Strengthening the reporting of observational studies in epidemiology using mendelian randomisation (STROBE-MR): explanation and elaboration

BMJ, Journal Year: 2021, Volume and Issue: unknown, P. n2233 - n2233

Published: Oct. 26, 2021

Mendelian randomisation (MR) studies allow a better understanding of the causal effects modifiable exposures on health outcomes, but published evidence is often hampered by inadequate reporting. Reporting guidelines help authors effectively communicate all critical information about what was done and found. STROBE-MR (strengthening reporting observational in epidemiology using mendelian randomisation) assists their MR research clearly transparently. Adopting should readers, reviewers, journal editors evaluate quality studies. This article explains 20 items checklist, along with meaning rationale, terms defined glossary. Examples transparent are used for each item to illustrate best practices.

Language: Английский

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Large-scale integration of the plasma proteome with genetics and disease

Nature Genetics, Journal Year: 2021, Volume and Issue: 53(12), P. 1712 - 1721

Published: Dec. 1, 2021

Language: Английский

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Mendelian Randomization: Concepts and Scope

Cold Spring Harbor Perspectives in Medicine, Journal Year: 2021, Volume and Issue: 12(1), P. a040501 - a040501

Published: Aug. 23, 2021

Mendelian randomization (MR) is a method of studying the causal effects modifiable exposures (i.e., potential risk factors) on health, social, and economic outcomes using genetic variants associated with specific interest. MR provides more robust understanding influence these because germline are randomly inherited from parents to offspring and, as result, should not be related confounding factors that exposure-outcome associations. The variant can therefore used tool link proposed factor outcome, estimate this effect less bias than conventional epidemiological approaches. We describe scope MR, highlighting range applications being made possible data sets resources become larger freely available. outline approach in detail, covering concepts, assumptions, estimation methods. cover some common misconceptions, provide strategies for overcoming violation discuss future prospects extending clinical applicability, methodological innovations, robustness, generalizability findings.

Language: Английский

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Mapping the proteo-genomic convergence of human diseases

Science, Journal Year: 2021, Volume and Issue: 374(6569)

Published: Nov. 11, 2021

Detangling gene-disease connections Many diseases are at least partially due to genetic causes that not always understood or targetable with specific treatments. To provide insight into the biology of various human as well potential leads for therapeutic development, Pietzner et al . undertook detailed, genome-wide proteogenomic mapping. The authors analyzed thousands between disease-associated mutations, proteins, and medical conditions, thereby providing a detailed map use by future researchers. They also supplied some examples in which they applied their approach contexts varied connective tissue disorders, gallstones, COVID-19 infections, sometimes even identifying single genes play roles multiple clinical scenarios. —YN

Language: Английский

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Genetics of circulating inflammatory proteins identifies drivers of immune-mediated disease risk and therapeutic targets

Nature Immunology, Journal Year: 2023, Volume and Issue: 24(9), P. 1540 - 1551

Published: Aug. 10, 2023

Circulating proteins have important functions in inflammation and a broad range of diseases. To identify genetic influences on inflammation-related proteins, we conducted genome-wide protein quantitative trait locus (pQTL) study 91 plasma measured using the Olink Target platform 14,824 participants. We identified 180 pQTLs (59 cis, 121 trans). Integration pQTL data with eQTL disease association studies provided insight into pathogenesis, implicating lymphotoxin-α multiple sclerosis. Using Mendelian randomization (MR) to assess causality etiology, both shared distinct effects specific across immune-mediated diseases, including directionally discordant CD40 risk rheumatoid arthritis versus sclerosis inflammatory bowel disease. MR implicated CXCL5 etiology ulcerative colitis (UC) show elevated gut transcript expression patients UC. These results targets existing drugs provide powerful resource facilitate future drug target prioritization.

Language: Английский

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Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation

Nature Genetics, Journal Year: 2021, Volume and Issue: 53(9), P. 1311 - 1321

Published: Sept. 1, 2021

Language: Английский

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Stroke genetics informs drug discovery and risk prediction across ancestries

Nature, Journal Year: 2022, Volume and Issue: 611(7934), P. 115 - 123

Published: Sept. 30, 2022

Previous genome-wide association studies (GWASs) of stroke - the second leading cause death worldwide were conducted predominantly in populations European ancestry1,2. Here, cross-ancestry GWAS meta-analyses 110,182 patients who have had a (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify signals for its subtypes at 89 (61 new) independent loci: 60 primary inverse-variance-weighted analyses 29 secondary meta-regression multitrait analyses. On basis internal validation an follow-up 89,084 additional cases (30% 1,013,843 87% risk loci 60% replicated (P < 0.05). Effect sizes highly correlated across ancestries. Cross-ancestry fine-mapping, silico mutagenesis analysis3, transcriptome-wide proteome-wide revealed putative causal genes (such as SH3PXD2A FURIN) variants GRK5 NOS3). Using three-pronged approach4, provide genetic evidence drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 VCAM1 possible targets, with drugs already under investigation F11 PROC. A polygenic score integrating ancestry-specific GWASs vascular-risk factor (integrative scores) strongly predicted ischaemic European, East Asian African ancestry5. Stroke scores predictive clinical factors 52,600 clinical-trial participants cardiometabolic disease. Our results insights to inform biology, reveal potential targets derive prediction tools

Language: Английский

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Guidelines for performing Mendelian randomization investigations: update for summer 2023

Wellcome Open Research, Journal Year: 2023, Volume and Issue: 4, P. 186 - 186

Published: Aug. 4, 2023

This paper provides guidelines for performing Mendelian randomization investigations. It is aimed at practitioners seeking to undertake analyses and write up their findings, journal editors reviewers assess manuscripts. The are divided into ten sections: motivation scope, data sources, choice of genetic variants, variant harmonization, primary analysis, supplementary sensitivity (one section on robust statistical methods one other approaches), extensions additional analyses, presentation, interpretation. These will be updated based feedback from the community advances in field. Updates made periodically as needed, least every 24 months.

Language: Английский

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Genetics meets proteomics: perspectives for large population-based studies

Nature Reviews Genetics, Journal Year: 2020, Volume and Issue: 22(1), P. 19 - 37

Published: Aug. 28, 2020

Language: Английский

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Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations

Cell, Journal Year: 2021, Volume and Issue: 184(18), P. 4784 - 4818.e17

Published: Aug. 26, 2021

Osteoarthritis affects over 300 million people worldwide. Here, we conduct a genome-wide association study meta-analysis across 826,690 individuals (177,517 with osteoarthritis) and identify 100 independently associated risk variants 11 osteoarthritis phenotypes, 52 of which have not been the disease before. We report thumb spine differences in genetic effects between weight-bearing non-weight-bearing joints. sex-specific early age-at-onset loci. integrate functional genomics data from primary patient tissues (including articular cartilage, subchondral bone, osteophytic cartilage) high-confidence effector genes. provide evidence for correlation phenotypes related to pain, main symptom, likely causal genes linked neuronal processes. Our results insights into key molecular players processes highlight attractive drug targets accelerate translation.

Language: Английский

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