Identification of loci of functional relevance to Barrett's esophagus and esophageal adenocarcinoma: Cross-referencing of expression quantitative trait loci data from disease-relevant tissues with genetic association data.
Esophageal adenocarcinoma (EA) and its precancerous condition Barrett's esophagus (BE) are multifactorial diseases with rising prevalence rates in Western populations. A recent meta-analysis of genome-wide association studies (GWAS) data identified 14 BE/EA risk loci located in non-coding genom...
Ausführliche Beschreibung
Autor*in: |
Julia Schröder [verfasserIn] Vitalia Schüller [verfasserIn] Andrea May [verfasserIn] Christian Gerges [verfasserIn] Mario Anders [verfasserIn] Jessica Becker [verfasserIn] Timo Hess [verfasserIn] Nicole Kreuser [verfasserIn] René Thieme [verfasserIn] Kerstin U Ludwig [verfasserIn] Tania Noder [verfasserIn] Marino Venerito [verfasserIn] Lothar Veits [verfasserIn] Thomas Schmidt [verfasserIn] Claudia Fuchs [verfasserIn] Jakob R Izbicki [verfasserIn] Arnulf H Hölscher [verfasserIn] Dani Dakkak [verfasserIn] Boris Jansen-Winkeln [verfasserIn] Yusef Moulla [verfasserIn] Orestis Lyros [verfasserIn] Stefan Niebisch [verfasserIn] Matthias Mehdorn [verfasserIn] Hauke Lang [verfasserIn] Dietmar Lorenz [verfasserIn] Brigitte Schumacher [verfasserIn] Rupert Mayershofer [verfasserIn] Yogesh Vashist [verfasserIn] Katja Ott [verfasserIn] Michael Vieth [verfasserIn] Josef Weismüller [verfasserIn] Elisabeth Mangold [verfasserIn] Markus M Nöthen [verfasserIn] Susanne Moebus [verfasserIn] Michael Knapp [verfasserIn] Horst Neuhaus [verfasserIn] Thomas Rösch [verfasserIn] Christian Ell [verfasserIn] Ines Gockel [verfasserIn] Johannes Schumacher [verfasserIn] Anne C Böhmer [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2019 |
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Übergeordnetes Werk: |
In: PLoS ONE - Public Library of Science (PLoS), 2007, 14(2019), 12, p e0227072 |
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Übergeordnetes Werk: |
volume:14 ; year:2019 ; number:12, p e0227072 |
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DOI / URN: |
10.1371/journal.pone.0227072 |
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Katalog-ID: |
DOAJ059607122 |
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245 | 1 | 0 | |a Identification of loci of functional relevance to Barrett's esophagus and esophageal adenocarcinoma: Cross-referencing of expression quantitative trait loci data from disease-relevant tissues with genetic association data. |
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520 | |a Esophageal adenocarcinoma (EA) and its precancerous condition Barrett's esophagus (BE) are multifactorial diseases with rising prevalence rates in Western populations. A recent meta-analysis of genome-wide association studies (GWAS) data identified 14 BE/EA risk loci located in non-coding genomic regions. Knowledge about the impact of non-coding variation on disease pathology is incomplete and needs further investigation. The aim of the present study was (i) to identify candidate genes of functional relevance to BE/EA at known risk loci and (ii) to find novel risk loci among the suggestively associated variants through the integration of expression quantitative trait loci (eQTL) and genetic association data. eQTL data from two BE/EA-relevant tissues (esophageal mucosa and gastroesophageal junction) generated within the context of the GTEx project were cross-referenced with the GWAS meta-analysis data. Variants representing an eQTL in at least one of the two tissues were categorized into genome-wide significant loci (P < 5×10-8) and novel candidate loci (5×10-8 ≤ P ≤ 5×10-5). To follow up these novel candidate loci, a genetic association study was performed in a replication cohort comprising 1,993 cases and 967 controls followed by a combined analysis with the GWAS meta-analysis data. The cross-referencing of eQTL and genetic data yielded 2,180 variants that represented 25 loci. Among the previously reported genome-wide significant loci, 22 eQTLs were identified in esophageal mucosa and/or gastroesophageal junction tissue. The regulated genes, most of which have not been linked to BE/EA etiology so far, included C2orf43/LDAH, ZFP57, and SLC9A3. Among the novel candidate loci, replication was achieved for two variants (rs7754014, Pcombined = 3.16×10-7 and rs1540, Pcombined = 4.16×10-6) which represent eQTLs for CFDP1 and SLC22A3, respectively. In summary, the present approach identified candidate genes whose expression was regulated by risk variants in disease-relevant tissues. These findings may facilitate the elucidation of BE/EA pathophysiology. | ||
