Biology subjects

Emilsson, V.

Publications and source records attributed to Emilsson, V..

6 recordsLinked to original sources

bioRxiv2026

The impact of low-frequency genetic variants on serum protein levels

The mapping of protein quantitative trait loci (pQTLs) can provide molecular links between genotype and phenotype. Most such studies focus on common variants, but the effects of low-frequency (LF) variants remain underexplored. Focusing on cis-pQTLs, we integrated serum measurements of 7,596 proteins with genomic data, including LF variants (minor allele frequency [MAF] 0.1-1%), in 5,291 Icelanders to identify independent cis-pQTLs for 2,166 SOMAmers. Incorporating LF variants increased the number of detected genetic signals per protein, demonstrating widespread allelic heterogeneity in cis-acting regulation of serum proteins. LF pQTLs were enriched for coding variants in the respective protein-encoding gene, but also among distal secondary signals, revealing additional regulatory layers not captured by common variants alone. Proteins affected by common variant cis-pQTLs were more often secreted and exhibited tissue-specific expression, whereas proteins exclusively affected by LF variants were primarily from more constrained and biologically essential pathways. Expanding both protein coverage and the allele-frequency spectrum reveals a more complex and heterogeneous cis-regulatory architecture of circulating proteins.

genomics↗

bioRxiv2025

Long-term temporal stability of circulating proteins in older adults

Circulating proteins reflect diverse biological processes and can offer critical insights into an individual s overall health and aging trajectory. The circulating proteome is shaped by a complex interplay of genetic, biological, and environmental factors across the lifespan. However, little is known about which factors influence its long-term temporal stability. Here we used SomaScan proteomics to evaluate the five-year temporal stability of 7,288 proteins measured in serum from 3,093 participants (mean age 76 years) of the Age, Gene/Environment Susceptibility (AGES)-Reykjavik study. We observed a wide variability in the temporal stability of individual proteins, with temporally stable proteins more often being extracellular and associated with diseases, while temporally variable proteins are typically involved in intracellular housekeeping functions. We demonstrate that temporal stability of circulating proteins does not reflect that of transcriptomic stability in tissues, and that genetic effects and disease stage are two major contributors to protein temporal stability in the circulation. Our findings underscore the protein-specific differences in long-term temporal stability, and the genetic and biological factors influencing them, which are particularly important to consider in the context of biomarker development and precision medicine.

genomics↗

bioRxiv2021

A genome-wide association study of serum proteins reveals shared loci with common diseases

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 4,113 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 proteins 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.

genomics↗

bioRxiv2020

Human serum proteome profoundly overlaps with genetic signatures of disease

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 individual 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 individuals 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.

genetics↗

bioRxiv2019

Deep serum proteomics reveal biomarkers and causal candidates for type 2 diabetes

The prevalence of type 2 diabetes mellitus (T2DM) is expected to increase rapidly in the next decades, posing a major challenge to societies worldwide. The emerging era of precision medicine calls for the discovery of biomarkers of clinical value for prediction of disease onset, where causal biomarkers can furthermore provide actionable targets. 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 Icelanders to discover novel biomarkers for incident T2DM and describe the serum protein profile of prevalent T2DM. We identified 536 proteins associated with incident or prevalent T2DM. Through LASSO penalized logistic regression analysis combined with bootstrap resampling, a panel of 20 protein biomarkers that accurately predicted incident T2DM was identified with a significant incremental improvement over traditional risk factors. Finally, a Mendelian randomization analysis provided support for a causal role of 48 proteins in the development of T2DM, which could be of particular interest as novel therapeutic targets.

genetics↗

bioRxiv2018

Molecular Screening of Familial Hypercholesterolemia in the Icelandic Population

Familial hypercholesterolemia (FH) is a monogenic disease characterized by a lifelong exposure to high LDL-C levels that can lead to early onset coronary heart disease (CHD). The main causes of FH identified to date include loss-of-function mutations in LDLR or APOB, or gain-of-function mutations in PCSK9. Early diagnosis and genetic testing of FH suspects is critical for improved prognosis of affected individuals as lipid lowering treatments are effective in preventing CHD related morbidity and mortality. In the present manuscript, we developed a comprehensive next generation sequencing (NGS) panel which we applied on two different resources of FH in the Icelandic population: 62 subjects from 23 FH families with known or unknown culprit mutations, and a population-based sampling of 315 subjects selected for total cholesterol levels above the 95th percentile cut-point. The application of the NGS panel revealed significant diagnostic yields in identifying pathogenic LDLR mutations in both family and population-based genetic testing.

genetics↗