Integrative analysis of relative abundance data and presence-absence data of the microbiome using the LDM

We previously developed LDM for testing hypotheses about the microbiome that performs the test at both the community level and the individual taxon level. LDM can be applied to relative abundance data and presence-absence data separately, which work well when associated taxa are abundant and rare, respectively. Here we propose an omnibus test based on LDM that allows simultaneous consideration of data at different scales, thus offering optimal power across scenarios with different association mechanisms. The omnibus test is available for the wide range of data types and analyses that are supported by LDM. The omnibus test has been added to the R package LDM, which is available on GitHub at https://github.com/yijuanhu/LDM .

Age, Body Mass Index (BMI) And Cognitive Difficulties In Appalachian West Virginia

Several known factors exacerbate the risk of cognitive difficulties among older adults. In addition to place-based disparities, body weight also predicts cognitive health. In fact, overweight and Obese BMI (Benito-Leon et al., 2013) and underweight BMI (Xiang & An, 2015) are risk factors for cognitive difficulties. Whether the effect of BMI operates similarly across age among adults facing place-based disparities is not clear. In order to better understand the role of BMI among adults already at-risk for health disparities, we used the 2018 BRFSS data to examine the relations among these variables among the 4817 West Virginian adults in the BRFSS database. Approximately 16.5% had difficulty making decisions or remembering. Approximately 73% were overweight or obese, 26% were healthy BMI, and 1% were underweight. A multinomial logistic regression was conducted to examine cognitive difficulties. Healthy BMI and ages 25 – 44 years were the reference groups. The omnibus test was significant, χ2 (5, N = 4817) = 38.71, p < 0.0001. Age and BMI uniquely contributed to the classification. Post hoc inspection of the Odds Ratios showed that adults ages 60 years and older with obesity were 1.27 times more likely to report cognitive difficulties, while those who were underweight were 3.74 times more likely to report cognitive difficulties. That individuals over age 60 with an obese or underweight BMI report more cognitive difficulties highlights the intersection among age, obesity and location on cognitive health disparities in West Virginia.

Pleiotropy of Alzheimer’s Disease and Educational Attainment: Insights from the Summary Statistics

Epidemiological studies report beneficial associations of higher educational attainment (EDU) with Alzheimer’s disease (AD). Prior genome-wide association studies (GWAS) also reported variants associated with AD and EDU separately. The analysis of pleiotropic predisposition to these phenotypes may shed light on EDU-related protection against AD. We examined pleiotropic predisposition to AD and EDU using Fisher’s method and omnibus test applied to summary statistics for single nucleotide polymorphisms (SNPs) associated with AD and EDU in large-scale univariate GWAS at suggestive-effect (5×10-8

Integrative eQTL-weighted hierarchical Cox models for SNP-set based time-to-event association studies

Background Integrating functional annotations into SNP-set association studies has been proven a powerful analysis strategy. Statistical methods for such integration have been developed for continuous and binary phenotypes; however, the SNP-set integrative approaches for time-to-event or survival outcomes are lacking. Methods We here propose IEHC, an integrative eQTL (expression quantitative trait loci) hierarchical Cox regression, for SNP-set based survival association analysis by modeling effect sizes of genetic variants as a function of eQTL via a hierarchical manner. Three p-values combination tests are developed to examine the joint effects of eQTL and genetic variants after a novel decorrelated modification of statistics for the two components. An omnibus test (IEHC-ACAT) is further adapted to aggregate the strengths of all available tests. Results Simulations demonstrated that the IEHC joint tests were more powerful if both eQTL and genetic variants contributed to association signal, while IEHC-ACAT was robust and often outperformed other approaches across various simulation scenarios. When applying IEHC to ten TCGA cancers by incorporating eQTL from relevant tissues of GTEx, we revealed that substantial correlations existed between the two types of effect sizes of genetic variants from TCGA and GTEx, and identified 21 (9 unique) cancer-associated genes which would otherwise be missed by approaches not incorporating eQTL. Conclusion IEHC represents a flexible, robust, and powerful approach to integrate functional omics information to enhance the power of identifying association signals for the survival risk of complex human cancers.

