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  • 1
    In: BMC Digital Health, Springer Science and Business Media LLC, Vol. 1, No. 1 ( 2023-02-03)
    Abstract: COVID-19 mortality prediction Background COVID-19 has become a major global public health problem, despite prevention and efforts. The daily number of COVID-19 cases rapidly increases, and the time and financial costs associated with testing procedure are burdensome. Method  To overcome this, we aim to identify immunological and metabolic biomarkers to predict COVID-19 mortality using a machine learning model. We included inpatients from Hong Kong’s public hospitals between January 1, and September 30, 2020, who were diagnosed with COVID-19 using RT-PCR. We developed three machine learning models to predict the mortality of COVID-19 patients based on data in their electronic medical records. We performed statistical analysis to compare the trained machine learning models which are Deep Neural Networks (DNN), Random Forest Classifier (RF) and Support Vector Machine (SVM) using data from a cohort of 5,059 patients (median age = 46 years; 49.3% male) who had tested positive for COVID-19 based on electronic health records and data from 532,427 patients as controls. Result  We identified top 20 immunological and metabolic biomarkers that can accurately predict the risk of mortality from COVID-19 with ROC-AUC of 0.98 (95% CI 0.96-0.98). Of the three models used, our result demonstrate that the random forest (RF) model achieved the most accurate prediction of mortality among COVID-19 patients with age, glomerular filtration, albumin, urea, procalcitonin, c-reactive protein, oxygen, bicarbonate, carbon dioxide, ferritin, glucose, erythrocytes, creatinine, lymphocytes, PH of blood and leukocytes among the most important biomarkers identified. A cohort from Kwong Wah Hospital (131 patients) was used for model validation with ROC-AUC of 0.90 (95% CI 0.84-0.92). Conclusion  We recommend physicians closely monitor hematological, coagulation, cardiac, hepatic, renal and inflammatory factors for potential progression to severe conditions among COVID-19 patients. To the best of our knowledge, no previous research has identified important immunological and metabolic biomarkers to the extent demonstrated in our study.
    Type of Medium: Online Resource
    ISSN: 2731-684X
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 3149807-3
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  • 2
    In: Genes, MDPI AG, Vol. 13, No. 6 ( 2022-05-27), p. 962-
    Abstract: (1) Background: Increasing evidence shows that sedentary behaviors are associated with neuropsychiatric disorders (NPDs) and thus may be a modifiable factor to target for the prevention of NPDs. However, the direction and causality for the relationship remain unknown; sedentary behaviors could increase or decrease the risk of NPDs, and/or NPDs may increase or decrease engagement in sedentary behaviors. (2) Methods: This Mendelian randomization (MR) study with two samples included independent genetic variants related to sedentary behaviors (n = 408,815), Alzheimer’s disease (AD; n = 63,926), schizophrenia (SCZ; n = 105,318), and major depressive disorder (MDD; n = 500,199), which were extracted from several of the largest non-overlapping genome-wide association studies (GWASs), as instrumental variables. The summarized MR effect sizes from each instrumental variable were combined in an IVW (inverse-variance-weighted) approach, with various approaches (e.g., MR-Egger, weighted median, MR-pleiotropy residual sum and outlier), and sensitivity analyses were performed to identify and remove outliers and assess the horizontal pleiotropy. (3) Results: The MR evidence and linkage disequilibrium score regression revealed a consistent directional association between television watching and MDD (odds ratio (OR), 1.13 for MDD per one standard deviation (SD) increase in mean television watching time; 95% CI, 1.06–1.20; p = 6.80 × 10−5) and a consistent relationship between computer use and a decrease in the risk of AD (OR, 0.52 for AD per one SD increase in mean computer use time; 95% CI, 0.32–0.84; p = 8.20 × 10−3). In the reverse direction, MR showed a causal association between a reduced risk of SCZ and an increase in driving time (β, −0.016; 95% CI, −0.027–−0.004; p = 8.30 × 10−3). (4) Conclusions: Using genetic instrumental variables identified from large-scale GWASs, we found robust evidence for a causal relationship between long computer use time and a reduced risk of AD, and for a causal relationship between long television watching time and an increased risk of MDD. In reverse analyses, we found that SCZ was causally associated with reduced driving time. These findings fit in with our observations and prior knowledge as well as emphasizing the importance of distinguishing between different domains of sedentary behaviors in epidemiologic studies of NPDs.
