Microvascular and macrovascular complications of type 2 diabetes mellitus: Exome wide association analyses

Frontiers in Endocrinology, Год журнала: 2023, Номер 14

Опубликована: Март 23, 2023

Type 2 diabetes mellitus (T2DM) is a chronic, metabolic disorder in which concomitant insulin resistance and β-cell impairment lead to hyperglycemia, influenced by genetic environmental factors. T2DM associated with long-term complications that have contributed the burden of morbidity mortality worldwide. The objective this manuscript conduct an Exome-Wide Association Study (EWAS) on Emirati individuals improve our understanding diabetes-related early diagnostic methods treatment strategies.

Язык: Английский

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Genetic evidence for causal effects of immune dysfunction in psychiatric disorders: where are we?

Translational Psychiatry, Год журнала: 2024, Номер 14(1)

Опубликована: Янв. 26, 2024

Abstract The question of whether immune dysfunction contributes to risk psychiatric disorders has long been a subject interest. To assert this hypothesis plethora correlative evidence accumulated from the past decades; however, variety technical and practical obstacles impeded on cause-effect interpretation these data. With advent large-scale omics technology advanced statistical models, particularly Mendelian randomization, new studies testing old are accruing. Here we synthesize findings genomics genetic causal inference role in major reconcile data with pre-omics findings. By reconciling evidences, aim identify key gaps propose directions for future field.

Язык: Английский

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Genome data based deep learning identified new genes predicting pharmacological treatment response of attention deficit hyperactivity disorder

Translational Psychiatry, Год журнала: 2025, Номер 15(1)

Опубликована: Фев. 7, 2025

Although the efficacy of pharmacy in treatment attention deficit/hyperactivity disorder (ADHD) has been well established, lack predictors response poses great challenges for personalized treatment. The current study employed a comprehensive approach, combining genome-wide association analyses (GWAS) and deep learning (DL) methods, to elucidate genetic underpinnings pharmacological ADHD. Based on genotype data medication-naïve patients with ADHD who received treatments 12 weeks, performed GWAS using percentage changes ADHD-RS score as phenotype. Then, DL models were constructed predict symptom scores variants selected based four different P thresholds (E-02, E-03, E-04, E-05) inputs. results identified two significant loci (rs10880574, = 2.39E-09; rs2000900, 3.31E-09) which implicated genes, TMEM117 MYO5B, that primarily associated both brain- gut-related disorders. convolutional neural network (CNN) model, values less than E-02 (5516 SNPs), demonstrated best performance mean squared error (MSE) equals 0.012 (Accuracy 0.83; Sensitivity 0.90; Specificity 0.75) validation dataset, 0.081 an independent test dataset (Acc 0.61, 0.81; 0.26). Notably, variant contributed most CNN model was NKAIN2, ADHD-related gene, is also metabolic processes. To conclude, integration methods revealed new genes contribute responses, underscored interplay between systems processes, potentially providing critical insights into precision Furthermore, our exhibited good encouraged future studies implied potential clinical applications.

Язык: Английский

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Physical Activity, Sedentary Behavior, and Type 2 Diabetes: Mendelian Randomization Analysis

Journal of the Endocrine Society, Год журнала: 2023, Номер 7(8)

Опубликована: Июнь 26, 2023

The causality and pathways of the associations between physical activity inactivity risk type 2 diabetes remain inconclusive.

Язык: Английский

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Variants at the Interleukin 1 Gene Locus and Pericarditis

