Multi-ancestry polygenic risk scores for the prediction of type 2 diabetes and complications in diverse ancestries.

Background: Polygenic risk scores (PRSs) improve type 2 diabetes (T2D) prediction beyond clinical risk factors but perform poorly in non-European populations, where T2D burden is often higher, undermining their global clinical utility.

Methods: We conducted the largest global effort to date to harmonize T2D genome-wide association study (GWAS) meta-analyses across five ancestries-European (EUR), African/African American (AFR), Admixed American (AMR), South Asian (SAS), and East Asian (EAS)-including 360,000 T2D cases and 1·8 million controls (41% non-EUR). We constructed ancestry-specific and multi-ancestry PRSs in training datasets including 11,000 T2D cases and 32,000 controls, and validated their performance in independent datasets including 39,000 T2D cases and 126,000 controls of diverse ancestries.

Dietary Habits, TCM Constitutions, and Obesity: Investigating the Protective Effects of Vegetarian Dietary Patterns in Taiwan.

Obesity is a global health challenge associated with metabolic and cardiovascular diseases. Traditional Chinese Medicine (TCM) body constitution theory offers a unique perspective on individual susceptibility to obesity; however, its integration into public health strategies remains underexplored. To examine the associations between vegetarian dietary patterns, TCM body constitution types (Phlegm stasis, Yang deficiency, and Yin deficiency), and overweight/obesity in a large-scale national cohort.

Clinical impact of pharmacogenetic risk variants in a large chinese cohort.

Incorporating pharmacogenetics into clinical practice promises to improve therapeutic outcomes by optimizing drug selection and dosage based on genetic factors affecting drug response. A key advantage of PGx-guided therapy is to decrease the likelihood of adverse events. To evaluate the clinical impact of PGx risk variants, we performed a retrospective study using genetic and clinical data from the largest Han Chinese cohort, comprising 486,956 individuals, assembled by the Taiwan Precision Medicine Initiative.

Kidney multiome-based genetic scorecard reveals convergent coding and regulatory variants.

Kidney dysfunction is a major cause of mortality, but its genetic architecture remains elusive. In this study, we conducted a multiancestry genome-wide association study in 2.2 million individuals and identified 1026 (97 previously unknown) independent loci.

Polygenic height prediction for the Han Chinese in Taiwan.

Human height prediction based on genetic factors alone shows positive correlation, but predictors developed for one population perform less well when applied to population of different ancestries. In this study, we evaluated the utility of incorporating non-genetic factors in height predictors for the Han Chinese population in Taiwan. We analyzed data from 78,719 Taiwan Biobank (TWB) participants and 40,641 Taiwan Precision Medicine Initiative (TPMI) participants using genome-wide association study and multivariable linear regression least absolute shrinkage and selection operator (LASSO) methods to incorporate genetic and non-genetic factors for height prediction.

Role of IL3RA in a Family with Lumbar Spinal Stenosis.

Lumbar spinal stenosis (LSS) is a degenerative spinal condition characterized by the narrowing of the spinal canal, resulting in low back pain (LBP) and limited leg mobility. Twin and family studies have suggested that genetics contributes to disease progression. However, the genetic causes of familial LSS remain unclear.

An Approach to Identifying Spatial Variability in Observed Infectious Disease Spread in a Prospective Time-Space Series with Applications to COVID-19 and Dengue Incidence.

Most of the growing prospective analytic methods in space-time disease surveillance and intended functions of disease surveillance systems focus on earlier detection of disease outbreaks, disease clusters, or increased incidence. The spread of the virus such as SARS-CoV-2 has not been spatially and temporally uniform in an outbreak. With the identification of an infectious disease outbreak, recognizing and evaluating anomalies (excess and decline) of disease incidence spread at the time of occurrence during the course of an outbreak is a logical next step.

Multi-ancestry genome-wide study in >2.5 million individuals reveals heterogeneity in mechanistic pathways of type 2 diabetes and complications.

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes. To characterise the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study (GWAS) data from 2,535,601 individuals (39.7% non-European ancestry), including 428,452 T2D cases.

