Expressive

rs11639051 - PCSK6

Magnitude 2.0 · 4 studies on file

Reported associations

  • An expanded analysis framework for multivariate GWAS connects inflammatory biomarkers to functional variants and disease. - European journal of human genetics : EJHG (2022) · Ruotsalainen SE, Partanen JJ, Cichonska A, Lin J, Benner C, Surakka I, Reeve MP, Palta P, Salmi M, Jalkanen S, Ahola-Olli A, Palotie A, Salomaa V, Daly MJ, Pirinen M, Ripatti S, Koskela J · PubMed 33110245

    Multivariate methods are known to increase the statistical power to detect associations in the case of shared genetic basis between phenotypes. They have, however, lacked essential analytic tools to follow-up and understand the biology underlying these associations. We developed a novel computational workflow for multivariate GWAS follow-up analyses, including fine-mapping and identification of the subset of traits driving associations (driver traits). Many follow-up tools require univariate regression coefficients which are lacking from multivariate results. Our method overcomes this problem by using Canonical Correlation Analysis to turn each multivariate association into its optimal univariate Linear Combination Phenotype (LCP). This enables an LCP-GWAS, which in turn generates the stat

  • Multivariate Genome-wide Association Analysis of a Cytokine Network Reveals Variants with Widespread Immune, Haematological, and Cardiometabolic Pleiotropy. - American journal of human genetics (2020) · Nath AP, Ritchie SC, Grinberg NF, Tang HH, Huang QQ, Teo SM, Ahola-Olli AV, Würtz P, Havulinna AS, Santalahti K, Pitkänen N, Lehtimäki T, Kähönen M, Lyytikäinen LP, Raitoharju E, Seppälä I, Sarin AP, Ripatti S, Palotie A, Perola M, Viikari JS, Jalkanen S, Maksimow M, Salmi M, Wallace C, Raitakari OT, Salomaa V, Abraham G, Kettunen J, Inouye M · PubMed 31679650

    Cytokines are essential regulatory components of the immune system, and their aberrant levels have been linked to many disease states. Despite increasing evidence that cytokines operate in concert, many of the physiological interactions between cytokines, and the shared genetic architecture that underlies them, remain unknown. Here, we aimed to identify and characterize genetic variants with pleiotropic effects on cytokines. Using three population-based cohorts (n = 9,263), we performed multivariate genome-wide association studies (GWAS) for a correlation network of 11 circulating cytokines, then combined our results in meta-analysis. We identified a total of eight loci significantly associated with the cytokine network, of which two (PDGFRB and ABO) had not been detected previously. In ad

  • A scalable variational inference approach for increased mixed-model association power - Unknown journal (n.d.) · Unknown authors · PubMed 39789286

    ABSTRACT: The rapid growth of modern biobanks is creating new opportunities for large-scale genome-wide association studies (GWASs) and the analysis of complex traits. However, performing GWASs on millions of samples often leads to trade-offs between computational efficiency and statistical power, reducing the benefits of large-scale data collection efforts. We developed Quickdraws, a method that increases association power in quantitative and binary traits without sacrificing computational efficiency, leveraging a spike-and-slab prior on variant effects, stochastic variational inference and graphics processing unit acceleration. We applied Quickdraws to 79 quantitative and 50 binary traits in 405,088 UK Biobank samples, identifying 4.97% and 3.25% more associations than REGENIE and 22.71%

  • 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

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