    Type of Medium: Online Resource
    ISSN: 2073-4425
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527218-4
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  • 3
    In: BMC Digital Health, Springer Science and Business Media LLC, Vol. 1, No. 1 ( 2023-09-12)
    Type of Medium: Online Resource
    ISSN: 2731-684X
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 3149807-3
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  • 4
    In: Journal of the Neurological Sciences, Elsevier BV, Vol. 440 ( 2022-09), p. 120335-
    Type of Medium: Online Resource
    ISSN: 0022-510X
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
    detail.hit.zdb_id: 1500645-1
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  • 5
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 132, No. suppl_3 ( 2015-11-10)
    Abstract: Cardiovascular disease (CVD) and type 2 diabetes mellitus (T2D) have many shared risk factors, suggesting that they have common pathophysiological mechanisms. Our recent analysis of genome wide association studies (GWAS) of both CVD and T2D in three ethnic populations revealed a number of biological pathways, such as extracellular matrix and focal adhesion, to be genetically associated with both diseases. Building on our prior work employing knowledge-driven pathways, we performed data-driven integrative genomics analyses using gene co-expression networks constructed from a multitude of tissue-specific transcriptome datasets in conjunction with GWAS for CVD, T2D, and a vascular disease phenotype (VD, representing combined CVD+T2D) in three different ethnic groups of 8155 African Americans, 3494 Hispanic Americans and 3697 Caucasian Americans participated in the national Women’s Health Initiative (WHI) study. We examined a total of 2674 coexpression networks and found that 24 modules were significantly enriched for GWAS signatures for all three disease end points (15 modules) or VD only (9 modules) across multiple cohorts at false discovery rate 〈 5%. These modules were enriched for the previously identified pathways like focal adhesion. Further, top modules for all three diseases were enriched for genes involved in citrate cycle and G-protein coupled receptor signaling, whereas top modules for VD were related to amino acid metabolism and BMP signaling, indicating novel processes that are shared between CVD and T2D. To pinpoint key driver (KD) for these modules, we integrated Bayesian networks of adipose, brain, kidney, liver and muscle tissue, and identified highly significant KDs such as BCL6B in adipose, MALAT1 in brain, ZNF565 in kidney, GLS2 in liver and MYL2 in muscle. Among the top KDs, MALAT1, GLS2 and MYL2 have been previously implicated in CVD and T2D, whereas the others represented novel findings. In summary, by leveraging multi-ethnic GWAS data on CVD and T2D and data-driven transcriptional networks, we uncovered both known and novel regulatory mechanisms that appeared to be shared by the two vascular diseases. These network regulators revealed may serve as important targets for future experimental validation.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2015
    detail.hit.zdb_id: 1466401-X
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  • 6
    In: Nature Genetics, Springer Science and Business Media LLC, Vol. 53, No. 6 ( 2021-06), p. 840-860
    Type of Medium: Online Resource
    ISSN: 1061-4036 , 1546-1718
    RVK:
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 1494946-5
    SSG: 12
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  • 7
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Genetics Vol. 13 ( 2022-6-21)
    In: Frontiers in Genetics, Frontiers Media SA, Vol. 13 ( 2022-6-21)
    Abstract: Introduction: Gestational diabetes mellitus (GDM), heart disease (HD) and high body mass index (BMI) are strongly related to Alzheimer’s disease (AD) dementia in pregnant women. Therefore, we aimed to determine the total effects of GDM, heart disease, and high BMI on maternal AD dementia. Methods: We used data from the genome-wide association studies of European populations including more than 30,000 participants. We performed two-sample Mendelian randomization (MR) and multivariable MR (MVMR) to systematically estimate the direct effects of GDM, HD, and high BMI on maternal AD and dementia. Multiple sensitivity analyses involving classical MR approaches and expanded MR-pleiotropy residual sum and outlier analysis. Results: In two-sample MR analysis, the inverse-variance weighted method in our study demonstrated no significant causality between GDM and maternal dementia ( β = −0.006 ± 0.0026, p = 0.82). This method also revealed no significant causality between high BMI and maternal dementia ( β = 0.0024 ± 0.0043, p = 0.57), and it was supported by the MR-Egger regression results, which showed no causal effect of high BMI on maternal Alzheimer’s disease and dementia ( β = 0.0027 ± 0.0096, p = 0.78). The IVW method showed no significant causal relationship between maternal HD and maternal Alzheimer’s disease and dementia ( β = −0.05 ± 0.0042, p = 0.117) and MR-Egger regression analysis gave a similar result ( β = −0.12 ± 0.0060, p = 0.079). In MVMR analysis, we found no significant causal relationship between GDM, high BMI, or HD and maternal Alzheimer’s disease and dementia ( p = 0.94, 0.82, and 0.13, respectively). Thus, the MVMR estimates were consistent with our results from the two-sample MR analysis. We confirmed that these results showed no horizontal pleiotropy and enhanced the robustness of our results through multiple sensitivity analyses. Conclusion: In two-sample MR analysis, we found no significant causal relationship between GDM, HD, high BMI and maternal AD and dementia. These results differed from previous observational studies showing HD is a significant predictor of dementia. MVMR analysis supported no significant causal relationship between GDM, HD, high BMI and maternal AD and dementia. Sensitivity analysis broadly increased the robustness of two-sample MR and MVMR analysis results.
