ORCID Profile
0000-0001-9982-0524
Current Organisations
Icelandic Heart Association
,
University of Iceland
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Related Links
Publications
Common genetic variants associated with cognitive performance identified using the proxy-phenotype method.
Publisher: Proceedings of the National Academy of Sciences
Date: 08-09-2014
Abstract: We identify several common genetic variants associated with cognitive performance using a two-stage approach: we conduct a genome-wide association study of educational attainment to generate a set of candidates, and then we estimate the association of these variants with cognitive performance. In older Americans, we find that these variants are jointly associated with cognitive health. Bioinformatics analyses implicate a set of genes that is associated with a particular neurotransmitter pathway involved in synaptic plasticity, the main cellular mechanism for learning and memory. In addition to the substantive contribution, this work also serves to show a proxy-phenotype approach to discovering common genetic variants that is likely to be useful for many phenotypes of interest to social scientists (such as personality traits).
A novel Alzheimer disease locus located near the gene encoding tau protein
Publisher: Springer Science and Business Media LLC
Date: 17-03-2015
DOI: 10.1038/MP.2015.23
A genome-wide association study of serum proteins reveals shared loci with common diseases
Publisher: Cold Spring Harbor Laboratory
Date: 04-07-2021
DOI: 10.1101/2021.07.02.450858
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 in iduals, revealing 4,113 independent associations between genetic variants and 2,099 serum proteins, of which 37% 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.
Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals
Publisher: Springer Science and Business Media LLC
Date: 23-07-2018
Meta‐analysis on blood transcriptomic studies identifies consistently coexpressed protein–protein interaction modules as robust markers of human aging
Publisher: Wiley
Date: 19-11-2013
DOI: 10.1111/ACEL.12160
Integrated Systems Approach Identifies Genetic Nodes and Networks in Late-Onset Alzheimer’s Disease
Publisher: Elsevier BV
Date: 04-2013
Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins
Publisher: Springer Science and Business Media LLC
Date: 28-10-2014
DOI: 10.1038/NCOMMS6068
Abstract: Statins effectively lower LDL cholesterol levels in large studies and the observed interin idual response variability may be partially explained by genetic variation. Here we perform a pharmacogenetic meta-analysis of genome-wide association studies (GWAS) in studies addressing the LDL cholesterol response to statins, including up to 18,596 statin-treated subjects. We validate the most promising signals in a further 22,318 statin recipients and identify two loci, SORT1/CELSR2/PSRC1 and SLCO1B1 , not previously identified in GWAS. Moreover, we confirm the previously described associations with APOE and LPA. Our findings advance the understanding of the pharmacogenetic architecture of statin response.
Coding and regulatory variants affect serum protein levels and common disease
Publisher: Cold Spring Harbor Laboratory
Date: 08-05-2020
DOI: 10.1101/2020.05.06.080440
Abstract: Circulating proteins are prognostic for human outcomes including cancer, heart failure, brain trauma and brain amyloid plaque burden. A deep serum proteome survey recently revealed close associations of serum protein networks and common diseases. The present study reveals unprecedented number of in idual serum proteins that overlap genetic signatures of diseases emanating from different tissues of the body. Here, 54,469 low-frequency and common exome-array variants were compared with 4782 protein measurements in the serum of 5343 in iduals of the deeply annotated AGES Reykjavik cohort. Using a study-wide significant threshold, 2019 independent exome array variants affecting levels of 2135 serum proteins were identified. These variants overlapped genetic loci for hundreds of complex disease traits, emphasizing the emerging role for serum proteins as biomarkers of and potential causative agents of multiple diseases.