Associations between Personality Traits, Intolerance of Uncertainty, Coping Strategies, and Stress in Italian Frontline and Non-Frontline HCWs during the COVID-19 Pandemic—A Multi-Group Path-Analysis

The COVID-19 pandemic represented a very difficult physical and psychological challenge for the general population and even more for healthcare workers (HCWs). The main aim of the present study is to test whether there were significant differences between frontline and non-frontline Italian HCWs concerning (a) personality traits, intolerance of uncertainty, coping strategies and perceived stress, and (b) the models of their associations. A total of 682 Italian HCWs completed a self-report questionnaire: 280 employed in COVID-19 wards and 402 in other wards. The analysis of variance omnibus test revealed significant differences between the two groups only for perceived stress, which was higher among the frontline. The multi-group path analysis revealed significant differences in the structure of the associations between the two groups of HCWs, specifically concerning the relations between: personality traits and intolerance of uncertainty; intolerance of uncertainty and coping strategies. Regarding the relation between coping strategies and stress no difference was identified between the two groups. In both of them, emotionally focused coping was negatively related with perceived stress, whereas dysfunctional coping was positively related with stress. These results could be useful in planning actions aiming to reduce stress and improve the effectiveness of HCWs’ interventions. Training programs aimed to provide HCWs with a skillset to tackle uncertain and stressful circumstances could represent an appropriate support to develop a preventive approach during outbreaks.

ANALISIS FAKTOR-FAKTOR YANG MEMPENGARUHI AUDIT DELAY PELAPORAN KEUANGAN PADA PERUSAHAAN MANUFAKTUR YANG TERDAFTAR DI BURSA EFEK INDONESIA

Audit delay is a delay in submitting or publishing the company's financial statements which can make a financial report quality doubtful by the parties interested in making decisions. The purpose of this study is to test and analyze the effect of profitability, solvency, and KAP size on audit delay in financial report submission in consumer goods industrial sector manufacturing companies listed on the IDX for the period 2017 - 2019. In this study there are 3 independent variables, namely profitability. , solvency and hood size and the dependent variable there is 1, namely audit delay. The sampling method used in this research is purposive sampling method. The total population in this study were 36 companies and then eighteen (18) companies fulfilled the purposive sampling. The type of regression model used in this study is logistic regression, then to test the research in logistic regression using Statistical Product and Service Solution (SPSS) version 22.0 for windows using simultaneous test (Omnibus Test Of Model Coefficient) and Wald test (partial). The results in this study indicate that together (Simultaneous Test) all independent variables affect audit delay where the Chi-square value is 4.291 with a significance value of 0.032 <0.05, then the hypothesis is accepted. Then in the Wald Test only the KAP size variable affects audit delay significantly where the Wald test value is 2.068 with a significance of 0.048 <0.05, so the hypothesis is accepted. Meanwhile, the profitability and solvency variables have no effect on audit delay where the Wald test value is 0.663> 0.05 and 1.187> 0.05, so the hypothesis is rejected.

ANALISIS FAKTOR-FAKTOR YANG MEMPENGARUHI AUDIT DELAY

Setiap perusahaan yang tercatat di Bursa Efek Indonesia harus melaporkan laporan keuangannya kepada Otoritas Jasa Keuangan (OJK) setelah diaudit oleh auditor eksternal. Jika terlambat, maka akan dikenakan sanksi. Audit delay adalah lamanya waktu untuk menyelesaikan proses audit dari akhir tahun fiskal hingga tanggal diterbitkannya laporan audit. Tujuan penelitian ini adalah untuk mengetahui pengaruh pergantian auditor, reputasi KAP, opini audit dan komite audit terhadap audit delay pada perusahaan jasa transportasi yang terdaftar di Bursa Efek Indonesia tahun 2016-2019. Populasi penelitian ini adalah perusahaan jasa transportasi yang terdaftar di BEI tahun 2016–2019 sebanyak 45 perusahaan dengan teknik pengambilan sampel yaitu puposive sampling dan menghasilkan 27 perusahaan untuk diuji. Teknik analisis yang digunakan adalah analisis logistik. Hasil penelitian menunjukkan bahwa (1) pergantian auditor tidak berpengaruh terhadap audit delay dengan nilai β 0,089 dan nilai signifikansinya 0,875, (2) reputasi auditor tidak berpengaruh terhadap audit delay dengan nilai β -0,512 dan nilai signifikansinya 0,420, (3) opini audit berpengaruh negatif signifikan terhadap audit delay dengan nilai β -1.992 dan nilai signifikansinya 0,004, (4) komite audit tidak berpengaruh terhadap audit delay dengan nilai β 0,098 dan nilai signifikansinya 0,776, (5) Hasil uji simultan pada analisis ini menggunakan Omnibus Test yang menunjukkan bahwa semua variabel secara simultan berpengaruh signifikan terhadap audit delay dengan nilai signifikansinya 0,046.

