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Book ; Thesis: Transfer RNA regulation and bacterial growth

Emilsson, Valur

(Comprehensive summaries of Uppsala dissertations from the Faculty of Science ; 422 ; Acta Universitatis Upsaliensis)

1993

Author's details	by Valur Emilsson
Series title	Comprehensive summaries of Uppsala dissertations from the Faculty of Science ; 422 Acta Universitatis Upsaliensis
Collection
Language	English
Size	54 S.
Publisher	Almqvist & Wiksell
Publishing place	Stockholm
Publishing country	Sweden
Document type	Book ; Thesis
Thesis / German Habilitation thesis	Uppsala, Univ., Diss., 1993
HBZ-ID	HT007594695
ISBN	91-554-3046-5 ; 978-91-554-3046-7
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Article ; Online: Proteomic associations with forced expiratory volume: a Mendelian randomisation study.

Axelsson, Gisli Thor / Jonmundsson, Thorarinn / Woo, Youngjae / Frick, Elisabet Alexandra / Aspelund, Thor / Loureiro, Joseph J / Orth, Anthony P / Jennings, Lori L / Gudmundsson, Gunnar / Emilsson, Valur / Gudmundsdottir, Valborg / Gudnason, Vilmundur

Respiratory research

2024 Volume 25, Issue 1, Page(s) 44

Abstract: Background: A decline in forced expiratory volume (FEV1) is a hallmark of respiratory diseases that are an important cause of morbidity among the elderly. While some data exist on biomarkers that are related to FEV1, we sought to do a systematic ... ...

Abstract	Background: A decline in forced expiratory volume (FEV1) is a hallmark of respiratory diseases that are an important cause of morbidity among the elderly. While some data exist on biomarkers that are related to FEV1, we sought to do a systematic analysis of causal relations of biomarkers with FEV1. Methods: Data from the population-based AGES-Reykjavik study were used. Serum proteomic measurements were done using 4782 DNA aptamers (SOMAmers). Data from 1479 participants with spirometric data were used to assess the association of SOMAmer measurements with FEV1 using linear regression. Bi-directional two-sample Mendelian randomisation (MR) analyses were done to assess causal relations of observationally associated SOMAmers with FEV1, using genotype and SOMAmer data from 5368 AGES-Reykjavik participants and genetic associations with FEV1 from a publicly available GWAS (n = 400,102). Results: In observational analyses, 530 SOMAmers were associated with FEV1 after multiple testing adjustment (FDR < 0.05). The most significant were Retinoic Acid Receptor Responder 2 (RARRES2), R-Spondin 4 (RSPO4) and Alkaline Phosphatase, Placental Like 2 (ALPPL2). Of the 257 SOMAmers with genetic instruments available, eight were associated with FEV1 in MR analyses. Three were directionally consistent with the observational estimate, Thrombospondin 2 (THBS2), Endoplasmic Reticulum Oxidoreductase 1 Beta (ERO1B) and Apolipoprotein M (APOM). THBS2 was further supported by a colocalization analysis. Analyses in the reverse direction, testing whether changes in SOMAmer levels were caused by changes in FEV1, were performed but no significant associations were found after multiple testing adjustments. Conclusions: In summary, this large scale proteogenomic analyses of FEV1 reveals circulating protein markers of FEV1, as well as several proteins with potential causality to lung function.
MeSH term(s)	Humans ; Female ; Pregnancy ; Aged ; Forced Expiratory Volume/genetics ; Lung ; Proteomics ; Placenta ; Biomarkers
Chemical Substances	Biomarkers
Language	English
Publishing date	2024-01-18
Publishing country	England
Document type	Journal Article
ZDB-ID	2041675-1
ISSN	1465-993X ; 1465-993X
ISSN (online)	1465-993X
ISSN	1465-993X
DOI	10.1186/s12931-023-02587-z
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Article ; Online: Predicting health and life span with the deep plasma proteome.

