respiratory symptoms, some patients have no or mild symptoms. Severe acute respiratory syndromecoronavirus (SARS-CoV-2) has been detected in feces of patients. We investigated gastrointestinal symptoms and shedding of virus into feces of patients with asymptomatic or mild COVID-19. METHODS:We collected data from 46 patients (median age, 26 y; 46% men) with asymptomatic or mild COVID-19 (without fever and pneumonia) and prolonged respiratory shedding of SARS-CoV-2, quarantined from April 4, 2020, through April 24, 2020, in Korea. Respiratory specimens included upper respiratory specimens (nasopharyngeal and oropharyngeal swabs) and lower respiratory specimens (sputum), and were collected twice per week. The median interval between COVID-19 diagnosis to the start of fecal sample collection was 37 days (range, 29-41 d); 213 stool specimens were collected from 46 patients. We used real-time reverse-transcription polymerase chain reaction to detect SARS-CoV-2 in the respiratory and fecal specimens. RESULTS:Gastrointestinal manifestations were observed in 16 of the 46 patients (35%); diarrhea was the most common (15%), followed by abdominal pain (11%), dyspepsia (11%), and nausea (2%).Virus RNA was detected in feces from 2 patients without gastrointestinal symptoms (4%). Mean cycle threshold values from the time of quarantine to the time of fecal collection tended to be lower in patients with virus detected in fecal samples than in patients without virus in fecal samples (29.91 vs 33.67 in the first week, 29.47 vs 35.71 in the fifth week, respectively). Shedding of virus into feces persisted until day 50 after diagnosis; fecal samples began to test negative before or at approximately the time that respiratory specimens also began to test negative. CONCLUSIONS:In an analysis of fecal and respiratory specimens from patients with COVID-19 in quarantine in Korea, we found that the gastrointestinal tract could be a route of transmission of SARS-CoV-2 even in patients with asymptomatic or mild disease, with no gastrointestinal symptoms. The viral load of the respiratory specimens appears be related to shedding of the virus into feces in this group of patients.
Objectives: To investigate antibody production in asymptomatic and mild COVID-19 patients. Methods: Sera from asymptomatic to severe COVID-19 patients were collected. Microneutralization (MN), fluorescence immunoassay (FIA), and enzyme-linked immunosorbent assay (ELISA) were performed. Results: A total of 70 laboratory-confirmed COVID-19 patients were evaluated, including 15 asymptomatic/anosmia, 49 mild symptomatic, and 6 pneumonia patients. The production of the neutralizing antibody was observed in 100% of pneumonia, 93.9% of mild symptomatic, and 80.0% of asymptomatic/anosmia groups. All the patients in the pneumonia group showed high MN titer (≥1:80), while 36.7% of mild symptomatic and 20.0% of asymptomatic/anosmia groups showed high titer (p < 0.001). Anti-SARS-CoV-2 antibodies could be more sensitively detected by FIA IgG (98.8%) and ELISA (97.6%) in overall. For the FIA IgG test, all patients in the pneumonia group exhibited a high COI value (≥15.0), while 89.8% of mild symptomatic and 73.3% of asymptomatic/anosmia groups showed a high value (p = 0.049). For the ELISA test, all patients in the pneumonia group showed a high optical density (OD) ratio (≥3.0), while 65.3% of mild symptomatic and 53.3% of asymptomatic/anosmia groups showed a high ratio (p = 0.006). Conclusions: Most asymptomatic and mild COVID-19 patients produced the neutralizing antibody, although the titers were lower than pneumonia patients. ELISA and FIA sensitively detected anti-SARS-CoV-2 antibodies.
In this large cohort of apparently healthy Korean adults, HBsAg seropositivity was associated with lower risk of developing NAFLD, indicating a possible effect of HBV infection on the pathogenesis of NAFLD development. (Hepatology 2017;65:828-835).
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