AB0388 USE OF MESNA PROPHYLAXIS IN CYCLOPHOSPHAMIDE-TREATED PATIENTS WITH ANCA-ASSOCIATED VASCULITIS: RESULTS OF AN ELECTRONIC SURVEY

Background:Co-prescribing 2-mercaptoethane sodium sulfonate (mesna) with cyclophosphamide (CYC) for ANCA-associated vasculitis (AAV) aims to prevent the potential urotoxic effects of CYC. The evidence for this practice is often considered weak, and there may be some diversity in what practitioners do in clinical practice.Objectives:To investigate current clinical practice related to prescribing mesna prophylaxis or not and the underlying rationale for CYC-treated patients with AAV.Methods:We searched MEDLINE for publications with the MeSH term “ANCA-associated vasculitis” over a 10-year period up to October 2020. Email addresses of authors of these publications were extracted from the online information available in MEDLINE. These authors were invited by email to participate in an anonymous online SurveyMonkey survey of 21 to 24 questions asking about the characteristics of the respondent, their experience with AAV, and their practice in using CYC to treat AAV and using mesna in CYC-treated patients with AAV and the underlying rationale. Respondents were eligible to take the full survey if they were involved in deciding and/or monitoring therapy with CYC for patients with AAV. We compared 15 response variables to identify factors associated with the use or not of mesna. Response variables with multiple categories were first analyzed across all categories; if the omnibus test result was significant, additional analyses were used to identify the categories, which were the sources of group separation. We analyzed by-country variations for only countries with ≥ 10 respondents. Statistical analyses involved Pearson’s chi-square test or Fisher’s exact test, as appropriate. For multiple-response variables, the Rao-Scott correction was applied.Results:The invitation for the electronic survey was emailed twice in October 2020 to 1,374 unique email addresses; 156 individuals responded; 139 were eligible and completed the survey. The 139 participants were from 34 countries and were essentially MDs (98%) who mainly worked in rheumatology (50%), nephrology (25%) or internal medicine/clinical immunology (18%). Mesna was given in conjunction with CYC systematically, never, or on a case-by-case basis by 68%, 19% and 13% of respondents, respectively. As compared with systematic mesna-prescribers, never/occasional mesna-prescribers reported a longer time since receiving their degree as a health professional (≥ 15 years: 80% vs 50%, P<0.001), were more frequently based in England/United States (than in France/Germany/Italy) (78% vs 21%, P<0.001), had longer involvement in care of patients with AAV (≥ 15 years: 62% vs 37%, P=0.006), had less practice in using intermittent pulse therapy as the exclusive/predominant CYC administration scheme (62% vs 89%, P<0.001), and, as a rationale underpinning their mesna practice, had less adherence to local operational procedures (47% vs 73%, P=0.002) or (inter)national management guidelines for AAV (16% vs 49%, P<0.001). Never/occasional versus systematic use of mesna did not differ across medical specialties (5 categories, P=0.192) or healthcare settings (3 categories, P=0.437), and was not associated with prior experience of CYC-related urotoxic events (3 categories, P=0.495) or severe mesna toxicity issues (3 categories, P=0.957). The confidence that their practice reflected the best possible patient care did not differ between never/occasional and systematic mesna-prescribers (7-point Likert scale, P=0.794).Conclusion:Practice with regard to prescribing mesna in conjunction with CYC to treat AAV is heterogeneous, although systematic mesna use prevailed over never or occasional use. The decision to prescribe or not mesna may be based more on circumstantial than structural reasons.Disclosure of Interests:Lukas Joos: None declared, Solange Gonzalez Chiappe: None declared, Thomas Neumann Speakers bureau: GSK, Grant/research support from: Xifor, Alfred Mahr Speakers bureau: Amgen, Celgene, Roche, Chugai, Consultant of: Amgen, Celgene, Roche, Chugai

An Omnibus Test for Detecting Multiple Phenotype Associations Based on GWAS Summary Level Data

Abundant Genome-wide association study (GWAS) findings have reflected the sharing of genetic variants among multiple phenotypes. Exploring the association between genetic variants and multiple traits can provide novel insights into the biological mechanism of complex human traits. In this article, we proposed to apply the generalized Berk-Jones (GBJ) test and the generalized higher criticism (GHC) test to identify the genetic variants that affect multiple traits based on GWAS summary statistics. To be more robust to different gene-multiple traits association patterns across the whole genome, we proposed an omnibus test (OMNI) by using the aggregated Cauchy association test. We conducted extensive simulation studies to investigate the type one error rates and compare the powers of the proposed tests (i.e., the GBJ, GHC and OMNI tests) and the existing tests (i.e., the minimum of the p-values (MinP) and the cross-phenotype association test (CPASSOC) in a wide range of simulation settings. We found that all of these methods could control the type one error rates well and the proposed OMNI test has robust power. We applied those methods to the summary statistics dataset from Global Lipids Genetics Consortium and identified 19 new genetic variants that were missed by the original single trait association analysis.