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10.1371/journal.pone.0227072 doi (DE-627)DOAJ059607122 (DE-599)DOAJ9c36f8077f394aafb298ab13e918fae3 DE-627 ger DE-627 rakwb eng Julia Schröder verfasserin aut Identification of loci of functional relevance to Barrett's esophagus and esophageal adenocarcinoma: Cross-referencing of expression quantitative trait loci data from disease-relevant tissues with genetic association data. 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Esophageal adenocarcinoma (EA) and its precancerous condition Barrett's esophagus (BE) are multifactorial diseases with rising prevalence rates in Western populations. A recent meta-analysis of genome-wide association studies (GWAS) data identified 14 BE/EA risk loci located in non-coding genomic regions. Knowledge about the impact of non-coding variation on disease pathology is incomplete and needs further investigation. The aim of the present study was (i) to identify candidate genes of functional relevance to BE/EA at known risk loci and (ii) to find novel risk loci among the suggestively associated variants through the integration of expression quantitative trait loci (eQTL) and genetic association data. eQTL data from two BE/EA-relevant tissues (esophageal mucosa and gastroesophageal junction) generated within the context of the GTEx project were cross-referenced with the GWAS meta-analysis data. Variants representing an eQTL in at least one of the two tissues were categorized into genome-wide significant loci (P < 5×10-8) and novel candidate loci (5×10-8 ≤ P ≤ 5×10-5). To follow up these novel candidate loci, a genetic association study was performed in a replication cohort comprising 1,993 cases and 967 controls followed by a combined analysis with the GWAS meta-analysis data. The cross-referencing of eQTL and genetic data yielded 2,180 variants that represented 25 loci. Among the previously reported genome-wide significant loci, 22 eQTLs were identified in esophageal mucosa and/or gastroesophageal junction tissue. The regulated genes, most of which have not been linked to BE/EA etiology so far, included C2orf43/LDAH, ZFP57, and SLC9A3. Among the novel candidate loci, replication was achieved for two variants (rs7754014, Pcombined = 3.16×10-7 and rs1540, Pcombined = 4.16×10-6) which represent eQTLs for CFDP1 and SLC22A3, respectively. In summary, the present approach identified candidate genes whose expression was regulated by risk variants in disease-relevant tissues. These findings may facilitate the elucidation of BE/EA pathophysiology. Medicine R Science Q Vitalia Schüller verfasserin aut Andrea May verfasserin aut Christian Gerges verfasserin aut Mario Anders verfasserin aut Jessica Becker verfasserin aut Timo Hess verfasserin aut Nicole Kreuser verfasserin aut René Thieme verfasserin aut Kerstin U Ludwig verfasserin aut Tania Noder verfasserin aut Marino Venerito verfasserin aut Lothar Veits verfasserin aut Thomas Schmidt verfasserin aut Claudia Fuchs verfasserin aut Jakob R Izbicki verfasserin aut Arnulf H Hölscher verfasserin aut Dani Dakkak verfasserin aut Boris Jansen-Winkeln verfasserin aut Yusef Moulla verfasserin aut Orestis Lyros verfasserin aut Stefan Niebisch verfasserin aut Matthias Mehdorn verfasserin aut Hauke Lang verfasserin aut Dietmar Lorenz verfasserin aut Brigitte Schumacher verfasserin aut Rupert Mayershofer verfasserin aut Yogesh Vashist verfasserin aut Katja Ott verfasserin aut Michael Vieth verfasserin aut Josef Weismüller verfasserin aut Elisabeth Mangold verfasserin aut Markus M Nöthen verfasserin aut Susanne Moebus verfasserin aut Michael Knapp verfasserin aut Horst Neuhaus verfasserin aut Thomas Rösch verfasserin aut Christian Ell verfasserin aut Ines Gockel verfasserin aut Johannes Schumacher verfasserin aut Anne C Böhmer verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 14(2019), 12, p e0227072 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:14 year:2019 number:12, p e0227072 https://doi.org/10.1371/journal.pone.0227072 kostenfrei https://doaj.org/article/9c36f8077f394aafb298ab13e918fae3 kostenfrei https://doi.org/10.1371/journal.pone.0227072 kostenfrei https://doaj.org/toc/1932-6203 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_34 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_235 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2019 12, p e0227072 |
spelling |