The Association of a SNP Upstream of INSIG2 with Body Mass Index is Reproduced in Several but Not All Cohorts
Publisher: Public Library of Science (PLoS)
Date: 27-04-2007
A Meta-analysis of Gene Expression Signatures of Blood Pressure and Hypertension
Publisher: Public Library of Science (PLoS)
Date: 18-03-2015
Antihypertensive medication uses and serum ACE2 levels
Publisher: Cold Spring Harbor Laboratory
Date: 25-05-2020
DOI: 10.1101/2020.05.21.20108738
Abstract: 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. To examine the effect of ACEIs or ARBs treatment on serum levels of ACE2 and other key enzymes in the renin-angiotensin system (RAS). 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. The AGES-RS study population was stratified by ACEIs and ARBs medication use and compared for age, body mass index (BMI) (kg/m 2 ), hypertension and type 2 diabetes (T2D) as well as serum levels of renin, ACE and ACE2. While renin and ACE levels were significantly raised in serum of in iduals on ACEIs or ARBs treatments, the ACE2 levels remained unaffected. 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. Does treatment with the antihypertensive medications angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) result in elevated levels of the cellular receptor for the coronavirus SARS-CoV-2, ACE2? In a single center population-based cohort (AGES-RS), 699 and 753 in iduals were either on ACEIs or ARBs treatment, respectively. The serum levels of the key enzymes in the renin-angiotensin system (RAS), renin, ACE and ACE2 were measured in 5457 subjects of the AGES-RS and their serum levels in in iduals on ACEIs or ARBs treatment compared to those not using these medications. While renin and ACE were significantly raised in serum of ACEIs and ARBs users, the levels of ACE2 remained unaffected. These results do not support the proposed routine discontinuation of ACEIs or ARBs among patients affected with COVID-19.
A genome-wide association study of serum proteins reveals shared loci with common diseases
Publisher: Springer Science and Business Media LLC
Date: 25-01-2022
DOI: 10.1038/S41467-021-27850-Z
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 in iduals, 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.
Molecular screening of familial hypercholesterolemia in Icelanders
Publisher: Informa UK Limited
Date: 24-07-2020
Convergent genetic and expression data implicate immunity in Alzheimer's disease
Publisher: Wiley
Date: 19-12-2014
The Effects of the β3-Adrenoceptor Agonist BRL 35135 on UCP Isoform mRNA Expression
Publisher: Elsevier BV
Date: 11-1998
Abstract: The mitochondrial uncoupling protein UCP-1 uncouples respiration from ATP synthesis in brown adipose tissue (BAT) and thus energy is dissipated as heat. Recently two further isoforms have been identified which may play a similar role in other tissues. We have determined the effects of the rodent-selective beta3-adrenoceptor (beta3-AR) agonist BRL 35135, on beta3-AR and UCP mRNA levels in tissues from lean and obese (fa/fa) Zucker rats. beta3-AR mRNA levels were reduced in fa/fa white (WAT) and brown (BAT) adipose tissue relative to levels in lean littermates. BRL 35135 treatment increased expression levels of beta3-AR mRNA in both genotypes. UCP-2 and UCP-3 mRNA levels in BAT, WAT and skeletal muscle were reduced by 2-3 fold in the fa/fa rats relative to the lean rats. We confirm that BRL 35135 increases BAT UCP-1 mRNA in lean rats, and find that BAT UCP-3 mRNA was reduced 3.2 fold, with no changes in UCP-2 expression. In WAT BRL 35135 increased UCP-2 and UCP-3 expression 2-3 fold in both lean and fa/fa rats. In lean rats, skeletal muscle UCP-3 mRNA was increased 2.3 fold by BRL 35135 whereas UCP-2 was reduced by 2.2 fold. BRL 35135 had no effects on UCP-2 and UCP-3 expression in skeletal muscle of the fa/fa rats. Our results demonstrate that mechanisms regulating UCP isoform synthesis in fa/fa rats are impaired and that WAT could be involved in the thermogenic response of BRL 35135.
Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization
Publisher: Springer Science and Business Media LLC
Date: 22-06-2014
DOI: 10.1038/NG.3014
Co-regulatory networks of human serum proteins link genetics to disease
Publisher: American Association for the Advancement of Science (AAAS)
Date: 24-08-2018
Abstract: Understanding the function of human blood serum proteins in disease has been limited by difficulties in monitoring their production, accumulation, and distribution. Emilsson et al. investigated human serum proteins of more than 5000 Icelanders over the age of 65. The composition of blood serum includes a complex regulatory network of proteins that are globally coordinated across most or all tissues. The authors identified modules and functional groups associated with disease and health outcomes and were able to link genetic variants to complex diseases. Science , this issue p. 769
Genetic variants linked to education predict longevity
Publisher: Proceedings of the National Academy of Sciences
Date: 31-10-2016
Abstract: In iduals with more education tend to live longer. Genetic variants have been discovered that predict educational attainment. We tested whether a “polygenic score” based on these genetic variants could make predictions about people’s lifespan. We used data from three cohort studies (including ,000 participants) to examine the link between offspring polygenic score for education and parental longevity. Across the studies, we found that participants with more education-linked genetic variants had longer-living parents compared with those with the lowest genetic education scores, those with the highest scores had parents who lived on average 6 months longer. This finding suggests the hypothesis that part of the ultimate explanation for the extended longevity of better-educated people is an underlying, quantifiable, genetic propensity.
Circulating Protein Signatures and Causal Candidates for Type 2 Diabetes
Publisher: American Diabetes Association
Date: 08-05-2020
DOI: 10.2337/DB19-1070
Abstract: The increasing prevalence of type 2 diabetes poses a major challenge to societies worldwide. Blood-based factors like serum proteins are in contact with every organ in the body to mediate global homeostasis and may thus directly regulate complex processes such as aging and the development of common chronic diseases. We applied a data-driven proteomics approach, measuring serum levels of 4,137 proteins in 5,438 elderly Icelanders, and identified 536 proteins associated with prevalent and/or incident type 2 diabetes. We validated a subset of the observed associations in an independent case-control study of type 2 diabetes. These protein associations provide novel biological insights into the molecular mechanisms that are dysregulated prior to and following the onset of type 2 diabetes and can be detected in serum. A bidirectional two-s le Mendelian randomization analysis indicated that serum changes of at least 23 proteins are downstream of the disease or its genetic liability, while 15 proteins were supported as having a causal role in type 2 diabetes.
On the Replication of Genetic Associations: Timing Can Be Everything!
Publisher: Elsevier BV
Date: 04-2008
Genome-wide association study identifies 74 loci associated with educational attainment.
Publisher: Springer Science and Business Media LLC
Date: 11-05-2016
DOI: 10.1038/NATURE17671
Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes
Publisher: Springer Science and Business Media LLC
Date: 15-01-2006
DOI: 10.1038/NG1732
Abstract: We have previously reported suggestive linkage of type 2 diabetes mellitus to chromosome 10q. We genotyped 228 microsatellite markers in Icelandic in iduals with type 2 diabetes and controls throughout a 10.5-Mb interval on 10q. A microsatellite, DG10S478, within intron 3 of the transcription factor 7-like 2 gene (TCF7L2 formerly TCF4) was associated with type 2 diabetes (P = 2.1 x 10(-9)). This was replicated in a Danish cohort (P = 4.8 x 10(-3)) and in a US cohort (P = 3.3 x 10(-9)). Compared with non-carriers, heterozygous and homozygous carriers of the at-risk alleles (38% and 7% of the population, respectively) have relative risks of 1.45 and 2.41. This corresponds to a population attributable risk of 21%. The TCF7L2 gene product is a high mobility group box-containing transcription factor previously implicated in blood glucose homeostasis. It is thought to act through regulation of proglucagon gene expression in enteroendocrine cells via the Wnt signaling pathway.
Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease
Publisher: Springer Science and Business Media LLC
Date: 17-07-2017
DOI: 10.1038/NG.3916
Co-operative financial institutions and local development in China
Publisher: Elsevier BV
Date: 06-2015
ACE2 levels are altered in comorbidities linked to severe outcome in COVID-19
Publisher: Cold Spring Harbor Laboratory
Date: 05-06-2020
DOI: 10.1101/2020.06.04.20122044
Abstract: Severity of outcome in COVID-19 is disproportionately higher among the obese, males, smokers, those suffering from hypertension, kidney disease, coronary heart disease (CHD) and/or type 2 diabetes (T2D). We examined if serum levels of ACE2, the cellular entry point for the coronavirus SARS-CoV-2, were altered in these high-risk groups. Associations of serum ACE2 levels to hypertension, T2D, obesity, CHD, smokers and males in 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). Smokers, males, and in iduals with T2D or obesity have altered serum levels of ACE2 that may influence productive infection of SARS-CoV-2 in these high-risk groups. ACE2 levels are upregulated in some patient groups with comorbidities linked to COVID-19 and as such may have an emerging role as outcome in COVID-19. a circulating biomarker for severity of severity of outcome in COVID-19. Severity of outcome in COVID-19 is disproportionately higher among the obese, males, smokers, those suffering from hypertension, kidney disease, coronary heart disease (CHD) and/or type 2 diabetes (T2D). Thus, we asked if the coronavirus SARS-CoV-2 receptor ACE2 was altered in the sera from these high-risk groups? In a single center population-based study of 5457 Icelanders, the Age, Gene/Environment Susceptibility Reykjavik Study (AGES-RS), we find that ACE2 levels are significantly elevated in serum from smokers, obese and diabetic in iduals, while reduced in males. These results demonstrate that in iduals with comorbidities associated with infection of SARS-CoV-2 in these in iduals. severe outcome in COVID-19 have altered serum levels of ACE2 that may influence productive
Genome-wide association study of sexual maturation in males and females highlights a role for body mass and menarche loci in male puberty
Publisher: Oxford University Press (OUP)
Date: 25-04-2014
DOI: 10.1093/HMG/DDU150
Large-scale plasma proteomic analysis identifies proteins and pathways associated with dementia risk
Publisher: Springer Science and Business Media LLC
Date: 14-05-2021
A variant in CDKAL1 influences insulin response and risk of type 2 diabetes
Publisher: Springer Science and Business Media LLC
Date: 26-04-2007
DOI: 10.1038/NG2043
Abstract: We conducted a genome-wide association study for type 2 diabetes (T2D) in Icelandic cases and controls, and we found that a previously described variant in the transcription factor 7-like 2 gene (TCF7L2) gene conferred the most significant risk. In addition to confirming two recently identified risk variants, we identified a variant in the CDKAL1 gene that was associated with T2D in in iduals of European ancestry (allele-specific odds ratio (OR) = 1.20 (95% confidence interval, 1.13-1.27), P = 7.7 x 10(-9)) and in iduals from Hong Kong of Han Chinese ancestry (OR = 1.25 (1.11-1.40), P = 0.00018). The genotype OR of this variant suggested that the effect was substantially stronger in homozygous carriers than in heterozygous carriers. The ORs for homozygotes were 1.50 (1.31-1.72) and 1.55 (1.23-1.95) in the European and Hong Kong groups, respectively. The insulin response for homozygotes was approximately 20% lower than for heterozygotes or noncarriers, suggesting that this variant confers risk of T2D through reduced insulin secretion.
Coding and regulatory variants are associated with serum protein levels and disease
Publisher: Springer Science and Business Media LLC
Date: 25-01-2022
DOI: 10.1038/S41467-022-28081-6
Abstract: Circulating proteins can be used to diagnose and predict disease-related outcomes. A deep serum proteome survey recently revealed close associations between serum protein networks and common disease. In the current study, 54,469 low-frequency and common exome-array variants were compared to 4782 protein measurements in the serum of 5343 in iduals from the AGES Reykjavik cohort. This analysis identifies a large number of serum proteins with genetic signatures overlapping those of many diseases. More specifically, using a study-wide significance threshold, we find that 2021 independent exome array variants are associated with serum levels of 1942 proteins. These variants reside in genetic loci shared by hundreds of complex disease traits, highlighting serum proteins’ emerging role as biomarkers and potential causative agents of a wide range of diseases.
