Autoimmune diseases association study with the KIAA1109-IL2-IL21region in a Tunisian population

Bouzid, Dorra; Fourati, H.; Amouri, A.; Isabel, Marques; Abida, Olfa; Tahri, N.; Carlos, Penha-Gonalves; Masmoudi, Hatem

doi:10.3389/conf.fimmu.2013.02.00529

Cited by 2 publications

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“…2d). These traits are clinically related [63] and colocalized at 13 loci (Additional file 1: Table S18), including sites near genes that regulate eosinophil biology (ETS1 [64,65] and ID2 [65]) and autoimmune disease (KIAA1109 [66][67][68] and TAGAP [69]). These colocalization sites also indicated potential regulation of unexpected genes that warrant validation (SNX32, ZNF652, KLC2).…”

Section: Illuminating Hematopoietic Contributions and Associations Wimentioning

confidence: 99%

Genetic colocalization atlas points to common regulatory sites and genes for hematopoietic traits and hematopoietic contributions to disease phenotypes

Thom

Voight

2020

BMC Med Genomics

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Background: Genetic associations link hematopoietic traits and disease end-points, but most causal variants and genes underlying these relationships are unknown. Here, we used genetic colocalization to nominate loci and genes related to shared genetic signal for hematopoietic, cardiovascular, autoimmune, neuropsychiatric, and cancer phenotypes. Methods: Our aim was to identify colocalization sites for human traits among established genome-wide significant loci. Using genome-wide association study (GWAS) summary statistics, we determined loci where multiple traits colocalized at a false discovery rate < 5%. We then identified quantitative trait loci among colocalization sites to highlight related genes. In addition, we used Mendelian randomization analysis to further investigate certain trait relationships genome-wide. Results: Our findings recapitulated developmental hematopoietic lineage relationships, identified loci that linked traits with causal genetic relationships, and revealed novel trait associations. Out of 2706 loci with genome-wide significant signal for at least 1 blood trait, we identified 1779 unique sites (66%) with shared genetic signal for 2+ hematologic traits. We could assign some sites to specific developmental cell types during hematopoiesis based on affected traits, including those likely to impact hematopoietic progenitor cells and/or megakaryocyte-erythroid progenitor cells. Through an expanded analysis of 70 human traits, we defined 2+ colocalizing traits at 2123 loci from an analysis of 9852 sites (22%) containing genome-wide significant signal for at least 1 GWAS trait. In addition to variants and genes underlying shared genetic signal between blood traits and disease phenotypes that had been previously related through Mendelian randomization studies, we defined loci and related genes underlying shared signal between eosinophil percentage and eczema. We also identified colocalizing signals in a number of clinically relevant coding mutations, including sites linking PTPN22 with Crohn's disease, NIPA with coronary artery disease and platelet trait variation, and the hemochromatosis gene HFE with altered lipid levels. Finally, we anticipate potential off-target effects on blood traits related novel therapeutic targets, including TRAIL.

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Section: Illuminating Hematopoietic Contributions and Associations Wimentioning

confidence: 99%

Genetic colocalization atlas points to common regulatory sites and genes for hematopoietic traits and hematopoietic contributions to disease phenotypes

Thom

Voight

2020

BMC Med Genomics

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Genetic colocalization atlas points to common regulatory sites and genes for hematopoietic traits and hematopoietic contributions to disease phenotypes

Thom

Voight

2019

Preprint

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Genetic associations link hematopoietic traits and disease end-points, but most causal variants and genes underlying these relationships are unknown. We used genetic colocalization to pinpoint loci regulating hematopoietic, cardiovascular, autoimmune, neuropsychiatric and cancer phenotypes. Our findings recapitulate developmental relationships between hematopoietic traits, identify quantitative trait loci (QTLs) relating traits with known causal genetic relationships, and reveal novel genetic associations between disease phenotypes, providing a road map for gene validation experiments.

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Autoimmune diseases association study with the KIAA1109-IL2-IL21region in a Tunisian population

Cited by 2 publications

References 0 publications

Genetic colocalization atlas points to common regulatory sites and genes for hematopoietic traits and hematopoietic contributions to disease phenotypes

Genetic colocalization atlas points to common regulatory sites and genes for hematopoietic traits and hematopoietic contributions to disease phenotypes

Genetic colocalization atlas points to common regulatory sites and genes for hematopoietic traits and hematopoietic contributions to disease phenotypes

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