10.1371/journal.pone.0227072 doi (DE-627)DOAJ059607122 (DE-599)DOAJ9c36f8077f394aafb298ab13e918fae3 DE-627 ger DE-627 rakwb eng Julia Schröder verfasserin aut Identification of loci of functional relevance to Barrett's esophagus and esophageal adenocarcinoma: Cross-referencing of expression quantitative trait loci data from disease-relevant tissues with genetic association data. 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Esophageal adenocarcinoma (EA) and its precancerous condition Barrett's esophagus (BE) are multifactorial diseases with rising prevalence rates in Western populations. A recent meta-analysis of genome-wide association studies (GWAS) data identified 14 BE/EA risk loci located in non-coding genomic regions. Knowledge about the impact of non-coding variation on disease pathology is incomplete and needs further investigation. The aim of the present study was (i) to identify candidate genes of functional relevance to BE/EA at known risk loci and (ii) to find novel risk loci among the suggestively associated variants through the integration of expression quantitative trait loci (eQTL) and genetic association data. eQTL data from two BE/EA-relevant tissues (esophageal mucosa and gastroesophageal junction) generated within the context of the GTEx project were cross-referenced with the GWAS meta-analysis data. Variants representing an eQTL in at least one of the two tissues were categorized into genome-wide significant loci (P < 5×10-8) and novel candidate loci (5×10-8 ≤ P ≤ 5×10-5). To follow up these novel candidate loci, a genetic association study was performed in a replication cohort comprising 1,993 cases and 967 controls followed by a combined analysis with the GWAS meta-analysis data. The cross-referencing of eQTL and genetic data yielded 2,180 variants that represented 25 loci. Among the previously reported genome-wide significant loci, 22 eQTLs were identified in esophageal mucosa and/or gastroesophageal junction tissue. The regulated genes, most of which have not been linked to BE/EA etiology so far, included C2orf43/LDAH, ZFP57, and SLC9A3. Among the novel candidate loci, replication was achieved for two variants (rs7754014, Pcombined = 3.16×10-7 and rs1540, Pcombined = 4.16×10-6) which represent eQTLs for CFDP1 and SLC22A3, respectively. In summary, the present approach identified candidate genes whose expression was regulated by risk variants in disease-relevant tissues. These findings may facilitate the elucidation of BE/EA pathophysiology. Medicine R Science Q Vitalia Schüller verfasserin aut Andrea May verfasserin aut Christian Gerges verfasserin aut Mario Anders verfasserin aut Jessica Becker verfasserin aut Timo Hess verfasserin aut Nicole Kreuser verfasserin aut René Thieme verfasserin aut Kerstin U Ludwig verfasserin aut Tania Noder verfasserin aut Marino Venerito verfasserin aut Lothar Veits verfasserin aut Thomas Schmidt verfasserin aut Claudia Fuchs verfasserin aut Jakob R Izbicki verfasserin aut Arnulf H Hölscher verfasserin aut Dani Dakkak verfasserin aut Boris Jansen-Winkeln verfasserin aut Yusef Moulla verfasserin aut Orestis Lyros verfasserin aut Stefan Niebisch verfasserin aut Matthias Mehdorn verfasserin aut Hauke Lang verfasserin aut Dietmar Lorenz verfasserin aut Brigitte Schumacher verfasserin aut Rupert Mayershofer verfasserin aut Yogesh Vashist verfasserin aut Katja Ott verfasserin aut Michael Vieth verfasserin aut Josef Weismüller verfasserin aut Elisabeth Mangold verfasserin aut Markus M Nöthen verfasserin aut Susanne Moebus verfasserin aut Michael Knapp verfasserin aut Horst Neuhaus verfasserin aut Thomas Rösch verfasserin aut Christian Ell verfasserin aut Ines Gockel verfasserin aut Johannes Schumacher verfasserin aut Anne C Böhmer verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 14(2019), 12, p e0227072 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:14 year:2019 number:12, p e0227072 https://doi.org/10.1371/journal.pone.0227072 kostenfrei https://doaj.org/article/9c36f8077f394aafb298ab13e918fae3 kostenfrei https://doi.org/10.1371/journal.pone.0227072 kostenfrei https://doaj.org/toc/1932-6203 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_34 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_235 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2019 12, p e0227072 |
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10.1371/journal.pone.0227072 doi (DE-627)DOAJ059607122 (DE-599)DOAJ9c36f8077f394aafb298ab13e918fae3 DE-627 ger DE-627 rakwb eng Julia Schröder verfasserin aut Identification of loci of functional relevance to Barrett's esophagus and esophageal adenocarcinoma: Cross-referencing of expression quantitative trait loci data from disease-relevant tissues with genetic association data. 