An integrative approach to identifying NPC1 as a susceptibility gene for gestational diabetes mellitus

The Journal of Maternal-Fetal & Neonatal Medicine, Journal Year: 2025, Volume and Issue: 38(1)

Published: Jan. 2, 2025

Objective The objective of this study was to identify a novel gene and its potential mechanisms associated with susceptibility gestational diabetes mellitus (GDM) through an integrative approach.

Language: Английский

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Cross-ancestry genome-wide association study identifies new susceptibility genes for preeclampsia

BMC Pregnancy and Childbirth, Journal Year: 2025, Volume and Issue: 25(1)

Published: April 1, 2025

Preeclampsia (PE) is a heterogeneous, multi-organ pregnancy disorder that poses significant health burden globally, with its pathogenesis remaining unclear. This study aimed to identify novel susceptibility genes for PE through cross-ancestry genome-wide association (GWAS). We performed meta-analysis summarize the GWAS data from United Kingdom, Finland, and Japan. Subsequently, multi-ancestry sum of single-effects model was used perform fine-mapping. The functional mapping annotation (FUMA)-expression quantitative trait loci (eQTL) method, transcriptome-wide (TWAS)- summary-based imputation (FUSION) complex analysis (GCTA)-multivariate set-based test (mBAT)-combo polygenic priority score (PoPS) method were employed screen candidate genes. utilized biomarker expression level using summary-level statistics (BLISS), based on protein (pQTL) data, conduct proteome-wide (PWAS) analysis, followed by drug prediction. Six associated risk identified: NPPA, SWAP70, NPR3, FGF5, REPIN1, ACAA1. High NPPA SWAP70 low reduced PE. Furthermore, we identified drugs target REPIN1. Our ACAA1 as whose predicted linked PE, offering new insights into genetic framework this condition.

Language: Английский

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Genetic causes of obesity: mapping a path forward

Trends in Molecular Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

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Multi-omics profiling reveals altered mitochondrial metabolism in adipose tissue from patients with metabolic dysfunction-associated steatohepatitis

EBioMedicine, Journal Year: 2024, Volume and Issue: 111, P. 105532 - 105532

Published: Dec. 27, 2024

Language: Английский

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The Gene Expression Landscape of Disease Genes

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 21, 2024

Fine-mapping and gene-prioritisation techniques applied to the latest Genome-Wide Association Study (GWAS) results have prioritised hundreds of genes as causally associated with disease. Here we leverage these recently compiled lists high-confidence causal interrogate where in body disease operate. Specifically, combine GWAS summary statistics, gene prioritisation expression RNA-seq data from 46 tissues 204 cell types relation 16 major diseases (including 8 cancers). In well-established relevance disease, typically higher absolute relative (i.e. tissue/cell specific) compared non-prioritised ‘control’ genes. Examples include brain psychiatric disorders ( P -value < 1×10 −7 ), microglia cells Alzheimer’s Disease = 9.8×10 −3 ) colon mucosa colorectal cancer ). We also observe significantly for multiple no established links corresponding While some may be explained by that span tissues, such macrophages brain, blood, lung spleen -values cause others is unclear motivates further investigation provide novel insights into etiology. For example, mammary tissue Type 2 Diabetes ); reproductive breast, uterus, vagina, prostate Coronary Artery −4 motor neurons 3×10 GTEx dataset, type predictor but contribution each (tissue, sample, subject, batch) varies widely among disease-associated Finally, highlight highest levels relevant guide functional follow-up studies. Our could offer involved initiation, inform drug target delivery strategies, highlighting potential off-target effects, exemplify performance different statistical tests linking expression.

Language: Английский

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Clinical and genetic association studies reveal within-individual variability as an integral part of Huntington disease

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 20, 2024

Abstract Huntington disease (HD) is one of the most common repeat expansion disorders. Clinically, HD patients exhibit considerable visit-to-visit variability in symptoms and signs independent measuring method or rater, yet neither precise nature nor determinants this clinical are known. Leveraging detailed genetic longitudinal data from large cohorts patients, work 1) establishes within-individual expression as an integral part semiology, demonstrating that it increases with duration, mutation size, younger age-at-onset, lower body weight, 2) provides a mathematical framework linking higher phenotypic to increased predictive entropy, revealing fundamental relation between energy expenditure, 3) identifies novel modifiers both age-at-onset HD. Thus, accounting for could facilitate discovery pathogenic mechanisms outcomes directly relevant development modifying therapies.

Language: Английский

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Prevalence and impact of a protein-truncating POMC variant on obesity in the Estonian Biobank

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 7, 2024

Population-specific genome-wide association studies can reveal high-impact genomic variants that influence traits like body-mass index (BMI). Using the Estonian Biobank BMI dataset (n=204,747 participants) we identified 214 significant loci. Among those hits, a common non-coding variant within newly associated ADGRL3 gene (-0.18 kg/m²; P = 3.06 × 10⁻⁹). Moreover, missense rare PTPRT:p.Arg1384His with lower (-0.44 2.5 10⁻¹⁰), while protein-truncating POMC:p.Glu206* was considerably higher (+0.81 1.5 10-12), both likely affecting functioning of leptin-melanocortin pathway. observed in different North-European populations, suggesting broader, yet elusive, distribution this damaging variant. These observations indicate novel roles and PTPRT genes body weight regulation suggest an increased prevalence European offering avenues for developing interventions obesity management.

Language: Английский

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Association of a Promoter DNA Methyltransferase 3 Gene Variant with DNA Methylation and Anthropometrics in Children from 4 to 12 Years Old

DNA, Journal Year: 2024, Volume and Issue: 4(3), P. 276 - 284

Published: Aug. 28, 2024

The global prevalence of obesity among adults, adolescents, and children has increased to alarming levels, making this disease a serious public health problem. etiology is complex multifactorial. Currently, epigenetic alterations are being investigated understand the mechanisms interaction between genes environmental behavioral risk factors involved in genesis obesity. In study, we examined association DNA methyltransferase 3 (DNMT3B) gene-149 C>T variant (rs2424913) genotypes with methylation changes anthropometric parameters cohort 171 followed from birth 12 years old. Genotypes were obtained using real-time polymerase chain reaction, was measured blood samples collected at 4 old through enzyme-linked immunosorbent assays. Our results showed that TT genotype associated an increase levels higher body mass index, waist circumference, subscapular subcutaneous fat, fat mass, lean basal metabolic rate years. suggest promoter DNMT3B gene can be relevant developing early age.

Language: Английский

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An integrative approach prioritizes the orphan GPR61 genomic region in tissue-specific regulation of chronotype

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 25, 2024

Chronotype, a manifestation of circadian rhythms, affects morning or evening preferences and ease getting-up. This study explores the genetic basis chronotype getting-up, focusing on G protein-coupled receptor locus, GPR61.

Language: Английский

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