Emilsson, Valur / Gudnason, Vilmundur / Jennings, Lori L

Nature medicine

2019 Volume 25, Issue 12, Page(s) 1815–1816

MeSH term(s)	Aging/blood ; Aging/genetics ; Humans ; Longevity/genetics ; Proteome/genetics
Chemical Substances	Proteome
Language	English
Publishing date	2019-12-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	1220066-9
ISSN	1546-170X ; 1078-8956
ISSN (online)	1546-170X
ISSN	1078-8956
DOI	10.1038/s41591-019-0677-y
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Zs.A 4212: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: It's in Our Blood: A Glimpse of Personalized Medicine.

Lamb, John R / Jennings, Lori L / Gudmundsdottir, Valborg / Gudnason, Vilmundur / Emilsson, Valur

Trends in molecular medicine

2020 Volume 27, Issue 1, Page(s) 20–30

Abstract: Recent advances in protein profiling technology has facilitated simultaneous measurement of thousands of proteins in large population studies, exposing the depth and complexity of the plasma and serum proteomes. This revealed that proteins in circulation ...

Abstract	Recent advances in protein profiling technology has facilitated simultaneous measurement of thousands of proteins in large population studies, exposing the depth and complexity of the plasma and serum proteomes. This revealed that proteins in circulation were organized into regulatory modules under genetic control and closely associated with current and future common diseases. Unlike networks in solid tissues, serum protein networks comprise members synthesized across different tissues of the body. Genetic analysis reveals that this cross-tissue regulation of the serum proteome participates in systemic homeostasis and mirrors the global disease state of individuals. Here, we discuss how application of this information in routine clinical evaluations may transform the future practice of medicine.
MeSH term(s)	Blood Proteins/metabolism ; Disease Susceptibility ; Genomics/methods ; Humans ; Organ Specificity ; Precision Medicine/methods ; Proteome ; Proteomics/methods
Chemical Substances	Blood Proteins ; Proteome
Language	English
Publishing date	2020-09-25
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2036490-8
ISSN	1471-499X ; 1471-4914
ISSN (online)	1471-499X
ISSN	1471-4914
DOI	10.1016/j.molmed.2020.09.003
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Article ; Online: Characterization of Genetic Networks Associated with Alzheimer's Disease.

Zhang, Bin / Tran, Linh / Emilsson, Valur / Zhu, Jun

Methods in molecular biology (Clifton, N.J.)

2016 Volume 1303, Page(s) 459–477

Abstract: At the molecular level, the genetics of complex disease such as Alzheimer's disease (AD) manifests itself as series of alterations in the molecular interactions in pathways and networks that define biological processes underlying the pathophysiological ... ...

Abstract	At the molecular level, the genetics of complex disease such as Alzheimer's disease (AD) manifests itself as series of alterations in the molecular interactions in pathways and networks that define biological processes underlying the pathophysiological states of disease. While large-scale genome-wide association (GWA) studies of late-onset alzheimer's disease (LOAD) have uncovered prominent genomic regions linked to the disease, the cause for the vast majority of LOAD cases still remains unknown. Increasingly available large-scale genomic and genetic data related to LOAD has made it possible to comprehensively uncover the mechanisms causally lined to LOAD in a completely data-driven manner. Here we review the various aspects of systems/network biology approaches and methodology in constructing genetic networks associated with AD from large sampling of postmortem brain tissues. We describe in detail a multiscale network modeling approach (MNMA) that integrates interaction and causal gene networks to analyze large-scale DNA, gene expression and pathophysiological data from multiple post-mortem brain regions of LOAD patients as well non-demented normal controls. MNMA first employs weighted gene co-expression network analysis (WGCNA) to construct multi-tissue networks that simultaneously capture intra-tissue and inter-tissue gene-gene interactions and then quantifies the change in connectivity among highly co-expressed genes in LOAD with respect to the normal state. Co-expressed gene modules are then rank ordered by relevance to pathophysiological traits and enrichment of genes differentially expressed in LOAD. Causal regulatory relationships among the genes in each module are then determined by a Bayesian network inference framework that is used to formally integrate genetic and gene expression information. MNMA has uncovered a massive remodeling of network structures in LOAD and identified novel subnetworks and key regulators that are causally linked to LOAD. In the end, we will outline the challenges in systems/network approaches to LOAD.
MeSH term(s)	Alzheimer Disease/genetics ; Bayes Theorem ; Gene Regulatory Networks ; Humans ; Systems Biology/methods
Language	English
Publishing date	2016
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-4939-2627-5_28
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Serum proteomics reveals APOE dependent and independent protein signatures in Alzheimer's disease.