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Esophageal adenocarcinoma (EA) and its precancerous condition Barrett's esophagus (BE) are multifactorial diseases with rising prevalence rates in Western populations. A recent meta-analysis of genome-wide association studies (GWAS) data identified 14 BE/EA risk loci located in non-coding genomic regions. Knowledge about the impact of non-coding variation on disease pathology is incomplete and needs further investigation. The aim of the present study was (i) to identify candidate genes of functional relevance to BE/EA at known risk loci and (ii) to find novel risk loci among the suggestively associated variants through the integration of expression quantitative trait loci (eQTL) and genetic association data. eQTL data from two BE/EA-relevant tissues (esophageal mucosa and gastroesophageal junction) generated within the context of the GTEx project were cross-referenced with the GWAS meta-analysis data. Variants representing an eQTL in at least one of the two tissues were categorized into genome-wide significant loci (P < 5×10-8) and novel candidate loci (5×10-8 ≤ P ≤ 5×10-5). To follow up these novel candidate loci, a genetic association study was performed in a replication cohort comprising 1,993 cases and 967 controls followed by a combined analysis with the GWAS meta-analysis data. The cross-referencing of eQTL and genetic data yielded 2,180 variants that represented 25 loci. Among the previously reported genome-wide significant loci, 22 eQTLs were identified in esophageal mucosa and/or gastroesophageal junction tissue. The regulated genes, most of which have not been linked to BE/EA etiology so far, included C2orf43/LDAH, ZFP57, and SLC9A3. Among the novel candidate loci, replication was achieved for two variants (rs7754014, Pcombined = 3.16×10-7 and rs1540, Pcombined = 4.16×10-6) which represent eQTLs for CFDP1 and SLC22A3, respectively. In summary, the present approach identified candidate genes whose expression was regulated by risk variants in disease-relevant tissues. These findings may facilitate the elucidation of BE/EA pathophysiology. Medicine R Science Q Vitalia Schüller verfasserin aut Andrea May verfasserin aut Christian Gerges verfasserin aut Mario Anders verfasserin aut Jessica Becker verfasserin aut Timo Hess verfasserin aut Nicole Kreuser verfasserin aut René Thieme verfasserin aut Kerstin U Ludwig verfasserin aut Tania Noder verfasserin aut Marino Venerito verfasserin aut Lothar Veits verfasserin aut Thomas Schmidt verfasserin aut Claudia Fuchs verfasserin aut Jakob R Izbicki verfasserin aut Arnulf H Hölscher verfasserin aut Dani Dakkak verfasserin aut Boris Jansen-Winkeln verfasserin aut Yusef Moulla verfasserin aut Orestis Lyros verfasserin aut Stefan Niebisch verfasserin aut Matthias Mehdorn verfasserin aut Hauke Lang verfasserin aut Dietmar Lorenz verfasserin aut Brigitte Schumacher verfasserin aut Rupert Mayershofer verfasserin aut Yogesh Vashist verfasserin aut Katja Ott verfasserin aut Michael Vieth verfasserin aut Josef Weismüller verfasserin aut Elisabeth Mangold verfasserin aut Markus M Nöthen verfasserin aut Susanne Moebus verfasserin aut Michael Knapp verfasserin aut Horst Neuhaus verfasserin aut Thomas Rösch verfasserin aut Christian Ell verfasserin aut Ines Gockel verfasserin aut Johannes Schumacher verfasserin aut Anne C Böhmer verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 14(2019), 12, p e0227072 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:14 year:2019 number:12, p e0227072 https://doi.org/10.1371/journal.pone.0227072 kostenfrei https://doaj.org/article/9c36f8077f394aafb298ab13e918fae3 kostenfrei https://doi.org/10.1371/journal.pone.0227072 kostenfrei https://doaj.org/toc/1932-6203 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_34 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_235 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2019 12, p e0227072 |
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10.1371/journal.pone.0227072 doi (DE-627)DOAJ059607122 (DE-599)DOAJ9c36f8077f394aafb298ab13e918fae3 DE-627 ger DE-627 rakwb eng Julia Schröder verfasserin aut Identification of loci of functional relevance to Barrett's esophagus and esophageal adenocarcinoma: Cross-referencing of expression quantitative trait loci data from disease-relevant tissues with genetic association data. 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Esophageal adenocarcinoma (EA) and its precancerous condition Barrett's esophagus (BE) are multifactorial diseases with rising prevalence rates in Western populations. A recent meta-analysis of genome-wide association studies (GWAS) data identified 14 BE/EA risk loci located in non-coding genomic regions. Knowledge about the impact of non-coding variation on disease pathology is incomplete and needs further investigation. The aim of the present study was (i) to identify candidate genes of functional relevance to BE/EA at known risk loci and (ii) to find novel risk loci among the suggestively associated variants through the integration of expression quantitative trait loci (eQTL) and genetic association data. eQTL data from two BE/EA-relevant tissues (esophageal mucosa and gastroesophageal junction) generated within the context of