Expressive

rs11553746 - ACP1

Magnitude 2.2 · 4 studies on file

Reported associations

  • Common coding variant in increases the risk for large artery stroke. - Proceedings of the National Academy of Sciences of the United States of America (2018) · Malik R, Dau T, Gonik M, Sivakumar A, Deredge DJ, Edeleva EV, Götzfried J, van der Laan SW, Pasterkamp G, Beaufort N, Seixas S, Bevan S, Lincz LF, Holliday EG, Burgess AI, Rannikmäe K, Minnerup J, Kriebel J, Waldenberger M, Müller-Nurasyid M, Lichtner P, Saleheen D, Rothwell PM, Levi C, Attia J, Sudlow CL, Braun D, Markus HS, Wintrode PL, Berger K, Jenne DE, Dichgans M · PubMed 28265093

    Large artery atherosclerotic stroke (LAS) shows substantial heritability not explained by previous genome-wide association studies. Here, we explore the role of coding variation in LAS by analyzing variants on the HumanExome BeadChip in a total of 3,127 cases and 9,778 controls from Europe, Australia, and South Asia. We report on a nonsynonymous single-nucleotide variant in serpin family A member 1 ( ) encoding alpha-1 antitrypsin [AAT; p.V213A; = 5.99E-9, odds ratio (OR) = 1.22] and confirm histone deacetylase 9 ( ) as a major risk gene for LAS with an association in the 3'-UTR (rs2023938; = 7.76E-7, OR = 1.28). Using quantitative microscale thermophoresis, we show that M1 (A213) exhibits an almost twofold lower dissociation constant with its primary target human neutrophil elastase (NE)

  • Genetic associations with ratios between protein levels detect new pQTLs and reveal protein-protein interactions - Unknown journal (n.d.) · Unknown authors · PubMed 38412862

    ABSTRACT: Summary Protein quantitative trait loci (pQTLs) are an invaluable source of information for drug target development because they provide genetic evidence to support protein function, suggest relationships between cis- and trans-associated proteins, and link proteins to disease endpoints. Using Olink proteomics data for 1,463 proteins measured in over 54,000 samples of the UK Biobank, we identified 4,248 associations with 2,821 ratios between protein levels (rQTLs). rQTLs were 7.6-fold enriched in known protein-protein interactions, suggesting that their ratios reflect biological links between the implicated proteins. Conducting a GWAS on ratios increased the number of discovered genetic signals by 24.7%. The approach can identify novel loci of clinical relevance, support causal g

  • Exome-wide association study of plasma lipids in >300,000 individuals - Unknown journal (n.d.) · Unknown authors · PubMed 29083408

    ABSTRACT: We screened DNA sequence variants on an exome-focused genotyping array in >300,000 participants with replication in >280,000 participants and identified 444 independent variants in 250 loci significantly associated with total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and/or triglycerides (TG). At two loci (JAK2 and A1CF), experimental analysis in mice revealed lipid changes consistent with the human data. We utilized mapped variants to address four clinically relevant questions and found the following: (1) beta-thalassemia trait carriers displayed lower TC and were protected from coronary artery disease; (2) outside of the CETP locus, there was not a predictable relationship between plasma HDL-C and risk for age-r

  • 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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