DNA methylation as a possible causal mechanism linking childhood adversity and health: Results from two-sample mendelian randomization study DOI
Isabel K. Schuurmans, Erin C. Dunn, Alexandre A. Lussier

et al.

American Journal of Epidemiology, Journal Year: 2024, Volume and Issue: 193(11), P. 1541 - 1552

Published: May 17, 2024

Abstract Childhood adversity is an important risk factor for adverse health across the life course. Epigenetic modifications, such as DNA methylation (DNAm), are a hypothesized mechanism linking to disease susceptibility. Yet, few studies have determined whether adversity-related DNAm alterations causally related future outcomes or if their developmental timing plays role in these relationships. Here, we used 2-sample mendelian randomization obtain stronger causal inferences about association between adversity-associated loci development (ie, birth, childhood, adolescence, and young adulthood) 24 mental, physical, behavioral outcomes. We identified particularly strong associations attention-deficit/hyperactivity disorder, depression, obsessive-compulsive suicide attempts, asthma, coronary artery disease, chronic kidney disease. More of were birth childhood DNAm, whereas adolescent adulthood more closely linked mental health. also had primarily risk-suppressing relationships with outcomes, suggesting that might reflect compensatory buffering mechanisms against rather than acting solely indicator risk. Together, our results suggest both physical impacts differences emerging earlier development.

Language: Английский

Proteome-wide Mendelian randomization in global biobank meta-analysis reveals multi-ancestry drug targets for common diseases DOI Creative Commons
Huiling Zhao,

Humaria Rasheed,

Therese Haugdahl Nøst

et al.

Cell Genomics, Journal Year: 2022, Volume and Issue: 2(11), P. 100195 - 100195

Published: Oct. 12, 2022

Proteome-wide Mendelian randomization (MR) shows value in prioritizing drug targets Europeans but with limited evidence other ancestries. Here, we present a multi-ancestry proteome-wide MR analysis based on cross-population data from the Global Biobank Meta-analysis Initiative (GBMI). We estimated putative causal effects of 1,545 proteins eight diseases African (32,658) and European (1,219,993) ancestries identified 45 7 protein-disease pairs genetic colocalization two ancestries, respectively. A comparison both seven specific separately. Integrating these signals clinical trial evidence, prioritized 16 for investigation future trials. Our results highlight informing generalizability disease prevention across illustrate meta-analysis biobanks development.

Language: Английский

Citations

52
Loci for insulin processing and secretion provide insight into type 2 diabetes risk DOI Creative Commons
K. Alaine Broadaway, Xianyong Yin, Alice Williamson

et al.

The American Journal of Human Genetics, Journal Year: 2023, Volume and Issue: 110(2), P. 284 - 299

Published: Jan. 23, 2023

Language: Английский

Citations

28
Genetics of chronic respiratory disease DOI
Ian Sayers, Catherine John, Jing Chen

et al.

Nature Reviews Genetics, Journal Year: 2024, Volume and Issue: 25(8), P. 534 - 547

Published: March 6, 2024

Language: Английский

Citations

13
Analytical challenges in omics research on asthma and allergy: A National Institute of Allergy and Infectious Diseases workshop DOI
Supinda Bunyavanich, Patrice M. Becker, Matthew C. Altman

et al.

Journal of Allergy and Clinical Immunology, Journal Year: 2024, Volume and Issue: 153(4), P. 954 - 968

Published: Jan. 29, 2024

Language: Английский

Citations

9
AI-enhanced integration of genetic and medical imaging data for risk assessment of Type 2 diabetes DOI Creative Commons
Yijia Huang, Chun‐Houh Chen, Hsin‐Chou Yang

et al.

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

Published: May 18, 2024

Abstract Type 2 diabetes (T2D) presents a formidable global health challenge, highlighted by its escalating prevalence, underscoring the critical need for precision strategies and early detection initiatives. Leveraging artificial intelligence, particularly eXtreme Gradient Boosting (XGBoost), we devise robust risk assessment models T2D. Drawing upon comprehensive genetic medical imaging datasets from 68,911 individuals in Taiwan Biobank, our integrate Polygenic Risk Scores (PRS), Multi-image (MRS), demographic variables, such as age, sex, T2D family history. Here, show that model achieves an Area Under Receiver Operating Curve (AUC) of 0.94, effectively identifying high-risk subgroups. A streamlined featuring eight key variables also maintains high AUC 0.939. This accuracy promises to catalyze preventive strategies. Moreover, introduce accessible online tool T2D, facilitating broader applicability dissemination findings.