the GTEx project were cross-referenced with the GWAS meta-analysis data. Variants representing an eQTL in at least one of the two tissues were categorized into genome-wide significant loci (P < 5×10-8) and novel candidate loci (5×10-8 ≤ P ≤ 5×10-5). To follow up these novel candidate loci, a genetic association study was performed in a replication cohort comprising 1,993 cases and 967 controls followed by a combined analysis with the GWAS meta-analysis data. The cross-referencing of eQTL and genetic data yielded 2,180 variants that represented 25 loci. Among the previously reported genome-wide significant loci, 22 eQTLs were identified in esophageal mucosa and/or gastroesophageal junction tissue. The regulated genes, most of which have not been linked to BE/EA etiology so far, included C2orf43/LDAH, ZFP57, and SLC9A3. Among the novel candidate loci, replication was achieved for two variants (rs7754014, Pcombined = 3.16×10-7 and rs1540, Pcombined = 4.16×10-6) which represent eQTLs for CFDP1 and SLC22A3, respectively. In summary, the present approach identified candidate genes whose expression was regulated by risk variants in disease-relevant tissues. These findings may facilitate the elucidation of BE/EA pathophysiology. Medicine R Science Q Vitalia Schüller verfasserin aut Andrea May verfasserin aut Christian Gerges verfasserin aut Mario Anders verfasserin aut Jessica Becker verfasserin aut Timo Hess verfasserin aut Nicole Kreuser verfasserin aut René Thieme verfasserin aut Kerstin U Ludwig verfasserin aut Tania Noder verfasserin aut Marino Venerito verfasserin aut Lothar Veits verfasserin aut Thomas Schmidt verfasserin aut Claudia Fuchs verfasserin aut Jakob R Izbicki verfasserin aut Arnulf H Hölscher verfasserin aut Dani Dakkak verfasserin aut Boris Jansen-Winkeln verfasserin aut Yusef Moulla verfasserin aut Orestis Lyros verfasserin aut Stefan Niebisch verfasserin aut Matthias Mehdorn verfasserin aut Hauke Lang verfasserin aut Dietmar Lorenz verfasserin aut Brigitte Schumacher verfasserin aut Rupert Mayershofer verfasserin aut Yogesh Vashist verfasserin aut Katja Ott verfasserin aut Michael Vieth verfasserin aut Josef Weismüller verfasserin aut Elisabeth Mangold verfasserin aut Markus M Nöthen verfasserin aut Susanne Moebus verfasserin aut Michael Knapp verfasserin aut Horst Neuhaus verfasserin aut Thomas Rösch verfasserin aut Christian Ell verfasserin aut Ines Gockel verfasserin aut Johannes Schumacher verfasserin aut Anne C Böhmer verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 14(2019), 12, p e0227072 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:14 year:2019 number:12, p e0227072 https://doi.org/10.1371/journal.pone.0227072 kostenfrei https://doaj.org/article/9c36f8077f394aafb298ab13e918fae3 kostenfrei https://doi.org/10.1371/journal.pone.0227072 kostenfrei https://doaj.org/toc/1932-6203 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_34 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_235 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2019 12, p e0227072 |
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10.1371/journal.pone.0227072 doi (DE-627)DOAJ059607122 (DE-599)DOAJ9c36f8077f394aafb298ab13e918fae3 DE-627 ger DE-627 rakwb eng Julia Schröder verfasserin aut Identification of loci of functional relevance to Barrett's esophagus and esophageal adenocarcinoma: Cross-referencing of expression quantitative trait loci data from disease-relevant tissues with genetic association data. 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Esophageal adenocarcinoma (EA) and its precancerous condition Barrett's esophagus (BE) are multifactorial diseases with rising prevalence rates in Western populations. A recent meta-analysis of genome-wide association studies (GWAS) data identified 14 BE/EA risk loci located in non-coding genomic regions. Knowledge about the impact of non-coding variation on disease pathology is incomplete and needs further investigation. The aim of the present study was (i) to identify candidate genes of functional relevance to BE/EA at known risk loci and (ii) to find novel risk loci among the suggestively associated variants through the integration of expression quantitative trait loci (eQTL) and genetic association data. eQTL data from two BE/EA-relevant tissues (esophageal mucosa and gastroesophageal junction) generated within the context of the GTEx project were cross-referenced with the GWAS meta-analysis data. Variants representing an eQTL in at least one of the two tissues were categorized into genome-wide significant loci (P < 5×10-8) and novel candidate loci (5×10-8 ≤ P ≤ 5×10-5). To follow up these novel candidate loci, a genetic association study was performed in a replication cohort comprising 1,993 cases and 967 controls