JAMA Cardiology, Год журнала: 2023, Номер 9(2), С. 165 - 165

Опубликована: Дек. 27, 2023

Importance Recurrent pericarditis is a treatment challenge and often debilitating condition. Drugs inhibiting interleukin 1 cytokines are promising new option, but their use based on scarce biological evidence clinical trials of modest sizes, the contributions innate adaptive immune processes to pathophysiology incompletely understood. Objective To human genomics, transcriptomics, proteomics shed light pathogenesis pericarditis. Design, Setting, Participants This was meta-analysis genome-wide association studies from 5 countries. Associations were examined between pericarditis-associated variants subtypes (including recurrent pericarditis) secondary phenotypes. explore mechanisms, associations with messenger RNA expression ( cis -eQTL), plasma protein levels (pQTL), CpG methylation DNA (ASM-QTL) assessed. Data Iceland (deCODE genetics, 1983-2020), Denmark (Copenhagen Hospital Biobank/Danish Blood Donor Study, 1977-2022), UK (UK Biobank, 1953-2021), US (Intermountain, 1996-2022), Finland (FinnGen, 1970-2022) included. analyzed September 2022 August 2023. Exposure Genotype. Main Outcomes Measures Pericarditis. Results In this study 4894 individuals (mean [SD] age at diagnosis, 51.4 [17.9] years, 2734 [67.6%] male, excluding FinnGen cohort), identified 2 independent common intergenic locus chromosome 2q14. The lead variant rs12992780 (T) (effect allele frequency [EAF], 31%-40%; odds ratio [OR], 0.83; 95% CI, 0.79-0.87; P = 6.67 × 10 −16 ), downstream IL1B rs7575402 (A or T) (EAF, 45%-55%; adjusted OR, 0.89; 0.85-0.93; 9.6 −8 ). had smaller for (0.76) than acute form (0.86) heterogeneity .03) associated overlapping binding sites 4 transcription factors known regulate production: PU.1 (encoded by SPI1 STAT1, STAT3, CCAAT/enhancer-binding β CEBPB Conclusions Relevance found an sequence gene locus. finding has potential contribute development more targeted personalized therapy 1–blocking drugs.

Язык: Английский

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A genome-wide association study of high-sensitivity C-reactive protein in a large Korean population highlights its genetic relationship with cholesterol metabolism

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 2, 2025

Язык: Английский

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Genetic insights into CRP levels in Indian adolescents: confirming adult genetic associations

Molecular Genetics and Genomics, Год журнала: 2025, Номер 300(1)

Опубликована: Янв. 23, 2025

Язык: Английский

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Lymphocyte-C-reactive protein ratio upon admission to predict disease progression and ICU admission in adult patients with diabetic ketoacidosis

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 23, 2025

This study aimed to investigate whether lymphocyte-C-reactive protein ratio (LCR) upon admission can predict disease progression and intensive care unit (ICU) in adult patients with diabetic ketoacidosis (DKA). A single-center retrospective was conducted, including DKA admitted the First Affiliated Hospital of Harbin Medical University between March 2018 2023. Multiple demographic clinical data were collected from medical records during hospitalization. Subsequently, sequential organ failure assessment (SOFA) score LCR calculated based on relevant parameters within 24 h admission. These indicators compared among different severity groups, factors related severe DKA, concurrent acute kidney injury (AKI), ICU further analyzed. Receiver operating characteristic (ROC) curve analysis performed determine sensitivity, specificity, area under ROC (AUC), cut-off value LCR. total 271 enrolled categorized into three groups: mild group (n = 42), moderate 64), 165). Significant differences observed these groups. Glasgow coma scale (GCS) score, LCR, pH, bicarbonate (HCO3-) identified as protective for DKA. Conversely, SOFA neutrophil count (NEUT), serum creatinine (SCr), glucose (GLU) risk AKI. Concurrent AKI admission, while pH a factor. The areas (AUC) classify group, 0.679, 0.718, 0.621, respectively, 212.80, 96.16, 63.35, sensitivity 54.8%, 76.4%, 78.9%, specificity 76.0%, 62.4%, 46.3%. provides great potential

Язык: Английский

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Enhanced insights into the genetic architecture of 3D cranial vault shape using pleiotropy-informed GWAS

Communications Biology, Год журнала: 2025, Номер 8(1)

Опубликована: Март 15, 2025

Abstract Large-scale GWAS studies have uncovered hundreds of genomic loci linked to facial and brain shape variation, but only tens associated with cranial vault shape, a largely overlooked aspect the craniofacial complex. Surrounding neocortex, plays central role during development understanding its genetics are pivotal for conditions. Experimental biology prior genetic generated wealth knowledge that presents opportunities aid further discovery efforts. Here, we use conditional FDR method leverage data bone mineral density enhance SNP shape. This approach identified 120 independent at 1% FDR, nearly tripling number discovered through unconditioned analysis implicating crucial transcription factors signaling pathways. These results significantly advance our more broadly.

Язык: Английский

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Gene clusters linked to insulin resistance identified in a genome-wide study of the Taiwan Biobank population

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Апрель 14, 2025

Язык: Английский

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