Gudmundsdottir, Valborg / Frick, Elisabet / Emilsson, Valur / Jonmundsson, Thorarinn / Steindorsdottir, Anna / Johnson, Erik C B / Puerta, Raquel / Dammer, Eric / Shantaraman, Anantharaman / Cano, Amanda / Boada, Merce / Valero, Sergi / Garcia-Gonzalez, Pablo / Gudmundsson, Elias / Gudjonsson, Alexander / Pitts, Rebecca / Qiu, Xiazi / Finkel, Nancy / Loureiro, Joseph /

Orth, Anthony / Seyfried, Nicholas / Levey, Allan / Ruiz, Agustín / Aspelund, Thor / Jennings, Lori / Launer, Lenore / Gudnason, Vilmundur

Research square

2024

Abstract: The current demand for early intervention, prevention, and treatment of late onset Alzheimer's disease (LOAD) warrants deeper understanding of the underlying molecular processes which could contribute to biomarker and drug target discovery. Utilizing ... ...

Abstract	The current demand for early intervention, prevention, and treatment of late onset Alzheimer's disease (LOAD) warrants deeper understanding of the underlying molecular processes which could contribute to biomarker and drug target discovery. Utilizing high-throughput proteomic measurements in serum from a prospective population-based cohort of older adults (n = 5,294), we identified 303 unique proteins associated with incident LOAD (median follow-up 12.8 years). Over 40% of these proteins were associated with LOAD
Language	English
Publishing date	2024-01-09
Publishing country	United States
Document type	Preprint
DOI	10.21203/rs.3.rs-3706206/v1
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Article: Serum levels of ACE2 are higher in patients with obesity and diabetes

Emilsson, Valur / Gudmundsson, Elias F. / Aspelund, Thor / Jonsson, Brynjolfur G. / Gudjonsson, Alexander / Launer, Lenore J. / Lamb, John R. / Gudmundsdottir, Valborg / Jennings, Lori L. / Gudnason, Vilmundur

Obesity science & practice. 2021 Apr., v. 7, no. 2

2021

Abstract: OBJECTIVE: As severity of outcome in COVID‐19 is disproportionately higher among individuals with obesity, smokers, patients with hypertension, kidney disease, chronic pulmonary disease, coronary heart disease (CHD), and/or type 2 diabetes (T2D), serum ... ...

Abstract	OBJECTIVE: As severity of outcome in COVID‐19 is disproportionately higher among individuals with obesity, smokers, patients with hypertension, kidney disease, chronic pulmonary disease, coronary heart disease (CHD), and/or type 2 diabetes (T2D), serum levels of ACE2, the cellular entry point for the coronavirus SARS‐CoV‐2, were examined in these high‐risk groups. METHODS: Associations of ACE2 levels to smokers and patients with hypertension, T2D, obesity, CHD, or COPD were investigated in a single center population‐based study of 5457 Icelanders from the Age, Gene/Environment Susceptibility Reykjavík Study (AGES‐RS) of the elderly (mean age 75 ± 6 years), using multiple linear regression analysis. RESULTS: Serum levels of ACE2 were higher in smokers and individuals with T2D and/or obesity while they were unaffected in the other patient groups. CONCLUSION: ACE2 levels are higher in some patient groups with comorbidities linked to COVID‐19 including obesity and T2D and as such may have an emerging role as a circulating biomarker for severity of outcome in the disease.
Keywords	COVID-19 infection ; Severe acute respiratory syndrome coronavirus 2 ; biomarkers ; blood serum ; coronary disease ; elderly ; genes ; hypertension ; kidney diseases ; noninsulin-dependent diabetes mellitus ; obesity ; patients ; regression analysis ; respiratory tract diseases
Language	English
Dates of publication	2021-04
Size	p. 239-243.
Publishing place	John Wiley & Sons, Ltd
Document type	Article
Note	JOURNAL ARTICLE
ZDB-ID	2836381-4
ISSN	2055-2238
ISSN	2055-2238
DOI	10.1002/osp4.472
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: A proteomic analysis of atrial fibrillation in a prospective longitudinal cohort (AGES-Reykjavik study).