followed by a combined analysis with the GWAS meta-analysis data. The cross-referencing of eQTL and genetic data yielded 2,180 variants that represented 25 loci. Among the previously reported genome-wide significant loci, 22 eQTLs were identified in esophageal mucosa and/or gastroesophageal junction tissue. The regulated genes, most of which have not been linked to BE/EA etiology so far, included C2orf43/LDAH, ZFP57, and SLC9A3. Among the novel candidate loci, replication was achieved for two variants (rs7754014, Pcombined = 3.16×10-7 and rs1540, Pcombined = 4.16×10-6) which represent eQTLs for CFDP1 and SLC22A3, respectively. In summary, the present approach identified candidate genes whose expression was regulated by risk variants in disease-relevant tissues. These findings may facilitate the elucidation of BE/EA pathophysiology. Medicine R Science Q Vitalia Schüller verfasserin aut Andrea May verfasserin aut Christian Gerges verfasserin aut Mario Anders verfasserin aut Jessica Becker verfasserin aut Timo Hess verfasserin aut Nicole Kreuser verfasserin aut René Thieme verfasserin aut Kerstin U Ludwig verfasserin aut Tania Noder verfasserin aut Marino Venerito verfasserin aut Lothar Veits verfasserin aut Thomas Schmidt verfasserin aut Claudia Fuchs verfasserin aut Jakob R Izbicki verfasserin aut Arnulf H Hölscher verfasserin aut Dani Dakkak verfasserin aut Boris Jansen-Winkeln verfasserin aut Yusef Moulla verfasserin aut Orestis Lyros verfasserin aut Stefan Niebisch verfasserin aut Matthias Mehdorn verfasserin aut Hauke Lang verfasserin aut Dietmar Lorenz verfasserin aut Brigitte Schumacher verfasserin aut Rupert Mayershofer verfasserin aut Yogesh Vashist verfasserin aut Katja Ott verfasserin aut Michael Vieth verfasserin aut Josef Weismüller verfasserin aut Elisabeth Mangold verfasserin aut Markus M Nöthen verfasserin aut Susanne Moebus verfasserin aut Michael Knapp verfasserin aut Horst Neuhaus verfasserin aut Thomas Rösch verfasserin aut Christian Ell verfasserin aut Ines Gockel verfasserin aut Johannes Schumacher verfasserin aut Anne C Böhmer verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 14(2019), 12, p e0227072 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:14 year:2019 number:12, p e0227072 https://doi.org/10.1371/journal.pone.0227072 kostenfrei https://doaj.org/article/9c36f8077f394aafb298ab13e918fae3 kostenfrei https://doi.org/10.1371/journal.pone.0227072 kostenfrei https://doaj.org/toc/1932-6203 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_34 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_235 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2019 12, p e0227072 |
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Julia Schröder @@aut@@ Vitalia Schüller @@aut@@ Andrea May @@aut@@ Christian Gerges @@aut@@ Mario Anders @@aut@@ Jessica Becker @@aut@@ Timo Hess @@aut@@ Nicole Kreuser @@aut@@ René Thieme @@aut@@ Kerstin U Ludwig @@aut@@ Tania Noder @@aut@@ Marino Venerito @@aut@@ Lothar Veits @@aut@@ Thomas Schmidt @@aut@@ Claudia Fuchs @@aut@@ Jakob R Izbicki @@aut@@ Arnulf H Hölscher @@aut@@ Dani Dakkak @@aut@@ Boris Jansen-Winkeln @@aut@@ Yusef Moulla @@aut@@ Orestis Lyros @@aut@@ Stefan Niebisch @@aut@@ Matthias Mehdorn @@aut@@ Hauke Lang @@aut@@ Dietmar Lorenz @@aut@@ Brigitte Schumacher @@aut@@ Rupert Mayershofer @@aut@@ Yogesh Vashist @@aut@@ Katja Ott @@aut@@ Michael Vieth @@aut@@ Josef Weismüller @@aut@@ Elisabeth Mangold @@aut@@ Markus M Nöthen @@aut@@ Susanne Moebus @@aut@@ Michael Knapp @@aut@@ Horst Neuhaus @@aut@@ Thomas Rösch @@aut@@ Christian Ell @@aut@@ Ines Gockel @@aut@@ Johannes Schumacher @@aut@@ Anne C Böhmer @@aut@@ |
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Julia Schröder |
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Julia Schröder misc Medicine misc R misc Science misc Q Identification of loci of functional relevance to Barrett's esophagus and esophageal adenocarcinoma: Cross-referencing of expression quantitative trait loci data from disease-relevant tissues with genetic association data. |
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Identification of loci of functional relevance to Barrett's esophagus and esophageal adenocarcinoma: Cross-referencing of expression quantitative trait loci data from disease-relevant tissues with genetic association data |
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Identification of loci of functional relevance to Barrett's esophagus and esophageal adenocarcinoma: Cross-referencing of expression quantitative trait loci data from disease-relevant tissues with genetic association data. |
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Identification of loci of functional relevance to Barrett's esophagus and esophageal adenocarcinoma: Cross-referencing of expression quantitative trait loci data from disease-relevant tissues with genetic association data |
