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Abstract To elucidate the specific and shared genetic background of schizophrenia (SCZ) and bipolar disorder (BPD), this study explored the association of polygenic liabilities for SCZ and BPD with educational attainment and cognitive aging. Among 106,806 unrelated community participants from the Taiwan Biobank, we calculated the polygenic risk score (PRS) for SCZ (PRSSCZ) and BPD (PRSBPD), shared PRS between SCZ and BPD (PRSSCZ+BPD), and SCZ-specific PRS (PRSSCZvsBPD). Based on the sign-concordance of the susceptibility variants with SCZ/BPD, PRSSCZ was split into PRSSCZ_concordant/PRSSCZ_discordant, and PRSBPD was split into PRSBPD_concordant/PRSBPD_discordant. Ordinal logistic regression models were used to estimate the association with educational attainment. Linear regression models were used to estimate the associations with cognitive aging (n = 27,005), measured by the Mini-Mental State Examination (MMSE), and with MMSE change (n = 6194 with mean follow-up duration of 3.9 y) in individuals aged≥ 60 years. PRSSCZ, PRSBPD, and PRSSCZ+BPD were positively associated with educational attainment, whereas PRSSCZvsBPD was negatively associated with educational attainment. PRSSCZ was negatively associated with MMSE, while PRSBPD was positively associated with MMSE. The concordant and discordant parts of polygenic liabilities have contrasting association, PRSSCZ_concordant and PRSBPD_concordant mainly determined these effects mentioned above. PRSSCZvsBPD predicted decreases in the MMSE scores. Using a large collection of community samples, this study provided evidence for the contrasting effects of polygenic architecture in SCZ and BPD on educational attainment and cognitive aging and suggested that SCZ and BPD were not genetically homogeneous.

Abstract Background It has been proposed that having a psychiatric disorder could increase the risk of developing a gastrointestinal disorder, and vice versa. The role of familial coaggregation and shared genetic loading between psychiatric and gastrointestinal disorders remains unclear. Methods This study used the Taiwan National Health Insurance Research Database; 4,504,612 individuals born 1970–1999 with parental information, 51,664 same-sex twins, and 3,322,959 persons with full-sibling(s) were enrolled. Genotyping was available for 106,796 unrelated participants from the Taiwan Biobank. A logistic regression model was used to examine the associations of individual history, affected relatives, and polygenic risk scores (PRS) for schizophrenia (SCZ), bipolar disorder (BPD), major depressive disorder (MDD), and obsessive-compulsive disorder (OCD), with the risk of peptic ulcer disease (PUD), gastroesophageal reflux disease (GERD), irritable bowel syndrome (IBS), and inflammatory bowel disease (IBD), and vice versa. Results Here we show that parental psychiatric disorders are associated with gastrointestinal disorders. Full-siblings of psychiatric cases have an increased risk of gastrointestinal disorders except for SCZ/BPD and IBD; the magnitude of coaggregation is higher in same-sex twins than in full-siblings. The results of bidirectional analyses mostly remain unchanged. PRS for SCZ, MDD, and OCD are associated with IBS, PUD/GERD/IBS/IBD, and PUD/GERD/IBS, respectively. PRS for PUD, GERD, IBS, and IBD are associated with MDD, BPD/MDD, SCZ/BPD/MDD, and BPD, respectively. Conclusions There is familial coaggregation and shared genetic etiology between psychiatric and gastrointestinal comorbidity. Individuals with psychiatric disorder-affected relatives or with higher genetic risk for psychiatric disorders should be monitored for gastrointestinal disorders, and vice versa.

