Haptoglobin 2-2 genotype is associated with increased risk of cardiovascular disease in patients with rheumatoid arthritis: a matched case-control study.

Introduction: Traditional risk factors do not fully explain the increased risk of cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA). The 2-2 genotype confers a lower anti-oxidant and higher inflammatory effect on the vasculature compared to the non- 2-2 genotype. This study investigates the association of the genotype with CVD in patients with RA.

Exome sequencing of Singapore Chinese anti-citrullinated-protein-antibody-positive rheumatoid arthritis patients.

Objective: More than 130 susceptibility loci for rheumatoid arthritis (RA) have been identified with genome-wide association studies (GWAS). To investigate the genetic predisposition of Chinese anti-cyclic-citrullinated-peptides-antibody-positive RA, we carried out an exome sequencing study.

Methods: Patients were recruited from three major public hospitals in Singapore, Tan Tock Seng Hospital (TTSH), Singapore General Hospital and National University Health System.

The axis of complement C1 and nucleolus in antinuclear autoimmunity.

Antinuclear autoantibodies (ANA) are heterogeneous self-reactive antibodies that target the chromatin network, the speckled, the nucleoli, and other nuclear regions. The immunological aberration for ANA production remains partially understood, but ANA are known to be pathogenic, especially, in systemic lupus erythematosus (SLE). Most SLE patients exhibit a highly polygenic disease involving multiple organs, but in rare complement C1q, C1r, or C1s deficiencies, the disease can become largely monogenic.

Dual rheumatoid factor and anti-cyclic citrullinated peptide antibody positivity affects the manifestations of rheumatoid arthritis.

Introduction: Rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA) are used in the diagnosis and prognostication of rheumatoid arthritis (RA). We wanted to determine the specific contributions of RF and ACPA to the biological nature of RA and whether they act synergistically.

Methods: We identified 731 patients from our prospective multi-ethnic RA cohort and categorised them into four groups: ACPA-positive, RF-positive, doubly positive and doubly negative.

A five-safes approach to a secure and scalable genomics data repository.

Genomic researchers increasingly utilize commercial cloud service providers (CSPs) to manage data and analytics needs. CSPs allow researchers to grow Information Technology (IT) infrastructure on demand to overcome bottlenecks when combining large datasets. However, without adequate security controls, the risk of unauthorized access may be higher for data stored on the cloud.

The Singapore National Precision Medicine Strategy.

Precision medicine promises to transform healthcare for groups and individuals through early disease detection, refining diagnoses and tailoring treatments. Analysis of large-scale genomic-phenotypic databases is a critical enabler of precision medicine. Although Asia is home to 60% of the world's population, many Asian ancestries are under-represented in existing databases, leading to missed opportunities for new discoveries, particularly for diseases most relevant for these populations.

Analysis of clinically relevant variants from ancestrally diverse Asian genomes.

Asian populations are under-represented in human genomics research. Here, we characterize clinically significant genetic variation in 9051 genomes representing East Asian, South Asian, and severely under-represented Austronesian-speaking Southeast Asian ancestries. We observe disparate genetic risk burden attributable to ancestry-specific recurrent variants and identify individuals with variants specific to ancestries discordant to their self-reported ethnicity, mostly due to cryptic admixture.

and testing for thiopurine therapy: A major tertiary hospital experience and lessons learned.

Variants in thiopurine methyltransferase () and nudix hydrolase 15 () are associated with an accumulation of cytotoxic metabolites leading to increased risk of drug-related toxicity with standard doses of thiopurine drugs. We established and genetic testing for clinical use and evaluated the utilization, service outcomes and potential value of multi-gene PGx testing for 210 patients that underwent pharmacogenetics (PGx) testing for thiopurine therapy with the aim to optimize service delivery for future prescribing. The test was most commonly ordered for Gastroenterology (40.

Pregnancy loss and the risk of rheumatoid arthritis in Chinese women: findings from the China Kadoorie biobank.

Considering the female preponderance of rheumatoid arthritis (RA), and disease onset typically after the reproductive years, pregnancy and childbirth may play a role in the aetiology of the disease. Adverse outcomes of pregnancy have been found to precede the diagnosis of autoimmune diseases, including RA, but the evidence is scant and inconsistent. Therefore, we investigate whether pregnancy loss is associated with the risk of RA in Chinese women.

Evaluation of Patients with Vaccine Allergies Prior to mRNA-Based COVID-19 Vaccination.

During the initial rollout of coronavirus disease 2019 (COVID-19) vaccination in Singapore, the Ministry of Health (MOH) issued a recommendation that patients with a history of any previous vaccine allergy be referred to an allergist for further review of their suitability to proceed with mRNA-based COVID-19 vaccines. Patients fulfilling the above criterion were divided into three groups: immediate reaction (Group A), delayed reaction (Group B) and no/irrelevant reaction (Group C). They were subjected to either a skin prick test (SPT) and intradermal test (IDT) with polyethylene glycol (PEG) or polysorbate-containing products; direct injection with the Pfizer BNT162b2 vaccine in the allergy clinic; or injection at community vaccination centres, respectively.

