A genome-wide association study of 24-hour urinary excretion of endocrine disrupting chemicals

Ubiquitous exposure to environmental endocrine disrupting chemicals (EDCs) instigates a major public health problem, but much remains unknown on the inter-individual differences in metabolism and excretion of EDCs. To examine this we performed a two-stage genome-wide association study (GWAS) for 24-...
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Autor*in:	Xueling Lu [verfasserIn] Thomas P. van der Meer [verfasserIn] Zoha Kamali [verfasserIn] Martijn van Faassen [verfasserIn] Ido P. Kema [verfasserIn] André P. van Beek [verfasserIn] Xijin Xu [verfasserIn] Xia Huo [verfasserIn] Alireza Ani [verfasserIn] Ilja M. Nolte [verfasserIn] Bruce H.R. Wolffenbuttel [verfasserIn] Jana V. van Vliet-Ostaptchouk [verfasserIn] Harold Snieder [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2024

Schlagwörter:	Endocrine disruptor Metabolism Excretion Solute carrier cytochrome P450 Genome-wide association study

Übergeordnetes Werk:	In: Environment International - Elsevier, 2019, 183(2024), Seite 108396-
Übergeordnetes Werk:	volume:183 ; year:2024 ; pages:108396-

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1016/j.envint.2023.108396

Katalog-ID:	DOAJ097406546

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520			\|a Ubiquitous exposure to environmental endocrine disrupting chemicals (EDCs) instigates a major public health problem, but much remains unknown on the inter-individual differences in metabolism and excretion of EDCs. To examine this we performed a two-stage genome-wide association study (GWAS) for 24-hour urinary excretions of four parabens, two bisphenols, and nine phthalate metabolites. Results showed five genome-wide significant (p-value < 5x10-8) and replicated single nucleotide polymorphisms (SNPs) representing four independent signals that associated with mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP) and mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP). Three of the four signals were located on chromosome 10 in a locus harboring the cytochrome P450 (CYP) genes CYP2C9, CYP2C58P, and CYP2C19 (rs117529685, pMECPP = 5.38x10-25; rs117033379, pMECPP = 1.96x10-19; rs4918798, pMECPP = 4.01x10-71; rs7895726, pMEHHP = 1.37x10-15, r2 with rs4918798 = 0.93). The other signal was on chromosome 6 close to the solute carrier (SLC) genes SLC17A1, SLC17A3, SLC17A4, and SCGN (rs1359232, pMECPP = 7.6x10-16). These four SNPs explained a substantial part (8.3 % - 9.2 %) of the variance in MECPP in the replication cohort. Bioinformatics analyses supported a likely causal role of CYP2C9 and SLC17A1 in metabolism and excretion of MECPP and MEHHP. Our results provide biological insights into mechanisms of phthalate metabolism and excretion with a likely causal role for CYP2C9 and SLC17A1.
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700	0		\|a Harold Snieder \|e verfasserin \|4 aut
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allfields	10.1016/j.envint.2023.108396 doi (DE-627)DOAJ097406546 (DE-599)DOAJ720f771540a64b6aa58d659f0998cfc4 DE-627 ger DE-627 rakwb eng GE1-350 Xueling Lu verfasserin aut A genome-wide association study of 24-hour urinary excretion of endocrine disrupting chemicals 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Ubiquitous exposure to environmental endocrine disrupting chemicals (EDCs) instigates a major public health problem, but much remains unknown on the inter-individual differences in metabolism and excretion of EDCs. To examine this we performed a two-stage genome-wide association study (GWAS) for 24-hour urinary excretions of four parabens, two bisphenols, and nine phthalate metabolites. Results showed five genome-wide significant (p-value < 5x10-8) and replicated single nucleotide polymorphisms (SNPs) representing four independent signals that associated with mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP) and mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP). Three of the four signals were located on chromosome 10 in a locus harboring the cytochrome P450 (CYP) genes CYP2C9, CYP2C58P, and CYP2C19 (rs117529685, pMECPP = 5.38x10-25; rs117033379, pMECPP = 1.96x10-19; rs4918798, pMECPP = 4.01x10-71; rs7895726, pMEHHP = 1.37x10-15, r2 with rs4918798 = 0.93). The other signal was on chromosome 6 close to the solute carrier (SLC) genes SLC17A1, SLC17A3, SLC17A4, and SCGN (rs1359232, pMECPP = 