Abstract Background Most studies have focused on the risk factors, treatment, and care of affective psychosis, and several have reported a relationship between ambient air quality and this psychosis. Although an association has been reported between psychosis and genes, studies mainly explored the associations between one type of psychosis and one gene; few have identified genes related to affective psychosis. This study investigates the genetic and environmental factors of affective psychosis. Methods In this retrospective longitudinal study, 27 604 participants aged 30–70 were selected from Taiwan Biobank. The participants’ propensity scores were calculated based on their demographic information, and propensity score matching was performed to divide the participants into an experimental (i.e., affective psychosis) and control group at a 1:5 ratio. Plink was used to analyze the major and minor types of gene expression related to affective psychosis, and PM2.5 exposure was incorporated into the analyses. Results According to the generalized estimating equation analysis results, 8 single nucleotide polymorphisms (SNPs) belonging to the ANK3, BDNF, CACNA1C, and GRID1 genotypes were significantly correlated with depressive disorder (P

Rationale & Objective: We aimed to study the comparative effectiveness of percutaneous coronary intervention with drug-eluting stent and coronary artery bypass grafting in patients receiving dialysis. Study Design: This was a retrospective observational cohort study. Setting & Participants: This population-based study identified patients receiving dialysis hospitalized for coronary revascularization between January 1, 2009 and December 31, 2015, in the Taiwan National Health Insurance Research Database. Exposures: Patients received percutaneous coronary intervention with drug-eluting stent versus coronary artery bypass grafting. Outcomes: The study outcomes were all-cause mortality, in-hospital mortality, and repeat revascularization. Analytical Approach: Propensity scores were used to match patients. Cox proportional hazards models and logistic regression models were constructed to examine associations between revascularization strategies and mortality. Interval Cox models were fitted to estimate time-varying hazards during different periods. Results: A total of 1,840 propensity score-matched patients receiving dialysis were analyzed. Coronary artery bypass grafting was associated with higher in-hospital mortality (coronary artery bypass grafting vs percutaneous coronary intervention with drug-eluting stent; crude mortality rate 12.5% vs 3.3%; adjusted OR, 5.22; 95% CI, 3.42-7.97; P

ABSTRACTAcinetobacter baumannii emerged as one of the most important pathogens that causes nosocomial infections due to its increased multidrug resistance. Identifying capsular epidemiology in A. baumannii can aid in the development of effective treatments and preventive measures against this emerging pathogen. Here we established a wzc-based method, and combined it with wzy-PCR to determine capsular types of A. baumannii causing nosocomial bacteraemia collected at two medical centres in Taiwan from 2015 to 2017. Among the 237 patients with A. baumannii bacteraemia, 98 (41.4%) isolates were resistant to carbapenems. Four prevalent capsular types (KL2, KL10, KL22, and KL52) accounted for 84.7% of carbapenem-resistant A. baumannii (CRAB) and 12.2% of non-CRAB. The rate of pneumonia, intensive care unit admission, APACHE II score, and Pitt bacteraemia score were higher in patients with KL2/10/22/52 infection than in those with non-KL2/10/22/52 infection. Patients with KL2/10/22/52 infection and patients with CRAB infection have a higher cumulative incidence of attributable and all-cause in-hospital 30-day mortality. On multivariate analysis, appropriate empirical antimicrobial therapy within 24 h was associated with a lower risk of 30-day attributable mortality in the KL2/10/22/52 isolates (odds ratio = 0.19, 95% CI: 0.06–0.66, p = 0.008) but not in non-KL2/10/22/52 isolates. Early recognition of carbapenem resistance-associated capsular types may help clinicians to promptly implement appropriate antimicrobial therapy for improving the outcomes in patients with CRAB bacteraemia.

Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce mortality in patients with cancer, especially breast cancer, but their influence on second cancer risk is uncertain. This study aimed to examine whether NSAID use is associated with second cancer risk in patients with breast cancer. This population-based propensity score-matched cohort study using Taiwan’s National Health Insurance Research Database enrolled patients with newly diagnosed breast cancer (n = 7356) with and without (n = 1839) NSAID therapy from 2000 to 2009. They were followed up until the diagnosis of second cancer, death, or end of 2011. Cox proportional hazard models were used to estimate adjusted hazard ratios (aHR). The NSAID cohort had a lower incidence rate of second cancer than the non-NSAID cohort (5.57 vs. 9.19 per 1,000 person-years), with an aHR of 0.63 (95% confidence interval (CI) 0.46–0.87). When compared with the non-NSAID cohort, the second cancer incidence was lower in patients taking non-cyclooxygenase 2 inhibitors (aHR 0.67, 95% CI 0.47–0.94) and in those receiving multiple NSAIDs during follow-up (aHR 0.55, 95% CI 0.37–0.84). A dose–response relationship existed in NSAID cumulative days. The findings demonstrate that NSAID use reduces second cancer risk in a dose-dependent manner in patients with primary breast cancer.

Abstract An earlier age at onset (AAO) has been associated with greater genetic loadings in schizophrenia. This study aimed to identify modifier loci associated with an earlier AAO of schizophrenia. A genome-wide association analysis (GWAS) was conducted in 94 schizophrenia probands with the earliest AAO and 91 with the latest AAO. Candidate single nucleotide polymorphisms (SNPs) were then genotyped in the co-affected siblings and unrelated probands. Multi-SNP genetic risk scores (GRS) composed of the candidate loci were used to distinguish patients with an early or late AAO. The 14-SNP GRS could distinguish the co-affected siblings (n = 90) of the earliest probands from those (n = 91) of the latest probands. When 132 patients with an earlier AAO and 158 patients with a later AAO were included, a significant trend in the 14-SNP GRS was detected among those unrelated probands from 4 family groups with the earliest, earlier, later, and latest AAO. The overall effect of the 14 SNPs on an AAO in schizophrenia was verified using co-affected siblings of the GWAS probands and trend effect across unrelated patients. Preliminary network analysis of these loci revealed the involvement of PARK2, a gene intensively reported in Parkinson’s disease and schizophrenia research.

Abstract Background Both adolescent substance use and adolescent depression are major public health problems, and have the tendency to co-occur. Thousands of articles on adolescent substance use or depression have been published. It is labor intensive and time consuming to extract huge amounts of information from the cumulated collections. Topic modeling offers a computational tool to find relevant topics by capturing meaningful structure among collections of documents. Methods In this study, a total of 17,723 abstracts from PubMed published from 2000 to 2014 on adolescent substance use and depression were downloaded as objects, and Latent Dirichlet allocation (LDA) was applied to perform text mining on the dataset. Word clouds were used to visually display the content of topics and demonstrate the distribution of vocabularies over each topic. Results The LDA topics recaptured the search keywords in PubMed, and further discovered relevant issues, such as intervention program, association links between adolescent substance use and adolescent depression, such as sexual experience and violence, and risk factors of adolescent substance use, such as family factors and peer networks. Using trend analysis to explore the dynamics of proportion of topics, we found that brain research was assessed as a hot issue by the coefficient of the trend test. Conclusions Topic modeling has the ability to segregate a large collection of articles into distinct themes, and it could be used as a tool to understand the literature, not only by recapturing known facts but also by discovering other relevant topics.