    Type of Medium: Online Resource
    ISSN: 1664-8021
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606823-0
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  • 8
    In: The FASEB Journal, Wiley, Vol. 35, No. 7 ( 2021-07)
    Type of Medium: Online Resource
    ISSN: 0892-6638 , 1530-6860
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 1468876-1
    SSG: 12
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  • 9
    In: Clinical Chemistry, Oxford University Press (OUP), Vol. 69, No. 4 ( 2023-04-03), p. 374-385
    Abstract: The role of sex hormone-binding globulin (SHBG) levels in clinical risk stratification and intervention for coronary heart disease (CHD) remains uncertain. We aimed to examine whether circulating levels of SHBG are predictive of CHD risk in men and women. Methods We investigated the association between SHBG and the risk of incident CHD in 128 322 men and 135 103 women free of CHD at baseline in the prospective United Kingdom Biobank (UKB) cohort. The unconfounded associations were estimated using Mendelian randomization (MR) analysis. We further conducted a meta-analysis to integrate currently available prospective evidence. CHD events included nonfatal and fatal myocardial infarction and coronary revascularization. Results In the UKB, during a median of 11.7 follow-up years, 10 405 men and 4512 women developed CHD. Serum levels of SHBG were monotonically associated with a decreased risk of CHD in both men (adjusted hazard ratio [HR] per log nmol/L increase in SHBG: 0.88 [0.83–0.94] ) and women (HR: 0.89 [0.83–0.96]). MR-based analyses suggested causality and a dose-response relationship of SHBG with CHD risk. A cumulative meta-analysis including 216 417 men and 138 282 women from 11 studies showed that higher levels of SHBG were prospectively associated with decreased CHD risk in men comparing the highest with the lowest quartile: pooled relative risk (RR) 0.81 (0.74–0.89) and women (pooled RR: 0.86 [0.78–0.94] ). Conclusions Higher circulating SHBG levels were directly and independently predictive of lower CHD risk in both men and women. The utility of SHBG for CHD risk stratification and prediction warrants further study.
    Type of Medium: Online Resource
    ISSN: 0009-9147 , 1530-8561
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
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  • 10
    In: Diabetes, American Diabetes Association, Vol. 66, No. 4 ( 2017-04-01), p. 935-947
    Abstract: Some Shanghai Clinical Center f a role of Niemann-Pick type C1 (NPC1) for obesity traits. However, whether the loss-of-function mutations in NPC1 cause adiposity in humans remains unknown. We recruited 25 probands with rare autosomal-recessive Niemann-Pick type C (NP-C) disease and their parents in assessment of the effect of heterozygous NPC1 mutations on adiposity. We found that male NPC1+/− carriers had a significantly higher BMI than matched control subjects or the whole population-based control subjects. Consistently, male NPC1+/− mice had increased fat storage while eating a high-fat diet. We further conducted an in-depth assessment of rare variants in the NPC1 gene in young, severely obese subjects and lean control subjects and identified 17 rare nonsynonymous/frameshift variants in NPC1 (minor allele frequency & lt;1%) that were significantly associated with an increased risk of obesity (3.40% vs. 0.73%, respectively, in obese patients and control subjects, P = 0.0008, odds ratio = 4.8, 95% CI 1.7–13.2), indicating that rare NPC1 variants were enriched in young, morbidly obese Chinese subjects. Importantly, participants carrying rare variants with severely damaged cholesterol-transporting ability had more fat accumulation than those with mild/no damage rare variants. In summary, rare loss-of-function NPC1 mutations were identified as being associated with human adiposity with a high penetrance, providing potential therapeutic interventions for obesity in addition to the role of NPC1 in the familial NP-C disease.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2017
    detail.hit.zdb_id: 1501252-9
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