Language: Английский

Citations

9
Functional characterization of eQTLs and asthma risk loci with scATAC-seq across immune cell types and contexts DOI

Julong Wei,

Justyna Resztak, Ali Ranjbaran

et al.

The American Journal of Human Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

1
Integration of functional genomics and statistical fine-mapping systematically characterizes adult-onset and childhood-onset asthma genetic associations. DOI Creative Commons
Xiaoyuan Zhong,

Robert D. Mitchell,

Christine Billstrand

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 17, 2025

Abstract Background Genome-wide association studies (GWAS) have identified hundreds of loci underlying adult-onset asthma (AOA) and childhood-onset (COA). However, the causal variants, regulatory elements, effector genes at these are largely unknown. Methods We performed heritability enrichment analysis to determine relevant cell types for AOA COA, respectively. Next, we fine-mapped putative variants COA loci. To improve resolution fine-mapping, integrated ATAC-seq data in blood lung annotate candidate cis -regulatory elements (CREs). then computationally prioritized CREs risk, experimentally assessed their enhancer activity by massively parallel reporter assay (MPRA) bronchial epithelial cells (BECs) further validated a subset luciferase assays. Combining chromatin interaction expression quantitative trait loci, nominated targeted COA. Results Heritability suggested shared role immune development both while highlighting distinct contribution structural Functional fine-mapping uncovered 21 67 credible sets respectively, with only 16% between two. Notably, one-third contained multiple sets. Our CRE prioritization strategy 62 169 Over 60% showed open lineages, suggesting potential pleiotropic effects different types. Furthermore, were enriched enhancers MPRA BECs. The included many involved inflammatory responses. genes, including TNFSF4 , drug target undergoing clinical trials, supported two independent GWAS signals, indicating widespread allelic heterogeneity. Four out six selected demonstrated allele-specific properties assays Conclusions present comprehensive characterization genetics. results genetic basis highlighted complexity marked extensive pleiotropy

Language: Английский

Citations

1
Identification of shared genetic loci for asthma, allergic rhinitis, and pollinosis in East Asians DOI Creative Commons
Dong Wang, Shuai Liu, Qian Wu

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 19, 2025

Asthma, allergic rhinitis, and pollinosis are prevalent respiratory conditions that often co-occur, suggesting common genetic environmental causes. While significant progress has been made in identifying loci European populations, the architecture East Asian populations remains poorly understood. Using GWAS summary statistics from BioBank Japan, we performed multi-trait genome-wide association studies (MTAG) to quantify overlap among asthma, Asians. Genetic correlation analysis revealed positive correlations three conditions, stratified LDSC (Linkage Disequilibrium Score Regression) identified heritability enrichments Blood/Immune Digestive tissues. We discovered novel pleiotropic at 9q32 10q25.2 specific Asians, with candidate gene expression highlighting differential of AKNA, ATP6V1G1, GPAM. These findings provide new insights into shared biological mechanisms underlying these advancing our understanding their determinants potential therapeutic targets.

Language: Английский

Citations

1
Asian diversity in human immune cells DOI Creative Commons

Kian Hong Kock,

Le Min Tan,

Kyung Yeon Han

et al.

Cell, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

1
Precision Medicine—Are We There Yet? A Narrative Review of Precision Medicine’s Applicability in Primary Care DOI Open Access
William Evans, Eric M. Meslin, Joe Kai

et al.

Journal of Personalized Medicine, Journal Year: 2024, Volume and Issue: 14(4), P. 418 - 418

Published: April 15, 2024

Precision medicine (PM), also termed stratified, individualised, targeted, or personalised medicine, embraces a rapidly expanding area of research, knowledge, and practice. It brings together two emerging health technologies to deliver better individualised care: the many “-omics” arising from increased capacity understand human genome “big data” data analytics, including artificial intelligence (AI). PM has potential transform an individual’s health, moving population-based disease prevention more management. There is however tension between two, with real risk that this will exacerbate inequalities divert funds attention basic healthcare requirements leading worse outcomes for many. All areas should consider how affect their practice, now strongly encouraged supported by government initiatives research funding. In review, we discuss examples in current practice its applications primary care, such as clinical prediction tools incorporate genomic markers pharmacogenomic testing. We look towards future some key questions PM, evidence real-world impact, affordability, exacerbating inequalities, computational storage challenges applying at scale.

Language: Английский

Citations

8