Background Medical treatment should be tailored to an individual's characteristics to optimize treatment benefits. We examined whether case‐only analyses from spontaneous reporting systems can detect host‐medication interactions in oral antidiabetic drug‐associated myocardial infarction. Methods and Results Interaction between sex and use of oral antidiabetic drugs was mined among patients with myocardial infarction in the US Food and Drug Administration Adverse Event Reporting System from 2004 to 2014, including 55 718 males and 42 428 females. The odds ratio (OR) of multiplicative interactions was used to estimate sex‐drug interaction. Detected signs of these interactions were then validated by a nested case‐control study utilizing a healthcare record database, Taiwan's National Health Insurance Research Database, from 2001 to 2014, including 31 585 cases and 126 340 controls. In the US Food and Drug Administration Adverse Event Reporting System, a higher proportion of male than female patients used metformin (10.32% in males versus 7.82% in females) and sulfonylureas (4.75% in males versus 3.43% in females); after adjusting for patients’ pharmacy‐based chronic disease score, males had a higher risk of metformin‐associated (OR=1.07; 99% confidence interval, 1.00–1.14) and sulfonylureas‐associated (OR=1.21; 99% confidence interval, 1.10–1.33) myocardial infarction than females. Detected signs of sex‐drug interactions were validated in the National Health Insurance Research Database (OR for metformin=1.14; 99% confidence interval, 1.03–1.26; OR for sulfonylureas=1.13; 99% confidence interval, 1.02–1.25). Conclusions Males have a higher risk of metformin‐ and sulfonylureas‐associated myocardial infarction than females, which suggests that sex‐drug interactions are a key issue in diabetes mellitus treatment plan development. This case‐only approach using information from spontaneous reporting systems may be a potential tool for screening host‐medication interactions that cause adverse events.

Genes, environment, and the interaction between them are each known to play an important role in the risk for developing complex diseases such as metabolic syndrome. For environmental factors, most studies focused on the measurements observed at the individual level, and therefore can only consider the gene-environment interaction at the same individual scale. Indeed the group-level (called contextual) environmental variables, such as community factors and the degree of local area development, may modify the genetic effect as well. To examine such cross-level interaction between genes and contextual factors, a flexible statistical model quantifying the variability of the genetic effects across different categories of the contextual variable is in need. With a Bayesian generalized linear mixed-effects model with an unconditional likelihood, we investigate whether the individual genetic effect is modified by the group-level residential environment factor in a matched case-control metabolic syndrome study. Such cross-level interaction is evaluated by examining the heterogeneity in allelic effects under various contextual categories, based on posterior samples from Markov chain Monte Carlo methods. The Bayesian analysis indicates that the effect of rs1801282 on metabolic syndrome development is modified by the contextual environmental factor. That is, even among individuals with the same genetic component of PPARG_Pro12Ala, living in a residential area with low availability of exercise facilities may result in higher risk. The modification of the group-level environment factors on the individual genetic attributes can be essential, and this Bayesian model is able to provide a quantitative assessment for such cross-level interaction. The Bayesian inference based on the full likelihood is flexible with any phenotype, and easy to implement computationally. This model has a wide applicability and may help unravel the complexity in development of complex diseases.

Background: The co-occurrence of depression and diabetes mellitus has been linked to an increased risk of developing cancer. This study aimed to investigate whether depression further amplifies the risk of cancer among individuals with diabetes., Methods: This population-based matched cohort study utilized Taiwan's National Health Insurance claims database. A total of 85,489 newly diagnosed diabetic patients with depressive disorders were selected, along with 427,445 comparison subjects. The matching process involved age, sex, and the calendar year of diabetes onset. The average follow-up duration for the two cohorts was 6.4 and 6.5 years, respectively. The primary outcome of interest was the occurrence of overall cancer or cancer at specific anatomical sites., Results: The adjusted hazard ratios for overall cancer incidence were 1.08 (95% CI, 1.05-1.11). For site-specific cancers, depression exhibited significant associations with oropharyngeal, esophageal, liver, gynecological, prostate, kidney, and hematologic malignancies among patients with diabetes. Notably, a severity-response relationship was observed, indicating that patients with recurrent episodes of major depressive disorders exhibited a higher incidence of cancer compared to those diagnosed with dysthymia or depressive disorder not otherwise specified. Furthermore, the strength of the association between depression and cancer risk was more pronounced among younger patients with diabetes as opposed to older adults. However, no significant relationship was observed between adherence to antidepressant treatment and cancer risk., Conclusions: The findings of this study indicate a significant association between depression and an elevated risk of cancer among individuals diagnosed with diabetes. Future investigations should replicate our findings, explore the effects of pharmacological and non-pharmacological treatments on cancer risk, and identify the underlying mechanisms., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)