Noncoding SNPs associated with increased GDF15 levels located in a metformin-activated enhancer region upstream ofGDF15 / Natália D Linhares, Daniela A Pereira, Izabela MCA Conceição, Glória R Franco, Walter L Eckalbar, Nadav Ahituv, Marcelo R Luizon
Aim:GDF15 levels are a biomarker for metformin use. We performed the functional annotation of noncoding genome-wide association study (GWAS) SNPs for GDF15 levels and the Genotype-Tissue Expression (GTEx)-expression quantitative trait loci (eQTLs) for GDF15 expression within metformin-activated enhancers aroundGDF15.Materials & methods:These enhancers were identified using chromatin immunoprecipitation followed by sequencing data for active (H3K27ac) and silenced (H3K27me3) histone marks on human hepatocytes treated with metformin, Encyclopedia of DNA Elements data andcis-regulatory elements assignment tools.Results:The GWAS lead SNP rs888663, the SNP rs62122429 associated with GDF15 levels in the Outcome Reduction with Initial Glargine Intervention trial, and the GTEx-expression quantitative trait locus rs4808791 forGDF15expression in whole blood are located in a metformin-activated enhancer upstream ofGDF15and tightly linked in Europeans and East Asians.Conclusion:Noncoding variation within a metformin-activated enhancer may increaseGDF15expression and help to predict GDF15 levels. Aim: GDF15 Materials & methods: cis Results: GDF15 GDF15 Conclusion: GDF15 Graphical abstract.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:21 |
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| Enthalten in: |
Pharmacogenomics - 21(2020), 8, Seite 509- |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Linhares, Natália D [VerfasserIn] |
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| Links: |
FID Access [lizenzpflichtig] |
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| Umfang: |
1 Online-Ressource (12 p) |
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| doi: |
10.2217/pgs-2020-0010 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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KFL001067540 |
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| 245 | 1 | 0 | |a Noncoding SNPs associated with increased GDF15 levels located in a metformin-activated enhancer region upstream ofGDF15 |c Natália D Linhares, Daniela A Pereira, Izabela MCA Conceição, Glória R Franco, Walter L Eckalbar, Nadav Ahituv, Marcelo R Luizon |
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| 520 | |a Aim:GDF15 levels are a biomarker for metformin use. We performed the functional annotation of noncoding genome-wide association study (GWAS) SNPs for GDF15 levels and the Genotype-Tissue Expression (GTEx)-expression quantitative trait loci (eQTLs) for GDF15 expression within metformin-activated enhancers aroundGDF15.Materials & methods:These enhancers were identified using chromatin immunoprecipitation followed by sequencing data for active (H3K27ac) and silenced (H3K27me3) histone marks on human hepatocytes treated with metformin, Encyclopedia of DNA Elements data andcis-regulatory elements assignment tools.Results:The GWAS lead SNP rs888663, the SNP rs62122429 associated with GDF15 levels in the Outcome Reduction with Initial Glargine Intervention trial, and the GTEx-expression quantitative trait locus rs4808791 forGDF15expression in whole blood are located in a metformin-activated enhancer upstream ofGDF15and tightly linked in Europeans and East Asians.Conclusion:Noncoding variation within a metformin-activated enhancer may increaseGDF15expression and help to predict GDF15 levels. Aim: GDF15 Materials & methods: cis Results: GDF15 GDF15 Conclusion: GDF15 Graphical abstract | ||
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| 700 | 1 | |a Eckalbar, Walter L |e verfasserin |4 aut | |
| 700 | 1 | |a Ahituv, Nadav |e verfasserin |4 aut | |
| 700 | 1 | |a Luizon, Marcelo R |e verfasserin |4 aut | |
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