Missense variant in interleukin-6 signal transducer identified as susceptibility locus for rheumatoid arthritis in Chinese patients.

Objectives: This study aims to uncover variants of large effect size and allele frequency below 5% by sequencing all extant genes associated with rheumatoid arthritis (RA) in a homogeneous patient cohort.

Patients And Methods: This retrospective study was conducted between January 2001 and December 2017. We selected Chinese RA patients positive for anti-citrullinated peptide antibody (ACPA).

Machine learning using genetic and clinical data identifies a signature that robustly predicts methotrexate response in rheumatoid arthritis.

Objective: To develop a hypothesis-free model that best predicts response to MTX drug in RA patients utilizing biologically meaningful genetic feature selection of potentially functional single nucleotide polymorphisms (pfSNPs) through robust machine learning (ML) feature selection methods.

Methods: MTX-treated RA patients with known response were divided in a 4:1 ratio into training and test sets. From the patients' exomes, potential features for classifier prediction were identified from pfSNPs and non-genetic factors through ML using recursive feature elimination with cross-validation incorporating the random forest classifier.

The impact of diabetes mellitus on treatment and outcomes of rheumatoid arthritis at 5-year follow-up: results from a multi-ethnic Asian cohort.

Objectives: We evaluated the impact of type 2 diabetes mellitus (T2DM) on RA treatment and outcomes in a longitudinal RA cohort.

Methods: We analysed data collected in the period 2001-2013 involving 583 RA patients, including demographics, diabetes diagnosis, clinical features, treatment, ACR functional class, HAQ, and quality-of-life measurement using the Short-Form 36.

Results: Seventy-seven (13.

Metabolic syndrome and its effect on the outcomes of rheumatoid arthritis in a multi-ethnic cohort in Singapore.

Introduction: Over-expression of common inflammatory mediators in the metabolic syndrome (MetS) and in rheumatoid arthritis (RA) may lead to mutually adverse outcomes.

Aim: We investigate the prevalence of MetS in a multi-ethnic population of RA patients and its effect on clinical and patient-reported outcomes.

Method: Six hundred sixty RA (561 women) patients from a public-sector specialist clinic in a hospital in Singapore were assessed for MetS according to the 2009 Joint Consensus (JC) and the 2004 National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) definitions.

DUBStepR is a scalable correlation-based feature selection method for accurately clustering single-cell data.

Feature selection (marker gene selection) is widely believed to improve clustering accuracy, and is thus a key component of single cell clustering pipelines. Existing feature selection methods perform inconsistently across datasets, occasionally even resulting in poorer clustering accuracy than without feature selection. Moreover, existing methods ignore information contained in gene-gene correlations.

Pseudo-Anaphylactic Reactions to Pfizer BNT162b2 Vaccine: Report of 3 Cases of Anaphylaxis Post Pfizer BNT162b2 Vaccination.

Anaphylactic reactions were observed after Singapore's national coronavirus disease 2019 (COVID-19) vaccination programme started in December 2020. We report the clinical and laboratory features of three patients in our institution who developed anaphylactic reactions after receiving the Pifzer BNT162b2 vaccine. IgM and IgG antibodies, but not IgE antibodies to the Pfizer BNT162b2 vaccine, were detected in all subjects.

Comparison of mental-physical comorbidity, risk of death and mortality among patients with mental disorders - A retrospective cohort study.

Aim: To compare the risk of death, the prevalence of comorbid chronic physical illness and mortality among an Asian population of patients with mental disorders.

Methods: This was a retrospective data analysing of medical records of patients with schizophrenia, depression, anxiety, bipolar disorder, alcohol use disorder (AUD) or substance use disorder and the comorbid chronic physical illnesses. The hazard risk of death was calculated with Cox regression and compared between patients with and without comorbid chronic physical illness(es).

Conversion among the 28-joint count activity indices for rheumatoid arthritis.

Objective: Disease activity indices for rheumatoid arthritis (RA) are important in clinical practice and research. Although they are closely correlated, they are not in good agreement. We derived formulae to convert values from one of the four 28-joint count indices (disease activity score using erythrocyte sedimentation rate [DAS28-ESR], disease activity score using C-reactive protein [DAS28-CRP], clinical disease activity index [CDAI], and simple disease activity index [SDAI]) to any of the others.

Clinical utility of anti-DFS70 for identifying antinuclear antibody-positive patients without systemic autoimmune rheumatic disease.

Introduction: The antinuclear antibody (ANA) test is a screening test for systemic autoimmune rheumatic disease (SARD). We hypothesised that the presence of anti-DFS70 in ANA-positive samples was associated with a false-positive ANA test and negatively associated with SARD.

Methods: A retrospective analysis of patient samples received for ANA testing from 1 January 2016 to 30 June 2016 was performed.

Large-Scale Whole-Genome Sequencing of Three Diverse Asian Populations in Singapore.

Underrepresentation of Asian genomes has hindered population and medical genetics research on Asians, leading to population disparities in precision medicine. By whole-genome sequencing of 4,810 Singapore Chinese, Malays, and Indians, we found 98.3 million SNPs and small insertions or deletions, over half of which are novel.