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

Single-cell analysis of human diversity in circulating immune cells DOI
Kian Hong Kock, Le Min Tan,

Kyung Yeon Han

et al.

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

Published: July 1, 2024

Summary Lack of diversity and proportionate representation in genomics datasets databases contributes to inequity healthcare outcomes globally 1,2 . The relationships human with biological biomedical phenotypes are pervasive 3 , yet remain understudied, particularly a single-cell context. Here we present the Asian Immune Diversity Atlas (AIDA), multi-national RNA-sequencing (scRNA-seq) healthy reference atlas immune cells. AIDA comprises 1,265,624 circulating cells from 619 donors 6 controls, spanning 7 population groups across 5 countries. is one largest blood terms number cells, also most diverse groups. Though frequently compared at continental level, identified impact sub-continental on cellular molecular properties These included cell populations genes implicated disease risk pathogenesis as well those relevant for diagnostics. We detected signatures not apparent level types, modulation effects age sex by self-reported ethnicity. discovered functional genetic variants influencing type-specific gene expression, including context-dependent effects, which were under-represented analyses non-Asian groups, helped contextualise disease-associated variants. validated our findings using multiple independent cohorts. provides fundamental insights into phenotypes, enables multi-ancestry datasets, facilitates development precision medicine efforts Asia beyond.

Language: Английский

Citations

7
Epigenomic partitioning of a polygenic risk score for asthma reveals distinct genetically driven disease pathways DOI Creative Commons
Bernard Stikker, Lianne Trap, Bahareh Sedaghati-khayat

et al.

European Respiratory Journal, Journal Year: 2024, Volume and Issue: 64(2), P. 2302059 - 2302059

Published: June 20, 2024

Individual differences in susceptibility to developing asthma, a heterogeneous chronic inflammatory lung disease, are poorly understood. Whether genetics can predict asthma risk and how genetic variants modulate the complex pathophysiology of still debated.

Language: Английский

Citations

6
Prioritization of genes for translation: a computational approach DOI
Simone C. da Silva Rosa, Amir Barzegar Behrooz, Sofia Guedes

et al.

Expert Review of Proteomics, Journal Year: 2024, Volume and Issue: 21(4), P. 125 - 147

Published: April 2, 2024

Introduction Gene identification for genetic diseases is critical the development of new diagnostic approaches and personalized treatment options. Prioritization gene translation an important consideration in molecular biology field, allowing researchers to focus on most promising candidates further investigation.

Language: Английский

Citations

5
To weight or not to weight? The effect of selection bias in 3 large electronic health record-linked biobanks and recommendations for practice DOI
Maxwell Salvatore, Ritoban Kundu, Xu Shi

et al.

Journal of the American Medical Informatics Association, Journal Year: 2024, Volume and Issue: 31(7), P. 1479 - 1492

Published: May 14, 2024

To develop recommendations regarding the use of weights to reduce selection bias for commonly performed analyses using electronic health record (EHR)-linked biobank data.

Language: Английский

Citations

5
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

Citations

5