7.6x10-16). These four SNPs explained a substantial part (8.3 % - 9.2 %) of the variance in MECPP in the replication cohort. Bioinformatics analyses supported a likely causal role of CYP2C9 and SLC17A1 in metabolism and excretion of MECPP and MEHHP. Our results provide biological insights into mechanisms of phthalate metabolism and excretion with a likely causal role for CYP2C9 and SLC17A1. Endocrine disruptor Metabolism Excretion Solute carrier cytochrome P450 Genome-wide association study Environmental sciences Thomas P. van der Meer verfasserin aut Zoha Kamali verfasserin aut Martijn van Faassen verfasserin aut Ido P. Kema verfasserin aut André P. van Beek verfasserin aut Xijin Xu verfasserin aut Xia Huo verfasserin aut Alireza Ani verfasserin aut Ilja M. Nolte verfasserin aut Bruce H.R. Wolffenbuttel verfasserin aut Jana V. van Vliet-Ostaptchouk verfasserin aut Harold Snieder verfasserin aut In Environment International Elsevier, 2019 183(2024), Seite 108396- (DE-627)306580829 (DE-600)1497569-5 01604120 nnns volume:183 year:2024 pages:108396- https://doi.org/10.1016/j.envint.2023.108396 kostenfrei https://doaj.org/article/720f771540a64b6aa58d659f0998cfc4 kostenfrei http://www.sciencedirect.com/science/article/pii/S0160412023006694 kostenfrei https://doaj.org/toc/0160-4120 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_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_165 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2008 GBV_ILN_2014 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4367 GBV_ILN_4700 AR 183 2024 108396-
spelling	10.1016/j.envint.2023.108396 doi (DE-627)DOAJ097406546 (DE-599)DOAJ720f771540a64b6aa58d659f0998cfc4 DE-627 ger DE-627 rakwb eng GE1-350 Xueling Lu verfasserin aut A genome-wide association study of 24-hour urinary excretion of endocrine disrupting chemicals 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Ubiquitous exposure to environmental endocrine disrupting chemicals (EDCs) instigates a major public health problem, but much remains unknown on the inter-individual differences in metabolism and excretion of EDCs. To examine this we performed a two-stage genome-wide association study (GWAS) for 24-hour urinary excretions of four parabens, two bisphenols, and nine phthalate metabolites. Results showed five genome-wide significant (p-value < 5x10-8) and replicated single nucleotide polymorphisms (SNPs) representing four independent signals that associated with mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP) and mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP). Three of the four signals were located on chromosome 10 in a locus harboring the cytochrome P450 (CYP) genes CYP2C9, CYP2C58P, and CYP2C19 (rs117529685, pMECPP = 5.38x10-25; rs117033379, pMECPP = 1.96x10-19; rs4918798, pMECPP = 4.01x10-71; rs7895726, pMEHHP = 1.37x10-15, r2 with rs4918798 = 0.93). The other signal was on chromosome 6 close to the solute carrier (SLC) genes SLC17A1, SLC17A3, SLC17A4, and SCGN (rs1359232, pMECPP = 7.6x10-16). These four SNPs explained a substantial part (8.3 % - 9.2 %) of the variance in MECPP in the replication cohort. Bioinformatics analyses supported a likely causal role of CYP2C9 and SLC17A1 in metabolism and excretion of MECPP and MEHHP. Our results provide biological insights into mechanisms of phthalate metabolism and excretion with a likely causal role for CYP2C9 and SLC17A1. Endocrine disruptor Metabolism Excretion Solute carrier cytochrome P450 Genome-wide association study Environmental sciences Thomas P. van der Meer verfasserin aut Zoha Kamali verfasserin aut Martijn van Faassen verfasserin aut Ido P. Kema verfasserin aut André P. van Beek verfasserin aut Xijin Xu verfasserin aut Xia Huo verfasserin aut Alireza Ani verfasserin aut Ilja M. Nolte verfasserin aut Bruce H.R. Wolffenbuttel verfasserin aut Jana V. van Vliet-Ostaptchouk verfasserin aut Harold Snieder verfasserin aut In Environment International Elsevier, 2019 183(2024), Seite 108396- (DE-627)306580829 (DE-600)1497569-5 01604120 nnns volume:183 year:2024 pages:108396- https://doi.org/10.1016/j.envint.2023.108396 kostenfrei https://doaj.org/article/720f771540a64b6aa58d659f0998cfc4 kostenfrei http://www.sciencedirect.com/science/article/pii/S0160412023006694 kostenfrei https://doaj.org/toc/0160-4120 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_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_165 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2008 GBV_ILN_2014 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4367 GBV_ILN_4700 AR 183 2024 108396-