A proteogenomic signature of age-related macular degeneration in blood
Publisher: Springer Science and Business Media LLC
Date: 13-06-2022
DOI: 10.1038/S41467-022-31085-X
Abstract: Age-related macular degeneration (AMD) is one of the most common causes of visual impairment in the elderly, with a complex and still poorly understood etiology. Whole-genome association studies have discovered 34 genomic regions associated with AMD. However, the genes and cognate proteins that mediate the risk, are largely unknown. In the current study, we integrate levels of 4782 human serum proteins with all genetic risk loci for AMD in a large population-based study of the elderly, revealing many proteins and pathways linked to the disease. Serum proteins are also found to reflect AMD severity independent of genetics and predict progression from early to advanced AMD after five years in this population. A two-s le Mendelian randomization study identifies several proteins that are causally related to the disease and are directionally consistent with the observational estimates. In this work, we present a robust and unique framework for elucidating the pathobiology of AMD.
Erratum: Common genetic variants associated with cognitive performance identified using the proxy-phenotype method (Proc Natl Acad Sci USA (2014) 111 (13790-13794) DOI: 10.1073/pnas.1404623111)
Publisher: Proceedings of the National Academy of Sciences
Date: 08-01-2015
Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences
Publisher: Springer Science and Business Media LLC
Date: 14-01-2019
A Proteogenomic Signature of Age-related Macular Degeneration in Blood
Publisher: Cold Spring Harbor Laboratory
Date: 30-07-2021
DOI: 10.1101/2021.07.27.21261194
Abstract: Age-related macular degeneration (AMD) is one of the most frequent causes of visual impairment in the elderly population. The overall etiology of AMD is complex and still poorly understood, though age, obesity, smoking, and high-density lipoprotein are known risk factors. In one of the first successful reported genome-wide association studies (GWAS), common genetic variants were strongly associated with AMD, including variants within the complement factor H (CFH) gene. To date, 34 genomic regions have been linked to AMD however, the genes that mediate the risk remain largely unknown, indicating that novel approaches to identifying causal candidates are needed. Recent advances in proteomic technology have exposed the serum proteome’s depth and complexity. In the Age, Gene/Environment Susceptibility Reykjavik Study (AGES-RS), a broad population-based study of the elderly (N = 5764), levels of 4137 human serum proteins and associated networks were integrated with established genetic risk loci for AMD, revealing many predicted as well as novel proteins and pathways, linked to the disease. Serum proteins were also found to reflect AMD severity independent of genetics and predict progression from early to advanced AMD after five years in this population. A two-s le Mendelian randomization study of five proteins associated with AMD found CFHR1, CFHR5, and FUT5 to be causally related to the disease, all of which were directionally consistent with the observational estimates. This study provides a robust and unique framework for elucidating the pathobiology of AMD.
Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility
Publisher: Springer Science and Business Media LLC
Date: 09-02-2014
DOI: 10.1038/NG.2897
Genetic studies of body mass index yield new insights for obesity biology
Publisher: Springer Science and Business Media LLC
Date: 11-02-2015
DOI: 10.1038/NATURE14177
Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies
Publisher: Springer Science and Business Media LLC
Date: 21-11-2010
DOI: 10.1038/NG.714
Polygenic prediction of educational attainment within and between families from genome-wide association analyses in 3 million individuals
Publisher: Springer Science and Business Media LLC
Date: 31-03-2022
DOI: 10.1038/S41588-022-01016-Z
Abstract: We conduct a genome-wide association study (GWAS) of educational attainment (EA) in a s le of ~3 million in iduals and identify 3,952 approximately uncorrelated genome-wide-significant single-nucleotide polymorphisms (SNPs). A genome-wide polygenic predictor, or polygenic index (PGI), explains 12–16% of EA variance and contributes to risk prediction for ten diseases. Direct effects (i.e., controlling for parental PGIs) explain roughly half the PGI’s magnitude of association with EA and other phenotypes. The correlation between mate-pair PGIs is far too large to be consistent with phenotypic assortment alone, implying additional assortment on PGI-associated factors. In an additional GWAS of dominance deviations from the additive model, we identify no genome-wide-significant SNPs, and a separate X-chromosome additive GWAS identifies 57.
New genetic loci link adipose and insulin biology to body fat distribution
Publisher: Springer Science and Business Media LLC
Date: 11-02-2015
DOI: 10.1038/NATURE14132
Related Organisations
Related Funding Activities
No related grants have been discovered for Valur Emilsson.