Genetic and epigenetic factors shape phenotypes and outcomes in systemic lupus erythematosus – focus on juvenile-onset systemic lupus erythematosus DOI Creative Commons
Amandine Charras, Linda T. Hiraki, Laura B. Lewandowski

et al.

Current Opinion in Rheumatology, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 11, 2024

Systemic lupus erythematosus (SLE) is a severe autoimmune/inflammatory disease. Patients with juvenile disease-onset and those of non-European ancestry are most severely affected. While the exact pathophysiology remains unknown, common rare gene variants in context environmental exposure epigenetic alterations involved. This manuscript summarizes current understanding genetic contributors to SLE risk, manifestations outcomes.

Language: Английский

Large-scale whole-exome sequencing analyses identified protein-coding variants associated with immune-mediated diseases in 350,770 adults DOI Creative Commons
Yang Liu,

Ya‐Nan Ou,

Bang‐Sheng Wu

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: July 15, 2024

Abstract The genetic contribution of protein-coding variants to immune-mediated diseases (IMDs) remains underexplored. Through whole exome sequencing 40 IMDs in 350,770 UK Biobank participants, we identified 162 unique genes 35 IMDs, among which 124 were novel genes. Several genes, including FLG is associated with atopic dermatitis and asthma, showed converging evidence from both rare common variants. 91 exerted significant effects on longitudinal outcomes (interquartile range Hazard Ratio: 1.12-5.89). Mendelian randomization five causal four approved drug targets ( CDSN , DDR1 LTA IL18BP ). Proteomic analysis indicated that mutations specific might also affect protein expression other IMDs. For example, DXO (celiac disease-related gene) PSMB9 (alopecia areata-related could modulate (autoimmune hypothyroidism-, psoriasis-, asthma-, Graves’ expression. Identified predominantly impact immune biochemical processes, can be clustered into pathways immune-related, urate metabolism, antigen processing. Our findings are the key pathogenesis provided new insights tailored innovative therapies.

Language: Английский

Citations

8
Multi-ancestry genome-wide meta-analysis with 472,819 individuals identifies 32 novel risk loci for psoriasis DOI Creative Commons
Min Zhang, Wenting Su, Jun Deng

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 30, 2025

Psoriasis is a common chronic, recurrent, immune-mediated disease involved in the skin or joints both. However, deeper insight into genetic susceptibility of psoriasis still unclear. Here we performed largest multi-ancestry meta-analysis genome-wide association study including 28,869 cases and 443,950 healthy controls. We identified 74 significant loci for psoriasis. Of loci, 32 were novel risk loci. Across 801 likely causal genes are indicated 164 prioritized. SNP-based heritability analyses demonstrated that variants explain 15% Gene-set correlation revealed psoriasis-related have positive correlations with autoimmune diseases such as ulcerative colitis, inflammatory bowel diseases, Crohn's disease. Gene-drug interaction analysis suggested psoriasis-associated overlapped targets current medications Finally, used to explore drug repurposing potential Based on provided new biological insights etiology clinical interest, gave some hints 76

Language: Английский

Citations

0
Shared Genetics in Celiac Disease and Inflammatory Bowel Disease Specify a Greater Role for Intestinal Epithelial Cells DOI Open Access
Nathan Vinícius Ribeiro,

Somaya Anwar,

Sebo Withoff

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 2982 - 2982

Published: March 25, 2025

The contribution of genetics to the development gut-related autoimmune diseases such as celiac disease (CeD) and inflammatory bowel (IBDs) is well-established, especially in immune cells, but pinpointing significance genetic variants other cell types more elusive. Increasing evidence indicates that intestinal epithelial cells are active players modulating response, suggesting affecting these could change behavior during disease. Moreover, fine-mapping causal genes relevant can help identify drug targets develop personalized targeted therapies. In this context, we reviewed functions disease-associated loci shared by CeD IBD expressed explored their potential impacts.

Language: Английский

Citations

0
Multi-ancestry sequencing-based genome-wide association study of C-reactive protein in 513,273 genomes DOI Creative Commons
Hongru Li, Jingyi Zhao,

Jinglan Dai

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 24, 2025

Language: Английский

Citations

0
Large-scale exome sequencing identified 18 novel genes for neuroticism in 394,005 UK-based individuals DOI
Xinrui Wu,

Ze-Yu Li,

Liu Yang

et al.