allfields_unstemmed	10.1016/j.envint.2023.108396 doi (DE-627)DOAJ097406546 (DE-599)DOAJ720f771540a64b6aa58d659f0998cfc4 DE-627 ger DE-627 rakwb eng GE1-350 Xueling Lu verfasserin aut A genome-wide association study of 24-hour urinary excretion of endocrine disrupting chemicals 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Ubiquitous exposure to environmental endocrine disrupting chemicals (EDCs) instigates a major public health problem, but much remains unknown on the inter-individual differences in metabolism and excretion of EDCs. To examine this we performed a two-stage genome-wide association study (GWAS) for 24-hour urinary excretions of four parabens, two bisphenols, and nine phthalate metabolites. Results showed five genome-wide significant (p-value < 5x10-8) and replicated single nucleotide polymorphisms (SNPs) representing four independent signals that associated with mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP) and mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP). Three of the four signals were located on chromosome 10 in a locus harboring the cytochrome P450 (CYP) genes CYP2C9, CYP2C58P, and CYP2C19 (rs117529685, pMECPP = 5.38x10-25; rs117033379, pMECPP = 1.96x10-19; rs4918798, pMECPP = 4.01x10-71; rs7895726, pMEHHP = 1.37x10-15, r2 with rs4918798 = 0.93). The other signal was on chromosome 6 close to the solute carrier (SLC) genes SLC17A1, SLC17A3, SLC17A4, and SCGN (rs1359232, pMECPP = 7.6x10-16). These four SNPs explained a substantial part (8.3 % - 9.2 %) of the variance in MECPP in the replication cohort. Bioinformatics analyses supported a likely causal role of CYP2C9 and SLC17A1 in metabolism and excretion of MECPP and MEHHP. Our results provide biological insights into mechanisms of phthalate metabolism and excretion with a likely causal role for CYP2C9 and SLC17A1. Endocrine disruptor Metabolism Excretion Solute carrier cytochrome P450 Genome-wide association study Environmental sciences Thomas P. van der Meer verfasserin aut Zoha Kamali verfasserin aut Martijn van Faassen verfasserin aut Ido P. Kema verfasserin aut André P. van Beek verfasserin aut Xijin Xu verfasserin aut Xia Huo verfasserin aut Alireza Ani verfasserin aut Ilja M. Nolte verfasserin aut Bruce H.R. Wolffenbuttel verfasserin aut Jana V. van Vliet-Ostaptchouk verfasserin aut Harold Snieder verfasserin aut In Environment International Elsevier, 2019 183(2024), Seite 108396- (DE-627)306580829 (DE-600)1497569-5 01604120 nnns volume:183 year:2024 pages:108396- https://doi.org/10.1016/j.envint.2023.108396 kostenfrei https://doaj.org/article/720f771540a64b6aa58d659f0998cfc4 kostenfrei http://www.sciencedirect.com/science/article/pii/S0160412023006694 kostenfrei https://doaj.org/toc/0160-4120 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_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_165 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2008 GBV_ILN_2014 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4367 GBV_ILN_4700 AR 183 2024 108396-
allfieldsGer	10.1016/j.envint.2023.108396 doi (DE-627)DOAJ097406546 (DE-599)DOAJ720f771540a64b6aa58d659f0998cfc4 DE-627 ger DE-627 rakwb eng GE1-350 Xueling Lu verfasserin aut A genome-wide association study of 24-hour urinary excretion of endocrine disrupting chemicals 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Ubiquitous exposure to environmental endocrine disrupting chemicals (EDCs) instigates a major public health problem, but much remains unknown on the inter-individual differences in metabolism and excretion of EDCs. To examine this we performed a two-stage genome-wide association study (GWAS) for 24-hour urinary excretions of four parabens, two bisphenols, and nine phthalate metabolites. Results showed five genome-wide significant (p-value < 5x10-8) and replicated single nucleotide polymorphisms (SNPs) representing four independent signals that associated with mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP) and mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP). Three of the four signals were located on chromosome 10 in a locus harboring the cytochrome P450 (CYP) genes CYP2C9, CYP2C58P, and CYP2C19 (rs117529685, pMECPP = 5.38x10-25; rs117033379, pMECPP = 1.96x10-19; rs4918798, pMECPP = 4.01x10-71; rs7895726, pMEHHP = 1.37x10-15, r2 with rs4918798 = 0.93). The other signal was on chromosome 6 close to the solute carrier (SLC) genes SLC17A1, SLC17A3, SLC17A4, and SCGN (rs1359232, pMECPP = 7.6x10-16). These four SNPs explained a substantial part (8.3 % - 9.2 %) of the variance in MECPP in the replication cohort. Bioinformatics analyses supported a likely causal role of CYP2C9 and SLC17A1 in metabolism and excretion of MECPP and MEHHP. Our results provide biological insights into mechanisms of phthalate metabolism and excretion with a likely causal role for CYP2C9 and SLC17A1. Endocrine disruptor Metabolism Excretion Solute carrier cytochrome P450 Genome-wide association study Environmental sciences Thomas P. van der Meer verfasserin aut Zoha Kamali verfasserin aut Martijn van Faassen verfasserin aut Ido P. Kema verfasserin aut André P. van Beek verfasserin aut Xijin Xu verfasserin aut Xia Huo verfasserin aut Alireza Ani verfasserin aut Ilja M. Nolte verfasserin aut Bruce H.R. Wolffenbuttel verfasserin aut Jana V. van Vliet-Ostaptchouk verfasserin aut Harold Snieder verfasserin aut In Environment International Elsevier, 2019 183(2024), Seite 108396- (DE-627)306580829 (DE-600)1497569-5 01604120 nnns volume:183 year:2024 pages:108396- https://doi.org/10.1016/j.envint.2023.108396 kostenfrei https://doaj.org/article/720f771540a64b6aa58d659f0998cfc4 kostenfrei http://www.sciencedirect.com/science/article/pii/S0160412023006694 kostenfrei https://doaj.org/toc/0160-4120 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_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_165 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2008 GBV_ILN_2014 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4367 GBV_ILN_4700 AR 183 2024 108396-
allfieldsSound	10.1016/j.envint.2023.108396 doi (DE-627)DOAJ097406546 (DE-599)DOAJ720f771540a64b6aa58d659f0998cfc4 DE-627 ger DE-627 rakwb eng GE1-350 Xueling Lu verfasserin aut A genome-wide association study of 24-hour urinary excretion of endocrine disrupting chemicals 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Ubiquitous exposure to environmental endocrine disrupting chemicals (EDCs) instigates a major public health problem, but much remains unknown on the inter-individual differences in metabolism and excretion of EDCs. To examine this we performed a two-stage genome-wide association study (GWAS) for 24-hour urinary excretions of four parabens, two bisphenols, and nine phthalate metabolites. Results showed five genome-wide significant (p-value < 5x10-8) and replicated single nucleotide polymorphisms (SNPs) representing four independent signals that associated with mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP) and mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP). Three of the four signals were located on chromosome 10 in a locus harboring the cytochrome P450 (CYP) genes CYP2C9, CYP2C58P, and CYP2C19 (rs117529685, pMECPP = 5.38x10-25; rs117033379, pMECPP = 1.96x10-19; rs4918798, pMECPP = 4.01x10-71; rs7895726, pMEHHP = 1.37x10-15, r2 with rs4918798 = 0.93). The other signal was on chromosome 6 close to the solute carrier (SLC) genes SLC17A1, SLC17A3, SLC17A4, and SCGN (rs1359232, pMECPP = 7.6x10-16). These four SNPs explained a substantial part (8.3 % - 9.2 %) of the variance in MECPP in the replication cohort. Bioinformatics analyses supported a likely causal role of CYP2C9 and SLC17A1 in metabolism and excretion of MECPP and MEHHP. Our results provide biological insights into mechanisms of phthalate metabolism and excretion with a likely causal role for CYP2C9 and SLC17A1. Endocrine disruptor Metabolism Excretion Solute carrier cytochrome P450 Genome-wide association study Environmental sciences Thomas P. van der Meer verfasserin aut Zoha Kamali verfasserin aut Martijn van Faassen verfasserin aut Ido P. Kema verfasserin aut André P. van Beek verfasserin aut Xijin Xu verfasserin aut Xia Huo verfasserin aut Alireza Ani verfasserin aut Ilja M. Nolte verfasserin aut Bruce H.R. Wolffenbuttel verfasserin aut Jana V. van Vliet-Ostaptchouk verfasserin aut Harold Snieder verfasserin aut In Environment International Elsevier, 2019 183(2024), Seite 108396- (DE-627)306580829 (DE-600)1497569-5 01604120 nnns volume:183 year:2024 pages:108396- https://doi.org/10.1016/j.envint.2023.108396 kostenfrei https://doaj.org/article/720f771540a64b6aa58d659f0998cfc4 kostenfrei http://www.sciencedirect.com/science/article/pii/S0160412023006694 kostenfrei https://doaj.org/toc/0160-4120 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_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_165 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2008 GBV_ILN_2014 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4367 GBV_ILN_4700 AR 183 2024 108396-