Jonmundsson, Thorarinn / Steindorsdottir, Anna E / Austin, Thomas R / Frick, Elisabet A / Axelsson, Gisli T / Launer, Lenore / Psaty, Bruce M / Loureiro, Joseph / Orth, Anthony P / Aspelund, Thor / Emilsson, Valur / Floyd, James S / Jennings, Lori / Gudnason, Vilmundur / Gudmundsdottir, Valborg

Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology

2023 Volume 25, Issue 11

Abstract: Aims: Atrial fibrillation (AF) is associated with high risk of comorbidities and mortality. Our aim was to examine causal and predictive relationships between 4137 serum proteins and incident AF in the prospective population-based Age, Gene/Environment ... ...

Abstract	Aims: Atrial fibrillation (AF) is associated with high risk of comorbidities and mortality. Our aim was to examine causal and predictive relationships between 4137 serum proteins and incident AF in the prospective population-based Age, Gene/Environment Susceptibility-Reykjavik (AGES-Reykjavik) study. Methods and results: The study included 4765 participants, of whom 1172 developed AF. Cox proportional hazards regression models were fitted for 4137 baseline protein measurements adjusting for known risk factors. Protein associations were tested for replication in the Cardiovascular Health Study (CHS). Causal relationships were examined in a bidirectional, two-sample Mendelian randomization analysis. The time-dependent area under the receiver operating characteristic curve (AUC)-statistic was examined as protein levels and an AF-polygenic risk score (PRS) were added to clinical risk models. The proteomic signature of incident AF consisted of 76 proteins, of which 63 (83%) were novel and 29 (38%) were replicated in CHS. The signature included both N-terminal prohormone of brain natriuretic peptide (NT-proBNP)-dependent (e.g. CHST15, ATP1B1, and SVEP1) and independent components (e.g. ASPN, AKR1B, and LAMA1/LAMB1/LAMC1). Nine causal candidates were identified (TAGLN, WARS, CHST15, CHMP3, COL15A1, DUSP13, MANBA, QSOX2, and SRL). The reverse causal analysis suggested that most AF-associated proteins were affected by the genetic liability to AF. N-terminal prohormone of brain natriuretic peptide improved the prediction of incident AF events close to baseline with further improvements gained by the AF-PRS at all time points. Conclusion: The AF proteomic signature includes biologically relevant proteins, some of which may be causal. It mainly reflects an NT-proBNP-dependent consequence of the genetic liability to AF. N-terminal prohormone of brain natriuretic peptide is a promising marker for incident AF in the short term, but risk assessment incorporating a PRS may improve long-term risk assessment.
MeSH term(s)	Humans ; Atrial Fibrillation/diagnosis ; Atrial Fibrillation/epidemiology ; Natriuretic Peptide, Brain ; Biomarkers ; Prognosis ; Prospective Studies ; Proteomics ; Risk Factors ; Peptide Fragments ; Oxidoreductases Acting on Sulfur Group Donors ; Endosomal Sorting Complexes Required for Transport
Chemical Substances	Natriuretic Peptide, Brain (114471-18-0) ; Biomarkers ; Peptide Fragments ; QSOX2 protein, human (EC 1.8.3.2) ; Oxidoreductases Acting on Sulfur Group Donors (EC 1.8.-) ; CHMP3 protein, human ; Endosomal Sorting Complexes Required for Transport
Language	English
Publishing date	2023-11-10
Publishing country	England
Document type	Journal Article
ZDB-ID	1449879-0
ISSN	1532-2092 ; 1099-5129
ISSN (online)	1532-2092
ISSN	1099-5129
DOI	10.1093/europace/euad320
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Article ; Online: A genome-wide association study of serum proteins reveals shared loci with common diseases.

