Expressive

rs11568819 - MMP7 - MMP20

Magnitude 2.2 · 8 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

  • 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

  • Whole Genome Sequence Analysis of the Plasma Proteome in Black Adults Provides Novel Insights into Cardiovascular Disease - Unknown journal (n.d.) · Unknown authors · PubMed 34814699

    ABSTRACT: Background: Plasma proteins are critical mediators of cardiovascular processes and are the targets of many drugs. Previous efforts to characterize the genetic architecture of the plasma proteome have been limited by a focus on individuals of European descent and leveraged genotyping arrays and imputation. Here we describe whole genome sequence analysis of the plasma proteome in individuals with greater African ancestry, increasing our power to identify novel genetic determinants. Methods: Proteomic profiling of 1,301 proteins was performed in 1852 Black adults from the Jackson Heart Study using aptamer-based proteomics (SomaScan®). Whole genome sequencing association analysis was ascertained for all variants with minor allele count ≥ 5. Results were validated using an alternat

  • Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals - Unknown journal (n.d.) · Unknown authors · PubMed 33067605

    ABSTRACT: Circulating proteins are vital in human health and disease and are frequently used as biomarkers for clinical decision-making or as targets for pharmacological intervention. Here we map and replicate protein quantitative trait loci (pQTL) for 90 cardiovascular proteins in over 30,000 individuals, resulting in 451 pQTLs for 85 proteins. For each protein we further perform pathway mapping to obtain trans-pQTL gene and regulatory designations. We substantiate these regulatory findings with orthogonal evidence for trans-pQTLs using mouse knock-down experiments (ABCA1, TRIB1) and clinical trial results (CCR2, CCR5), with consistent regulation. Finally we evaluate known drug targets, and suggest new target candidates or repositioning opportunities using Mendelian randomization. This id

  • The relative contribution of DNA methylation and genetic variants on protein biomarkers for human diseases - Unknown journal (n.d.) · Unknown authors · PubMed 28915241

    ABSTRACT: Associations between epigenetic alterations and disease status have been identified for many diseases. However, there is no strong evidence that epigenetic alterations are directly causal for disease pathogenesis. In this study, we combined SNP and DNA methylation data with measurements of protein biomarkers for cancer, inflammation or cardiovascular disease, to investigate the relative contribution of genetic and epigenetic variation on biomarker levels. A total of 121 protein biomarkers were measured and analyzed in relation to DNA methylation at 470,000 genomic positions and to over 10 million SNPs. We performed epigenome-wide association study (EWAS) and genome-wide association study (GWAS) analyses, and integrated biomarker, DNA methylation and SNP data using between 698 and

  • Identifying causal serum protein-cardiometabolic trait relationships using whole genome sequencing - Unknown journal (n.d.) · Unknown authors · PubMed 36349687

    ABSTRACT: Abstract Cardiometabolic diseases, such as type 2 diabetes and cardiovascular disease, have a high public health burden. Understanding the genetically determined regulation of proteins that are dysregulated in disease can help to dissect the complex biology underpinning them. Here, we perform a protein quantitative trait locus (pQTL) analysis of 248 serum proteins relevant to cardiometabolic processes in 2893 individuals. Meta-analyzing whole-genome sequencing (WGS) data from two Greek cohorts, MANOLIS (n = 1356; 22.5× WGS) and Pomak (n = 1537; 18.4× WGS), we detect 301 independently associated pQTL variants for 170 proteins, including 12 rare variants (minor allele frequency < 1%). We additionally find 15 pQTL variants that are rare in non-Finnish European populati

  • Connecting genetic risk to disease end points through the human blood plasma proteome - Unknown journal (n.d.) · Unknown authors · PubMed 28240269

    ABSTRACT: Genome-wide association studies (GWAS) with intermediate phenotypes, like changes in metabolite and protein levels, provide functional evidence to map disease associations and translate them into clinical applications. However, although hundreds of genetic variants have been associated with complex disorders, the underlying molecular pathways often remain elusive. Associations with intermediate traits are key in establishing functional links between GWAS-identified risk-variants and disease end points. Here we describe a GWAS using a highly multiplexed aptamer-based affinity proteomics platform. We quantify 539 associations between protein levels and gene variants (pQTLs) in a German cohort and replicate over half of them in an Arab and Asian cohort. Fifty-five of the replicated

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