Noncoding SNPs associated with increased GDF15 levels located in a metformin-activated enhancer region upstream of GDF15
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 around GDF15. 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 and cis-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 for GDF15 expression in whole blood are located in a metformin-activated enhancer upstream of GDF15 and tightly linked in Europeans and East Asians. Conclusion: Noncoding variation within a metformin-activated enhancer may increase GDF15 expression and help to predict GDF15 levels.
| 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 vom: 02. Juni, Seite 509-520 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Linhares, Natália D [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 26.04.2021 Date Revised 26.04.2021 published: Print-Electronic Citation Status MEDLINE |
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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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| PPN (Katalog-ID): |
NLM310095522 |
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| 100 | 1 | |a Linhares, Natália D |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Noncoding SNPs associated with increased GDF15 levels located in a metformin-activated enhancer region upstream of GDF15 |
| 264 | 1 | |c 2020 | |
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| 500 | |a Date Completed 26.04.2021 | ||
| 500 | |a Date Revised 26.04.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 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 around GDF15. 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 and cis-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 for GDF15 expression in whole blood are located in a metformin-activated enhancer upstream of GDF15 and tightly linked in Europeans and East Asians. Conclusion: Noncoding variation within a metformin-activated enhancer may increase GDF15 expression and help to predict GDF15 levels | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a GDF15 | |
| 650 | 4 | |a SNPs | |
| 650 | 4 | |a chromatin immunoprecipitation sequencing | |
| 650 | 4 | |a enhancer elements | |
| 650 | 4 | |a histone marks | |
| 650 | 4 | |a intergenic regions | |
| 650 | 4 | |a metformin | |
| 650 | 4 | |a transcriptional regulatory elements | |
| 650 | 4 | |a type 2 diabetes | |
| 650 | 7 | |a GDF15 protein, human |2 NLM | |
| 650 | 7 | |a Growth Differentiation Factor 15 |2 NLM | |
| 650 | 7 | |a Hypoglycemic Agents |2 NLM | |
| 650 | 7 | |a Metformin |2 NLM | |
| 650 | 7 | |a 9100L32L2N |2 NLM | |
| 700 | 1 | |a Pereira, Daniela A |e verfasserin |4 aut | |
| 700 | 1 | |a Conceição, Izabela McA |e verfasserin |4 aut | |
| 700 | 1 | |a Franco, Glória R |e verfasserin |4 aut | |
| 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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