Publications by authors named "Anders Malarstig"

Understanding the genetic basis of neuro-related proteins is essential for dissecting the molecular basis of human behavioural traits and the disease aetiology of neuropsychiatric disorders. Here the SCALLOP Consortium conducted a genome-wide association meta-analysis of over 12,000 individuals for 184 neuro-related proteins in human plasma. The analysis identified 125 cis-regulatory protein quantitative trait loci (cis-pQTL) and 164 trans-pQTL.

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  • Researchers studied proteins in the blood to understand how they relate to prostate cancer risk.
  • They found 20 proteins connected to different types of prostate cancer, including aggressive and early onset forms.
  • One protein, MSMB, was especially important because it helped tell the difference between normal tissue and cancerous tissue.
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  • * Our research uncovered 40 proteins linked to cancer risks, including PLAUR for breast cancer and CTRB1 for pancreatic cancer, while also noting possible negative side effects like hypertension from altering these proteins.
  • * We found 18 proteins that are associated with cancer risk and linked to existing drugs, plus 15 proteins not yet being studied for clinical use, enhancing our understanding of cancer causes and the implications of targeting these proteins for prevention.
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The solute carrier transporter family 6 (SLC6) is of key interest for their critical role in the transport of small amino acids or amino acid-like molecules. Their dysfunction is strongly associated with human diseases such as including schizophrenia, depression, and Parkinson's disease. Linking single point mutations to disease may support insights into the structure-function relationship of these transporters.

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Objective: Current breast cancer risk prediction scores and algorithms can potentially be further improved by including molecular markers. To this end, we studied the association of circulating plasma proteins using Proximity Extension Assay (PEA) with incident breast cancer risk.

Subjects: In this study, we included 1577 women participating in the prospective KARMA mammographic screening cohort.

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Creatine is an essential metabolite for the storage and rapid supply of energy in muscle and nerve cells. In humans, impaired metabolism, transport, and distribution of creatine throughout tissues can cause varying forms of mental disability, also known as creatine deficiency syndrome (CDS). So far, 80 mutations in the creatine transporter (SLC6A8) have been associated to CDS.

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Biomarkers for early detection of breast cancer may complement population screening approaches to enable earlier and more precise treatment. The blood proteome is an important source for biomarker discovery but so far, few proteins have been identified with breast cancer risk. Here, we measure 2929 unique proteins in plasma from 598 women selected from the Karolinska Mammography Project to explore the association between protein levels, clinical characteristics, and gene variants, and to identify proteins with a causal role in breast cancer.

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Background: Understanding the role of circulating proteins in prostate cancer risk can reveal key biological pathways and identify novel targets for cancer prevention.

Methods: We investigated the association of 2,002 genetically predicted circulating protein levels with risk of prostate cancer overall, and of aggressive and early onset disease, using -pQTL Mendelian randomization (MR) and colocalization. Findings for proteins with support from both MR, after correction for multiple-testing, and colocalization were replicated using two independent cancer GWAS, one of European and one of African ancestry.

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Circulating proteins have important functions in inflammation and a broad range of diseases. To identify genetic influences on inflammation-related proteins, we conducted a genome-wide protein quantitative trait locus (pQTL) study of 91 plasma proteins measured using the Olink Target platform in 14,824 participants. We identified 180 pQTLs (59 cis, 121 trans).

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  • Human plasma proteins are crucial as clinical biomarkers and potential drug targets, and studying their genetic variants can help us understand their abundance.
  • The study conducted a meta-analysis across nearly 23,000 individuals to identify genetic variants associated with 92 plasma proteins linked to cardiometabolic conditions, discovering 503 significant variants.
  • Notably, sex differences were observed in 23.5% of the identified variants, and further analysis suggested causal links between certain proteins and various health traits, providing insight into their roles in cardiometabolic diseases.
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  • Understanding the genetic foundation of neuro-related proteins is vital for exploring human behavior and neuropsychiatric disorders.
  • The SCALLOP Consortium analyzed genetic data from over 12,500 individuals, identifying numerous cis- and trans-regulatory loci affecting neuro-related proteins.
  • Their findings also suggest potential causal relationships between these proteins and traits like sleep, smoking, mental health, and highlight new opportunities for drug repurposing and therapeutic targets.
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The use of omic modalities to dissect the molecular underpinnings of common diseases and traits is becoming increasingly common. But multi-omic traits can be genetically predicted, which enables highly cost-effective and powerful analyses for studies that do not have multi-omics. Here we examine a large cohort (the INTERVAL study; n = 50,000 participants) with extensive multi-omic data for plasma proteomics (SomaScan, n = 3,175; Olink, n = 4,822), plasma metabolomics (Metabolon HD4, n = 8,153), serum metabolomics (Nightingale, n = 37,359) and whole-blood Illumina RNA sequencing (n = 4,136), and use machine learning to train genetic scores for 17,227 molecular traits, including 10,521 that reach Bonferroni-adjusted significance.

