Expressive

rs1126605 - C1RL, C1R

Magnitude 2.2 · 6 studies on file

Reported associations

  • Proteogenomic analysis of human cerebrospinal fluid identifies neurologically relevant regulation and implicates causal proteins for Alzheimer's disease. - Nature genetics (2024) · Western D, Timsina J, Wang L, Wang C, Yang C, Phillips B, Wang Y, Liu M, Ali M, Beric A, Gorijala P, Kohlfeld P, Budde J, Levey AI, Morris JC, Perrin RJ, Ruiz A, Marquié M, Boada M, de Rojas I, Rutledge J, Oh H, Wilson EN, Le Guen Y, Reus LM, Tijms B, Visser PJ, van der Lee SJ, Pijnenburg YAL, Teunissen CE, Del Campo Milan M, Alvarez I, Aguilar M, Greicius MD, Pastor P, Pulford DJ, Ibanez L, Wyss-Coray T, Sung YJ, Cruchaga C · PubMed 39528825

    The integration of quantitative trait loci (QTLs) with disease genome-wide association studies (GWASs) has proven successful in prioritizing candidate genes at disease-associated loci. QTL mapping has been focused on multi-tissue expression QTLs or plasma protein QTLs (pQTLs). We generated a cerebrospinal fluid (CSF) pQTL atlas by measuring 6,361 proteins in 3,506 samples. We identified 3,885 associations for 1,883 proteins, including 2,885 new pQTLs, demonstrating unique genetic regulation in CSF. We identified CSF-enriched pleiotropic regions on chromosome (chr)3q28 near OSTN and chr19q13.32 near APOE that were enriched for neuron specificity and neurological development. We integrated our associations with Alzheimer's disease (AD) through proteome-wide association study (PWAS), colocali

  • Identification of 969 protein quantitative trait loci in an African American population with kidney disease attributed to hypertension. - Kidney international (2022) · Surapaneni A, Schlosser P, Zhou L, Liu C, Chatterjee N, Arking DE, Dutta D, Coresh J, Rhee EP, Grams ME · PubMed 35870639

    Investigations into the causal underpinnings of disease processes can be aided by the incorporation of genetic information. Genetic studies require populations varied in both ancestry and prevalent disease in order to optimize discovery and ensure generalizability of findings to the global population. Here, we report the genetic determinants of the serum proteome in 466 African Americans with chronic kidney disease attributed to hypertension from the richly phenotyped African American Study of Kidney Disease and Hypertension (AASK) study. Using the largest aptamer-based protein profiling platform to date (6,790 proteins or protein complexes), we identified 969 genetic associations with 900 unique proteins; including 52 novel cis (local) associations and 379 novel trans (distant) associatio

  • Efficient candidate drug target discovery through proteogenomics in a Scottish cohort - Unknown journal (n.d.) · Unknown authors · PubMed 40883583

    ABSTRACT: Understanding the genomic basis of human proteomic variability provides powerful tools to probe potential causal relationships of proteins and disease risk, and thus to prioritise candidate drug targets. Here, we investigated 6432 plasma proteins (1533 previously unstudied in large-scale proteomic GWAS) using the SomaLogic (v4.1) aptamer-based technology in a Scottish population from the Viking Genes study. A total of 505 significant independent protein quantitative trait loci (pQTL) were found for 455 proteins in blood plasma: 382 cis- (P < 5×10-8) and 123 trans- (P < 6.6×10-12). Of these, 31 cis-pQTL were for proteins with no previous GWAS. We leveraged these pQTL to perform causal inference using bidirectional Mendelian randomisation and colocalisation against comple

  • Genomic atlas of the human plasma proteome - Unknown journal (n.d.) · Unknown authors · PubMed 29875488

    ABSTRACT: Although plasma proteins have important roles in biological processes and are the direct targets of many drugs, the genetic factors that control inter-individual variation in plasma protein levels are not well understood. Here we characterize the genetic architecture of the human plasma proteome in healthy blood donors from the INTERVAL study. We identify 1,927 genetic associations with 1,478 proteins, a fourfold increase on existing knowledge, including trans associations for 1,104 proteins. To understand the consequences of perturbations in plasma protein levels, we apply an integrated approach that links genetic variation with biological pathway, disease, and drug databases. We show that protein quantitative trait loci overlap with gene expression quantitative trait loci, as w

  • Mapping the proteo-genomic convergence of human diseases - Unknown journal (n.d.) · Unknown authors · PubMed 34648354

    ABSTRACT: Characterization of the genetic regulation of proteins is essential for understanding disease etiology and developing therapies. We identified 10,674 genetic associations for 3,892 plasma proteins to create a cis-anchored gene-protein-disease map of 1,859 connections that highlights strong cross-disease biological convergence. This proteo-genomic map provides a framework to 1) connect etiologically related diseases, 2) provide biological context for new or emerging disorders, and 3) integrate different biological domains to establish mechanisms for known gene-disease links. Our results identify proteo-genomic connections within and between diseases and establish the value of cis-protein variants for annotation of likely causal disease genes at GWAS loci, addressing a major barrie

  • A genome-wide association study of serum proteins reveals shared loci with common diseases - Unknown journal (n.d.) · Unknown authors · PubMed 35078996

    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

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