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Julia Schröder Vitalia Schüller Andrea May Christian Gerges Mario Anders Jessica Becker Timo Hess Nicole Kreuser René Thieme Kerstin U Ludwig Tania Noder Marino Venerito Lothar Veits Thomas Schmidt Claudia Fuchs Jakob R Izbicki Arnulf H Hölscher Dani Dakkak Boris Jansen-Winkeln Yusef Moulla Orestis Lyros Stefan Niebisch Matthias Mehdorn Hauke Lang Dietmar Lorenz Brigitte Schumacher Rupert Mayershofer Yogesh Vashist Katja Ott Michael Vieth Josef Weismüller Elisabeth Mangold Markus M Nöthen Susanne Moebus Michael Knapp Horst Neuhaus Thomas Rösch Christian Ell Ines Gockel Johannes Schumacher Anne C Böhmer |
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identification of loci of functional relevance to barrett's esophagus and esophageal adenocarcinoma: cross-referencing of expression quantitative trait loci data from disease-relevant tissues with genetic association data |
title_auth |
Identification of loci of functional relevance to Barrett's esophagus and esophageal adenocarcinoma: Cross-referencing of expression quantitative trait loci data from disease-relevant tissues with genetic association data. |
abstract |
Esophageal adenocarcinoma (EA) and its precancerous condition Barrett's esophagus (BE) are multifactorial diseases with rising prevalence rates in Western populations. A recent meta-analysis of genome-wide association studies (GWAS) data identified 14 BE/EA risk loci located in non-coding genomic regions. Knowledge about the impact of non-coding variation on disease pathology is incomplete and needs further investigation. The aim of the present study was (i) to identify candidate genes of functional relevance to BE/EA at known risk loci and (ii) to find novel risk loci among the suggestively associated variants through the integration of expression quantitative trait loci (eQTL) and genetic association data. eQTL data from two BE/EA-relevant tissues (esophageal mucosa and gastroesophageal junction) generated within the context of the GTEx project were cross-referenced with the GWAS meta-analysis data. Variants representing an eQTL in at least one of the two tissues were categorized into genome-wide significant loci (P < 5×10-8) and novel candidate loci (5×10-8 ≤ P ≤ 5×10-5). To follow up these novel candidate loci, a genetic association study was performed in a replication cohort comprising 1,993 cases and 967 controls followed by a combined analysis with the GWAS meta-analysis data. The cross-referencing of eQTL and genetic data yielded 2,180 variants that represented 25 loci. Among the previously reported genome-wide significant loci, 22 eQTLs were identified in esophageal mucosa and/or gastroesophageal junction tissue. The regulated genes, most of which have not been linked to BE/EA etiology so far, included C2orf43/LDAH, ZFP57, and SLC9A3. Among the novel candidate loci, replication was achieved for two variants (rs7754014, Pcombined = 3.16×10-7 and rs1540, Pcombined = 4.16×10-6) which represent eQTLs for CFDP1 and SLC22A3, respectively. In summary, the present approach identified candidate genes whose expression was regulated by risk variants in disease-relevant tissues. These findings may facilitate the elucidation of BE/EA pathophysiology. |
abstractGer |
Esophageal adenocarcinoma (EA) and its precancerous condition Barrett's esophagus (BE) are multifactorial diseases with rising prevalence rates in Western populations. A recent meta-analysis of genome-wide association studies (GWAS) data identified 14 BE/EA risk loci located in non-coding genomic regions. Knowledge about the impact of non-coding variation on disease pathology is incomplete and needs further investigation. The aim of the present study was (i) to identify candidate genes of functional relevance to BE/EA at known risk loci and (ii) to find novel risk loci among the suggestively associated variants through the integration of expression quantitative trait loci (eQTL) and genetic association data. eQTL data from two BE/EA-relevant tissues (esophageal mucosa and gastroesophageal junction) generated within the context of the GTEx project were cross-referenced with the GWAS meta-analysis data. Variants representing an eQTL in at least one of the two tissues were categorized into genome-wide significant loci (P < 5×10-8) and novel candidate loci (5×10-8 ≤ P ≤ 5×10-5). To follow up these novel candidate loci, a genetic association study was performed in a replication cohort comprising 1,993 cases and 967 controls followed by a combined analysis with the GWAS meta-analysis data. The cross-referencing of eQTL and genetic data yielded 2,180 variants that represented 25 loci. Among the previously reported genome-wide significant loci, 22 eQTLs were identified in esophageal mucosa and/or gastroesophageal junction tissue. The regulated genes, most of which have not been linked to BE/EA etiology so far, included C2orf43/LDAH, ZFP57, and SLC9A3. Among the novel candidate loci, replication was achieved for two variants (rs7754014, Pcombined = 3.16×10-7 and rs1540, Pcombined = 4.16×10-6) which represent eQTLs for CFDP1 and SLC22A3, respectively. In summary, the present approach identified candidate genes whose expression was regulated by risk variants in disease-relevant tissues. These findings may facilitate the elucidation of BE/EA pathophysiology. |