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Background: Fibroblast growth factor-23 (FGF-23) is associated with a range of cardiovascular and noncardiovascular diseases in conventional epidemiological studies, but substantial residual confounding may exist. Mendelian randomization approaches can help control for such confounding.

Methods: SCALLOP Consortium data of 19,195 participants were used to generate an FGF-23 genetic score.

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Population isolates such as those in Finland benefit genetic research because deleterious alleles are often concentrated on a small number of low-frequency variants (0.1% ≤ minor allele frequency < 5%). These variants survived the founding bottleneck rather than being distributed over a large number of ultrarare variants.

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Studies of the genetic regulation of cerebrospinal fluid (CSF) proteins may reveal pathways for treatment of neurological diseases. 398 proteins in CSF were measured in 1,591 participants from the BioFINDER study. Protein quantitative trait loci (pQTL) were identified as associations between genetic variants and proteins, with 176 pQTLs for 145 CSF proteins (P < 1.

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Background: We investigated the causality of IL-8 on carotid intima-media thickness (c-IMT), a measure of sub-clinical atherosclerosis.

Methods: The IMPROVE is a multicenter European study (n = 3,711). The association of plasma IL-8 with c-IMT (mm) was estimated by quantile regression.

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  • SARS-CoV-2 uses the ACE2 protein to enter human cells, making ACE2 crucial for COVID-19 infection and treatment; its levels vary significantly across different individuals but are not fully understood genetically.
  • In a large study involving over 28,000 individuals, researchers found genetic factors influencing plasma ACE2 levels and discovered 10 genetic loci linked to ACE2, explaining 30% of its heritability.
  • The study also indicated that higher ACE2 levels are causally associated with increased severity of COVID-19, hospitalization, and risk of infection, along with genetic links to vascular diseases and other complex health conditions.
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Background: Heart failure (HF) is a highly prevalent disorder for which disease mechanisms are incompletely understood. The discovery of disease-associated proteins with causal genetic evidence provides an opportunity to identify new therapeutic targets.

Methods: We investigated the observational and causal associations of 90 cardiovascular proteins, which were measured using affinity-based proteomic assays.

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Accessible risk predictors are crucial for improving the early detection and prognosis of breast cancer. Blood samples are widely available and contain proteins that provide important information about human health and disease, however, little is still known about the contribution of circulating proteins to breast cancer risk prediction. We profiled EDTA plasma samples collected before diagnosis from the Swedish KARMA breast cancer cohort to evaluate circulating proteins as molecular predictors.

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  • The study investigates the genetic factors influencing 184 proteins related to neurological disorders by analyzing data from over 2,800 individuals, aiming to better understand how these proteins are linked to diseases.
  • Researchers identified 214 genetic variants associated with 107 proteins, finding that most variants are cis-acting and revealing 114 new variants not previously documented.
  • The team used Mendelian randomization to establish causal links between specific proteins and neurological conditions, suggesting potential for repurposing existing drugs for Alzheimer’s, Parkinson’s, and schizophrenia.
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  • The HERMES consortium is focused on understanding the genomic and molecular factors that contribute to heart failure by analyzing data from a large number of studies worldwide.
  • It includes 51 studies from 11 countries, gathering data from over 68,000 heart failure cases and nearly 950,000 controls, with broad demographic representation and long follow-up periods.
  • The main goals are to identify genetic risk factors for heart failure, explore causal pathways, and create tools to help stratify patients and predict risks based on their genetic information.
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Obesity-related inflammation is associated with cardiovascular, metabolic, and pulmonary diseases. The aim of this study was to demonstrate associations between adiposity measurements and levels of inflammation-related plasma proteins in a population of young adults. Subjects from a population-based birth cohort with a mean age of 22.

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