language	English
source	In Environment International 183(2024), Seite 108396- volume:183 year:2024 pages:108396-
sourceStr	In Environment International 183(2024), Seite 108396- volume:183 year:2024 pages:108396-
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Endocrine disruptor Metabolism Excretion Solute carrier cytochrome P450 Genome-wide association study Environmental sciences
isfreeaccess_bool	true
container_title	Environment International
authorswithroles_txt_mv	Xueling Lu @@aut@@ Thomas P. van der Meer @@aut@@ Zoha Kamali @@aut@@ Martijn van Faassen @@aut@@ Ido P. Kema @@aut@@ André P. van Beek @@aut@@ Xijin Xu @@aut@@ Xia Huo @@aut@@ Alireza Ani @@aut@@ Ilja M. Nolte @@aut@@ Bruce H.R. Wolffenbuttel @@aut@@ Jana V. van Vliet-Ostaptchouk @@aut@@ Harold Snieder @@aut@@
publishDateDaySort_date	2024-01-01T00:00:00Z
hierarchy_top_id	306580829
id	DOAJ097406546
language_de	englisch
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callnumber-first	G - Geography, Anthropology, Recreation
author	Xueling Lu
spellingShingle	Xueling Lu misc GE1-350 misc Endocrine disruptor misc Metabolism misc Excretion misc Solute carrier misc cytochrome P450 misc Genome-wide association study misc Environmental sciences A genome-wide association study of 24-hour urinary excretion of endocrine disrupting chemicals
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topic_title	GE1-350 A genome-wide association study of 24-hour urinary excretion of endocrine disrupting chemicals Endocrine disruptor Metabolism Excretion Solute carrier cytochrome P450 Genome-wide association study
topic	misc GE1-350 misc Endocrine disruptor misc Metabolism misc Excretion misc Solute carrier misc cytochrome P450 misc Genome-wide association study misc Environmental sciences
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title	A genome-wide association study of 24-hour urinary excretion of endocrine disrupting chemicals
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title_full	A genome-wide association study of 24-hour urinary excretion of endocrine disrupting chemicals
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author_browse	Xueling Lu Thomas P. van der Meer Zoha Kamali Martijn van Faassen Ido P. Kema André P. van Beek Xijin Xu Xia Huo Alireza Ani Ilja M. Nolte Bruce H.R. Wolffenbuttel Jana V. van Vliet-Ostaptchouk Harold Snieder
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title_sort	genome-wide association study of 24-hour urinary excretion of endocrine disrupting chemicals
callnumber	GE1-350
title_auth	A genome-wide association study of 24-hour urinary excretion of endocrine disrupting chemicals
abstract	Ubiquitous exposure to environmental endocrine disrupting chemicals (EDCs) instigates a major public health problem, but much remains unknown on the inter-individual differences in metabolism and excretion of EDCs. To examine this we performed a two-stage genome-wide association study (GWAS) for 24-hour urinary excretions of four parabens, two bisphenols, and nine phthalate metabolites. Results showed five genome-wide significant (p-value < 5x10-8) and replicated single nucleotide polymorphisms (SNPs) representing four independent signals that associated with mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP) and mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP). Three of the four signals were located on chromosome 10 in a locus harboring the cytochrome P450 (CYP) genes CYP2C9, CYP2C58P, and CYP2C19 (rs117529685, pMECPP = 5.38x10-25; rs117033379, pMECPP = 1.96x10-19; rs4918798, pMECPP = 4.01x10-71; rs7895726, pMEHHP = 1.37x10-15, r2 with rs4918798 = 0.93). The other signal was on chromosome 6 close to the solute carrier (SLC) genes SLC17A1, SLC17A3, SLC17A4, and SCGN (rs1359232, pMECPP = 7.6x10-16). These four SNPs explained a substantial part (8.3 % - 9.2 %) of the variance in MECPP in the replication cohort. Bioinformatics analyses supported a likely causal role of CYP2C9 and SLC17A1 in metabolism and excretion of MECPP and MEHHP. Our results provide biological insights into mechanisms of phthalate metabolism and excretion with a likely causal role for CYP2C9 and SLC17A1.