A Functional Polymorphism Downstream of Vitamin A Regulator Gene Is Associated with Hand Osteoarthritis.

While genetic analyses have revealed ~100 risk loci associated with osteoarthritis (OA), only eight have been linked to hand OA. Besides, these studies were performed in predominantly European and Caucasian ancestries. Here, we conducted a genome-wide association study in the Han Chinese population to identify genetic variations associated with the disease.

Levonorgestrel intrauterine devices improve body constitution deviations in the perspective of traditional Chinese medicine and quality of life in patients with chronic pelvic pain and heavy menstrual bleeding.

Objective: This study aimed to investigate whether the use of levonorgestrel intrauterine devices (LNG-IUD) in the perspective of traditional Chinese medicine (TCM) can improve the body constitution deviations and quality of life (QoL) in patients with chronic pelvic pain (CPP) and heavy menstrual bleeding (HMB).

Materials And Methods: To understand the TCM body constitution differences between patients, patients with CPP from a gynecology clinic were first compared to a healthy control group from the Academia Sinica Taiwan Biobank (TWB). Patients with CPP were also compared with patients with pelvic diseases from the TWB.

Enrichment of Prevotella intermedia in human colorectal cancer and its additive effects with Fusobacterium nucleatum on the malignant transformation of colorectal adenomas.

Background: Owing to the heterogeneity of microbiota among individuals and populations, only Fusobacterium nucleatum and Bacteroides fragilis have been reported to be enriched in colorectal cancer (CRC) in multiple studies. Thus, the discovery of additional bacteria contributing to CRC development in various populations can be expected. We aimed to identify bacteria associated with the progression of colorectal adenoma to carcinoma and determine the contribution of these bacteria to malignant transformation in patients of Han Chinese origin.

Cardio- and Neurotoxicity of Selected Anti-COVID-19 Drugs.

Since December 2019, the novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected ~435 million people and caused ~6 million related deaths as of March 2022. To combat COVID-19, there have been many attempts to repurpose FDA-approved drugs or revive old drugs. However, many of the current treatment options have been known to cause adverse drug reactions.

Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation.

We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 × 10), which were delineated to 338 distinct association signals.

Spatially varying effects of measured confounding variables on disease risk.

Background: The presence of considerable spatial variability in incidence intensity suggests that risk factors are unevenly distributed in space and influence the geographical disease incidence distribution and pattern. As most human common diseases that challenge investigators are complex traits and as more factors associated with increased risk are discovered, statistical spatial models are needed that investigate geographical variability in the association between disease incidence and confounding variables and evaluate spatially varying effects on disease risk related to known or suspected risk factors. Information on geography that we focus on is geographical disease clusters of peak incidence and paucity of incidence.

Genetic factors of idiopathic central precocious puberty and their polygenic risk in early puberty.

Objective,: To investigate the genetic characteristics of idiopathic central precocious puberty (ICPP) and validate its polygenic risk for early puberty.

Design And Methods: A bootstrap subsampling and genome-wide association study were performed on Taiwanese Han Chinese girls comprising 321 ICPP patients and 148 controls. Using previous GWAS data on pubertal timing, a replication study was performed.

Genetic risk score constructed from common genetic variants is associated with cardiovascular disease risk in type 2 diabetes mellitus.

Background: Patients with type 2 diabetes mellitus (T2DM) experience a two-fold increased risk of cardiovascular diseases. Genome-wide association studies (GWAS) have identified T2DM susceptibility genetic variants. Interestingly, the genetic variants associated with cardiovascular disease risk in T2DM Han Chinese remain to be elucidated.

Genome-Wide and Candidate Gene Association Analyses Identify a 14-SNP Combination for Hypertension in Patients With Type 2 Diabetes.

Background: High blood pressure is common and comorbid with type 2 diabetes (T2D). Almost 50% of patients with T2D have high blood pressure. Patients with both conditions of hypertension (HTN) and T2D are at risk for cardiovascular diseases and mortality.