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Genome-wide association study of plasma levels of polychlorinated biphenyls disclose an association with the CYP2B6 gene in a population-based sample

BACKGROUND: Polychlorinated biphenyls (PCBs) are a group of man-made environmental pollutants which accumulate in humans with adverse health effects. To date, very little effort has been devoted to the study of the metabolism of PCBs on a genome-wide level. OBJECTIVES: Here, we conducted a genome-wi...

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Autores principales: Ng, Esther, Salihovic, Samira, Monica Lind, P., Mahajan, Anubha, Syvänen, Anne-Christine, Axelsson, Tomas, Ingelsson, Erik, Lindgren, Cecilia M., van Bavel, Bert, Morris, Andrew P., Lind, Lars
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Academic Press 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4509719/
https://www.ncbi.nlm.nih.gov/pubmed/25839716
http://dx.doi.org/10.1016/j.envres.2015.03.022
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author Ng, Esther
Salihovic, Samira
Monica Lind, P.
Mahajan, Anubha
Syvänen, Anne-Christine
Axelsson, Tomas
Ingelsson, Erik
Lindgren, Cecilia M.
van Bavel, Bert
Morris, Andrew P.
Lind, Lars
author_facet Ng, Esther
Salihovic, Samira
Monica Lind, P.
Mahajan, Anubha
Syvänen, Anne-Christine
Axelsson, Tomas
Ingelsson, Erik
Lindgren, Cecilia M.
van Bavel, Bert
Morris, Andrew P.
Lind, Lars
author_sort Ng, Esther
collection PubMed
description BACKGROUND: Polychlorinated biphenyls (PCBs) are a group of man-made environmental pollutants which accumulate in humans with adverse health effects. To date, very little effort has been devoted to the study of the metabolism of PCBs on a genome-wide level. OBJECTIVES: Here, we conducted a genome-wide association study (GWAS) to identify genomic regions involved in the metabolism of PCBs. METHODS: Plasma levels of 16 PCBs ascertained in a cohort of elderly individuals from Sweden (n=1016) were measured using gas chromatography–high resolution mass spectrophotometry (GC-HRMS). DNA samples were genotyped on the Infinium Omni Express bead microarray, and imputed up to reference panels from the 1000 Genomes Project. Association testing was performed in a linear regression framework under an additive model. RESULTS: Plasma levels of PCB-99 demonstrated genome-wide significant association with single nucleotide polymorphisms (SNPs) mapping to chromosome 19q13.2. The SNP with the strongest association was rs8109848 (p=3.7×10(−13)), mapping to an intronic region of CYP2B6. Moreover, when all PCBs were conditioned on PCB-99, further signals were revealed for PCBs -74, -105 and -118, mapping to the same genomic region. The lead SNPs were rs8109848 (p=3.8×10(−12)) for PCB-118, rs4802104 (p=1.4×10(−9)) for PCB-74 and rs4803413 (p=2.5×10(−9)) for PCB-105, all of which map to CYP2B6. CONCLUSIONS: In our study, we found plasma levels of four lower-chlorinated PCBs to be significantly associated with the genetic region mapping to the CYP2B6 locus. These findings show that CYP2B6 is of importance for the metabolism of PCBs in humans, and may help to identify individuals who may be susceptible to PCB toxicity.
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spelling pubmed-45097192015-08-01 Genome-wide association study of plasma levels of polychlorinated biphenyls disclose an association with the CYP2B6 gene in a population-based sample Ng, Esther Salihovic, Samira Monica Lind, P. Mahajan, Anubha Syvänen, Anne-Christine Axelsson, Tomas Ingelsson, Erik Lindgren, Cecilia M. van Bavel, Bert Morris, Andrew P. Lind, Lars Environ Res Article BACKGROUND: Polychlorinated biphenyls (PCBs) are a group of man-made environmental pollutants which accumulate in humans with adverse health effects. To date, very little effort has been devoted to the study of the metabolism of PCBs on a genome-wide level. OBJECTIVES: Here, we conducted a genome-wide association study (GWAS) to identify genomic regions involved in the metabolism of PCBs. METHODS: Plasma levels of 16 PCBs ascertained in a cohort of elderly individuals from Sweden (n=1016) were measured using gas chromatography–high resolution mass spectrophotometry (GC-HRMS). DNA samples were genotyped on the Infinium Omni Express bead microarray, and imputed up to reference panels from the 1000 Genomes Project. Association testing was performed in a linear regression framework under an additive model. RESULTS: Plasma levels of PCB-99 demonstrated genome-wide significant association with single nucleotide polymorphisms (SNPs) mapping to chromosome 19q13.2. The SNP with the strongest association was rs8109848 (p=3.7×10(−13)), mapping to an intronic region of CYP2B6. Moreover, when all PCBs were conditioned on PCB-99, further signals were revealed for PCBs -74, -105 and -118, mapping to the same genomic region. The lead SNPs were rs8109848 (p=3.8×10(−12)) for PCB-118, rs4802104 (p=1.4×10(−9)) for PCB-74 and rs4803413 (p=2.5×10(−9)) for PCB-105, all of which map to CYP2B6. CONCLUSIONS: In our study, we found plasma levels of four lower-chlorinated PCBs to be significantly associated with the genetic region mapping to the CYP2B6 locus. These findings show that CYP2B6 is of importance for the metabolism of PCBs in humans, and may help to identify individuals who may be susceptible to PCB toxicity. Academic Press 2015-07 /pmc/articles/PMC4509719/ /pubmed/25839716 http://dx.doi.org/10.1016/j.envres.2015.03.022 Text en © 2015 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ng, Esther
Salihovic, Samira
Monica Lind, P.
Mahajan, Anubha
Syvänen, Anne-Christine
Axelsson, Tomas
Ingelsson, Erik
Lindgren, Cecilia M.
van Bavel, Bert
Morris, Andrew P.
Lind, Lars
Genome-wide association study of plasma levels of polychlorinated biphenyls disclose an association with the CYP2B6 gene in a population-based sample
title Genome-wide association study of plasma levels of polychlorinated biphenyls disclose an association with the CYP2B6 gene in a population-based sample
title_full Genome-wide association study of plasma levels of polychlorinated biphenyls disclose an association with the CYP2B6 gene in a population-based sample
title_fullStr Genome-wide association study of plasma levels of polychlorinated biphenyls disclose an association with the CYP2B6 gene in a population-based sample
title_full_unstemmed Genome-wide association study of plasma levels of polychlorinated biphenyls disclose an association with the CYP2B6 gene in a population-based sample
title_short Genome-wide association study of plasma levels of polychlorinated biphenyls disclose an association with the CYP2B6 gene in a population-based sample
title_sort genome-wide association study of plasma levels of polychlorinated biphenyls disclose an association with the cyp2b6 gene in a population-based sample
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4509719/
https://www.ncbi.nlm.nih.gov/pubmed/25839716
http://dx.doi.org/10.1016/j.envres.2015.03.022
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