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Genome-wide associa...
Genome-wide association study of plasma levels of polychlorinated biphenyls disclose an association with the CYP2B6 gene in a population-based sample
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- Ng, Esther (författare)
- Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
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- Salihovic, Samira, 1985- (författare)
- Uppsala universitet,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab
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- Lind, P. Monica (författare)
- Uppsala universitet,Arbets- och miljömedicin
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- Mahajan, Anubha (författare)
- Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
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- Syvänen, Ann-Christine (författare)
- Uppsala universitet,Molekylär medicin,Science for Life Laboratory, SciLifeLab
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- Axelsson, Tomas (författare)
- Uppsala universitet,Molekylär medicin,Science for Life Laboratory, SciLifeLab
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- Ingelsson, Erik (författare)
- Uppsala universitet,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab
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- Lindgren, Cecilia M. (författare)
- Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
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- van Bavel, Bert, 1963- (författare)
- Örebro universitet,Institutionen för naturvetenskap och teknik,MTM
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- Morris, Andrew P. (författare)
- Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; Department of Biostatistics, University of Liverpool, Liverpool, United Kingdom
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- Lind, Lars (författare)
- Uppsala universitet,Kardiovaskulär epidemiologi
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(creator_code:org_t)
- Elsevier BV, 2015
- 2015
- Engelska.
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Ingår i: Environmental Research. - : Elsevier BV. - 0013-9351 .- 1096-0953. ; 140, s. 95-101
- Relaterad länk:
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https://doi.org/10.1...
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Ämnesord
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- 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 x 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 x 10(-12)) for PCB-118, rs4802104 (p= 1.4 x 10(-9)) for PCB-74 and rs4803413 (p=2.5 x 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. (C) 2015 The Authors. Published by Elsevier Inc.
Ämnesord
- NATURVETENSKAP -- Geovetenskap och miljövetenskap -- Miljövetenskap (hsv//swe)
- NATURAL SCIENCES -- Earth and Related Environmental Sciences -- Environmental Sciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Nyckelord
- Genome-wide association studies
- Polychlorinated biphenyls
- Cytochrome P450
- Single nucleotide polymorphisms
- Metabolism
- Pollutants
- Enviromental Science
- Miljövetenskap
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Ng, Esther
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Salihovic, Samir ...
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Lind, P. Monica
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Mahajan, Anubha
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Syvänen, Ann-Chr ...
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Axelsson, Tomas
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Ingelsson, Erik
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Lindgren, Cecili ...
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van Bavel, Bert, ...
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Morris, Andrew P ...
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Lind, Lars
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- Om ämnet
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- NATURVETENSKAP
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NATURVETENSKAP
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och Geovetenskap och ...
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och Miljövetenskap
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Medicinsk geneti ...
- Artiklar i publikationen
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Environmental Re ...
- Av lärosätet
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Örebro universitet
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Uppsala universitet