abstract_unstemmed |
Esophageal adenocarcinoma (EA) and its precancerous condition Barrett's esophagus (BE) are multifactorial diseases with rising prevalence rates in Western populations. A recent meta-analysis of genome-wide association studies (GWAS) data identified 14 BE/EA risk loci located in non-coding genomic regions. Knowledge about the impact of non-coding variation on disease pathology is incomplete and needs further investigation. The aim of the present study was (i) to identify candidate genes of functional relevance to BE/EA at known risk loci and (ii) to find novel risk loci among the suggestively associated variants through the integration of expression quantitative trait loci (eQTL) and genetic association data. eQTL data from two BE/EA-relevant tissues (esophageal mucosa and gastroesophageal junction) generated within the context of the GTEx project were cross-referenced with the GWAS meta-analysis data. Variants representing an eQTL in at least one of the two tissues were categorized into genome-wide significant loci (P < 5×10-8) and novel candidate loci (5×10-8 ≤ P ≤ 5×10-5). To follow up these novel candidate loci, a genetic association study was performed in a replication cohort comprising 1,993 cases and 967 controls followed by a combined analysis with the GWAS meta-analysis data. The cross-referencing of eQTL and genetic data yielded 2,180 variants that represented 25 loci. Among the previously reported genome-wide significant loci, 22 eQTLs were identified in esophageal mucosa and/or gastroesophageal junction tissue. The regulated genes, most of which have not been linked to BE/EA etiology so far, included C2orf43/LDAH, ZFP57, and SLC9A3. Among the novel candidate loci, replication was achieved for two variants (rs7754014, Pcombined = 3.16×10-7 and rs1540, Pcombined = 4.16×10-6) which represent eQTLs for CFDP1 and SLC22A3, respectively. In summary, the present approach identified candidate genes whose expression was regulated by risk variants in disease-relevant tissues. These findings may facilitate the elucidation of BE/EA pathophysiology. |
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12, p e0227072 |
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Identification of loci of functional relevance to Barrett's esophagus and esophageal adenocarcinoma: Cross-referencing of expression quantitative trait loci data from disease-relevant tissues with genetic association data. |
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https://doi.org/10.1371/journal.pone.0227072 https://doaj.org/article/9c36f8077f394aafb298ab13e918fae3 https://doaj.org/toc/1932-6203 |
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Vitalia Schüller Andrea May Christian Gerges Mario Anders Jessica Becker Timo Hess Nicole Kreuser René Thieme Kerstin U Ludwig Tania Noder Marino Venerito Lothar Veits Thomas Schmidt Claudia Fuchs Jakob R Izbicki Arnulf H Hölscher Dani Dakkak Boris Jansen-Winkeln Yusef Moulla Orestis Lyros Stefan Niebisch Matthias Mehdorn Hauke Lang Dietmar Lorenz Brigitte Schumacher Rupert Mayershofer Yogesh Vashist Katja Ott Michael Vieth Josef Weismüller Elisabeth Mangold Markus M Nöthen Susanne Moebus Michael Knapp Horst Neuhaus Thomas Rösch Christian Ell Ines Gockel Johannes Schumacher Anne C Böhmer |
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Vitalia Schüller Andrea May Christian Gerges Mario Anders Jessica Becker Timo Hess Nicole Kreuser René Thieme Kerstin U Ludwig Tania Noder Marino Venerito Lothar Veits Thomas Schmidt Claudia Fuchs Jakob R Izbicki Arnulf H Hölscher Dani Dakkak Boris Jansen-Winkeln Yusef Moulla Orestis Lyros Stefan Niebisch Matthias Mehdorn Hauke Lang Dietmar Lorenz Brigitte Schumacher Rupert Mayershofer Yogesh Vashist Katja Ott Michael Vieth Josef Weismüller Elisabeth Mangold Markus M Nöthen Susanne Moebus Michael Knapp Horst Neuhaus Thomas Rösch Christian Ell Ines Gockel Johannes Schumacher Anne C Böhmer |
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2024-07-04T00:11:25.042Z |
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score |
7.4008837 |