abstractGer	Ubiquitous exposure to environmental endocrine disrupting chemicals (EDCs) instigates a major public health problem, but much remains unknown on the inter-individual differences in metabolism and excretion of EDCs. To examine this we performed a two-stage genome-wide association study (GWAS) for 24-hour urinary excretions of four parabens, two bisphenols, and nine phthalate metabolites. Results showed five genome-wide significant (p-value < 5x10-8) and replicated single nucleotide polymorphisms (SNPs) representing four independent signals that associated with mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP) and mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP). Three of the four signals were located on chromosome 10 in a locus harboring the cytochrome P450 (CYP) genes CYP2C9, CYP2C58P, and CYP2C19 (rs117529685, pMECPP = 5.38x10-25; rs117033379, pMECPP = 1.96x10-19; rs4918798, pMECPP = 4.01x10-71; rs7895726, pMEHHP = 1.37x10-15, r2 with rs4918798 = 0.93). The other signal was on chromosome 6 close to the solute carrier (SLC) genes SLC17A1, SLC17A3, SLC17A4, and SCGN (rs1359232, pMECPP = 7.6x10-16). These four SNPs explained a substantial part (8.3 % - 9.2 %) of the variance in MECPP in the replication cohort. Bioinformatics analyses supported a likely causal role of CYP2C9 and SLC17A1 in metabolism and excretion of MECPP and MEHHP. Our results provide biological insights into mechanisms of phthalate metabolism and excretion with a likely causal role for CYP2C9 and SLC17A1.
abstract_unstemmed	Ubiquitous exposure to environmental endocrine disrupting chemicals (EDCs) instigates a major public health problem, but much remains unknown on the inter-individual differences in metabolism and excretion of EDCs. To examine this we performed a two-stage genome-wide association study (GWAS) for 24-hour urinary excretions of four parabens, two bisphenols, and nine phthalate metabolites. Results showed five genome-wide significant (p-value < 5x10-8) and replicated single nucleotide polymorphisms (SNPs) representing four independent signals that associated with mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP) and mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP). Three of the four signals were located on chromosome 10 in a locus harboring the cytochrome P450 (CYP) genes CYP2C9, CYP2C58P, and CYP2C19 (rs117529685, pMECPP = 5.38x10-25; rs117033379, pMECPP = 1.96x10-19; rs4918798, pMECPP = 4.01x10-71; rs7895726, pMEHHP = 1.37x10-15, r2 with rs4918798 = 0.93). The other signal was on chromosome 6 close to the solute carrier (SLC) genes SLC17A1, SLC17A3, SLC17A4, and SCGN (rs1359232, pMECPP = 7.6x10-16). These four SNPs explained a substantial part (8.3 % - 9.2 %) of the variance in MECPP in the replication cohort. Bioinformatics analyses supported a likely causal role of CYP2C9 and SLC17A1 in metabolism and excretion of MECPP and MEHHP. Our results provide biological insights into mechanisms of phthalate metabolism and excretion with a likely causal role for CYP2C9 and SLC17A1.
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title_short	A genome-wide association study of 24-hour urinary excretion of endocrine disrupting chemicals
url	https://doi.org/10.1016/j.envint.2023.108396 https://doaj.org/article/720f771540a64b6aa58d659f0998cfc4 http://www.sciencedirect.com/science/article/pii/S0160412023006694 https://doaj.org/toc/0160-4120
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author2Str	Thomas P. van der Meer Zoha Kamali Martijn van Faassen Ido P. Kema André P. van Beek Xijin Xu Xia Huo Alireza Ani Ilja M. Nolte Bruce H.R. Wolffenbuttel Jana V. van Vliet-Ostaptchouk Harold Snieder
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A genome-wide association study of 24-hour urinary excretion of endocrine disrupting chemicals

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