DESCRIPTION:

List of positional candidate genes after correcting for multiple testing and controlling the false discovery rate from genome wide association studies (GWAS) retrieved from the NHGRI-EBI Catalog of published genome-wide association studies (http://www.ebi.ac.uk/gwas/). The disease/trait examined in this study, as reported by the authors, was Plasminogen activator inhibitor type 1 levels (PAI-1). The EFO term plasminogen activator inhibitor 1 measurement was annotated to this set after curation by NHGRI-EBI. Intergenic SNPS were mapped to both the upstream and downstream gene. P-value uploaded. This gene set was generated using gwas2gs v. 0.1.8 and the GWAS Catalog v. 1.0.1.

LABEL:

GWAS: plasminogen activator inhibitor 1 measurement

SCORE TYPE:

P-Value

DATE ADDED:

2017-05-02

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

J Huang, M Sabater-Lleal, FW Asselbergs, D Tregouet, SY Shin, J Ding, J Baumert, T Oudot-Mellakh, L Folkersen, AD Johnson, NL Smith, SM Williams, MA Ikram, ME Kleber, DM Becker, V Truong, JC Mychaleckyj, W Tang, Q Yang, B Sennblad, JH Moore, FM Williams, A Dehghan, G Silbernagel, EM Schrijvers, S Smith, M Karakas, GH Tofler, A Silveira, GJ Navis, K Lohman, MH Chen, A Peters, A Goel, JC Hopewell, JC Chambers, D Saleheen, P Lundmark, BM Psaty, RJ Strawbridge, BO Boehm, AM Carter, C Meisinger, JF Peden, JC Bis, B McKnight, J Öhrvik, K Taylor, MG Franzosi, U Seedorf, R Collins, A Franco-Cereceda, AC Syvänen, AH Goodall, LR Yanek, M Cushman, M Müller-Nurasyid, AR Folsom, S Basu, N Matijevic, WH van Gilst, JS Kooner, A Hofman, J Danesh, R Clarke, JB Meigs, S Kathiresan, MP Reilly, N Klopp, TB Harris, BR Winkelmann, PJ Grant, HL Hillege, H Watkins, TD Spector, LC Becker, RP Tracy, W März, AG Uitterlinden, P Eriksson, F Cambien, PE Morange, W Koenig, N Soranzo, P van der Harst, Y Liu, CJ O'Donnell, A Hamsten

TITLE:

Genome-wide association study for circulating levels of PAI-1 provides novel insights into its regulation.

JOURNAL:

Blood Dec 2012, Vol 120, pp. 4873-81

ABSTRACT:

We conducted a genome-wide association study to identify novel associations between genetic variants and circulating plasminogen activator inhibitor-1 (PAI-1) concentration, and examined functional implications of variants and genes that were discovered. A discovery meta-analysis was performed in 19 599 subjects, followed by replication analysis of genome-wide significant (P < 5 × 10(-8)) single nucleotide polymorphisms (SNPs) in 10 796 independent samples. We further examined associations with type 2 diabetes and coronary artery disease, assessed the functional significance of the SNPs for gene expression in human tissues, and conducted RNA-silencing experiments for one novel association. We confirmed the association of the 4G/5G proxy SNP rs2227631 in the promoter region of SERPINE1 (7q22.1) and discovered genome-wide significant associations at 3 additional loci: chromosome 7q22.1 close to SERPINE1 (rs6976053, discovery P = 3.4 × 10(-10)); chromosome 11p15.2 within ARNTL (rs6486122, discovery P = 3.0 × 10(-8)); and chromosome 3p25.2 within PPARG (rs11128603, discovery P = 2.9 × 10(-8)). Replication was achieved for the 7q22.1 and 11p15.2 loci. There was nominal association with type 2 diabetes and coronary artery disease at ARNTL (P < .05). Functional studies identified MUC3 as a candidate gene for the second association signal on 7q22.1. In summary, SNPs in SERPINE1 and ARNTL and an SNP associated with the expression of MUC3 were robustly associated with circulating levels of PAI-1. PUBMED: 22990020
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