Nature Human Behaviour, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 7, 2024

Language: Английский

Citations

1
Advances in asthma and allergic disease genetics DOI
Nathan Schoettler

Current Opinion in Allergy and Clinical Immunology, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 6, 2024

Purpose of review Asthma and allergic disease are common chronic conditions affecting individuals all ages. The contribution genetics to the risk asthma diseases is well established, yet mechanisms through which genetic variation contribute continues be investigated. This focuses on recent advances made in studies phenotypes. Recent findings Progress has been at expanding more diverse non-European populations, associations have with loci refined phenotypes associated these conditions. Among 11 large genome-wide association or admixture mapping published recently, 52 novel were identified for As previous studies, variant- genome-based heritability remains relatively low. use polygenic scores increased reinforces remarkable overlap Whole genome exome sequencing led specific genes conditions, including rare STAT6 gain-of-function mutations that multiple, severe early life asthma. Summary Overall, we learned highly considerable their landscapes.

Language: Английский

Citations

0
Genetic Architecture of Postpartum Psychosis: From Common to Rare Genetic Variation DOI Creative Commons
Seulgi Jung, Madison Caballero, Adrianna P. Kępińska

et al.

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

Published: Dec. 10, 2024

Postpartum psychosis is a severe psychiatric condition marked by the abrupt onset of psychosis, mania, or psychotic depression following childbirth. Despite evidence for strong genetic basis, roles common and rare variation remain poorly understood. Leveraging data from Swedish national registers genomic All Us Research Program, we estimated family-based heritability at 55% WGS-based 37%, with an overrepresentation on X chromosome. Rare coding variant analysis identified DNMT1 HMGCR as potential risk genes (q < 0.1). Analysis 240,009 samples demonstrated significant associations between these multiple disorders, supporting their biological relevance. Additionally, 17% bipolar disorder, 21% schizophrenia, 16-25% autoimmune disorder overlapped postpartum psychosis. These findings reveal unique contributions shared pathways, providing foundation understanding pathophysiology advancing therapeutic strategies.

Language: Английский

Citations

0
Enhancing Clinical Applications by Evaluation of Sensitivity and Specificity in Whole Exome Sequencing DOI Open Access
Youngbeen Moon,

Chung Hwan Hong,

Young-Ho Kim

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(24), P. 13250 - 13250

Published: Dec. 10, 2024

The cost-effectiveness of whole exome sequencing (WES) remains controversial due to variant call variability, necessitating sensitivity and specificity evaluation. WES was performed by three companies (AA, BB, CC) using reference standards composed DNA from hydatidiform mole individual blood at various ratios. Sensitivity assessed the detection rate null–homozygote (N–H) alleles expected allelic fractions, while false positive (FP) errors were counted for unexpected alleles. approximately 20% in-house results BB CC around 5% AA. Dynamic Read Analysis GENomics (DRAGEN) analyses identified 1.34 1.71 times more variants, detecting over 96% with common variants increasing 5%. In-house FP varied significantly among (up 13.97 times), DRAGEN minimized this variation. Despite showing higher CC, increased highlights importance effective bioinformatic conditions. We also potential effects target enrichment proposed optimal cutoff values read depth allele fraction in WES. Optimizing analysis based on can enhance improve clinical utility

Language: Английский

Citations

0
Genetic and epigenetic factors shape phenotypes and outcomes in systemic lupus erythematosus – focus on juvenile-onset systemic lupus erythematosus DOI Creative Commons
Amandine Charras, Linda T. Hiraki, Laura B. Lewandowski

et al.

Current Opinion in Rheumatology, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 11, 2024

Systemic lupus erythematosus (SLE) is a severe autoimmune/inflammatory disease. Patients with juvenile disease-onset and those of non-European ancestry are most severely affected. While the exact pathophysiology remains unknown, common rare gene variants in context environmental exposure epigenetic alterations involved. This manuscript summarizes current understanding genetic contributors to SLE risk, manifestations outcomes.

Language: Английский

Citations

0