Gudjonsson, Alexander / Gudmundsdottir, Valborg / Axelsson, Gisli T / Gudmundsson, Elias F / Jonsson, Brynjolfur G / Launer, Lenore J / Lamb, John R / Jennings, Lori L / Aspelund, Thor / Emilsson, Valur / Gudnason, Vilmundur

Nature communications

2022 Volume 13, Issue 1, Page(s) 480

Abstract: With the growing number of genetic association studies, the genotype-phenotype atlas has become increasingly more complex, yet the functional consequences of most disease associated alleles is not understood. The measurement of protein level variation in ...

Abstract	With the growing number of genetic association studies, the genotype-phenotype atlas has become increasingly more complex, yet the functional consequences of most disease associated alleles is not understood. The measurement of protein level variation in solid tissues and biofluids integrated with genetic variants offers a path to deeper functional insights. Here we present a large-scale proteogenomic study in 5,368 individuals, revealing 4,035 independent associations between genetic variants and 2,091 serum proteins, of which 36% are previously unreported. The majority of both cis- and trans-acting genetic signals are unique for a single protein, although our results also highlight numerous highly pleiotropic genetic effects on protein levels and demonstrate that a protein's genetic association profile reflects certain characteristics of the protein, including its location in protein networks, tissue specificity and intolerance to loss of function mutations. Integrating protein measurements with deep phenotyping of the cohort, we observe substantial enrichment of phenotype associations for serum proteins regulated by established GWAS loci, and offer new insights into the interplay between genetics, serum protein levels and complex disease.
MeSH term(s)	Aged ; Aged, 80 and over ; Blood Proteins/genetics ; Cohort Studies ; Disease/classification ; Disease/genetics ; Female ; Genetic Predisposition to Disease ; Genome, Human ; Genome-Wide Association Study/methods ; Humans ; Iceland ; Male ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci
Chemical Substances	Blood Proteins
Language	English
Publishing date	2022-01-25
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-021-27850-z
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Article: Antihypertensive medication uses and serum ACE2 levels: ACEIs/ARBs treatment does not raise serum levels of ACE2.

Emilsson, Valur / Gudmundsson, Elias F / Aspelund, Thor / Jonsson, Brynjolfur G / Gudjonsson, Alexander / Launer, Lenore J / Jennings, Lori L / Gudmundsdottir, Valborg / Gudnason, Vilmundur

medRxiv : the preprint server for health sciences

2020

Abstract: Importance: Recent reports have shown that hypertension is the most common comorbidity associated with mortality in the current coronavirus disease 2019 (COVID-19). This has been related to the use of angiotensin-converting enzyme inhibitors (ACEIs) and ...

Abstract	Importance: Recent reports have shown that hypertension is the most common comorbidity associated with mortality in the current coronavirus disease 2019 (COVID-19). This has been related to the use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) as animal studies indicate that these medications increase levels of ACE2, the cellular entry point for the coronavirus SARS-CoV-2. This has prompted clinicians to recommend discontinuing ACEIs and ARBs. Objective: To examine the effect of ACEIs or ARBs treatment on serum levels of ACE2 and other key enzymes in the renin-angiotensin system (RAS). Design setting and participants: A single center population-based study of 5457 Icelanders from the Age, Gene/Environment Susceptibility Reykjavik Study (AGES-RS) of the elderly (mean age 75±6 years) stratified by ACEIs (N = 699) or ARBs (N = 753) treatment. Main outcomes and measures: The AGES-RS study population was stratified by ACEIs and ARBs medication use and compared for age, body mass index (BMI) (kg/m Results: While renin and ACE levels were significantly raised in serum of individuals on ACEIs or ARBs treatments, the ACE2 levels remained unaffected. Conclusions and relevance: Treatment with ACEIs or ARBs does not raise ACE2 levels in serum. Therefore, the present study does not support the proposed discontinuation of these medications among patients affected with COVID-19.
Keywords	covid19
Language	English
Publishing date	2020-05-25
Publishing country	United States
Document type	Preprint
DOI	10.1101/2020.05.21.20108738
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