An Immunochip-based interaction study of contrasting interaction effects with smoking in ACPA-positive versus ACPA-negative rheumatoid arthritis
Objective. To investigate the gene–environment interaction between smoking and single nucleotide polymorphisms (SNPs), using Immunochip material, on the risk of developing either of two serologically defined subsets of RA. Methods. Interaction between smoking and 133 648 genetic markers from the Imm...
Published in: | Rheumatology |
---|---|
Main Authors: | , , , , , , , , |
Format: | Text |
Language: | English |
Published: |
Oxford University Press
2016
|
Subjects: | |
Online Access: | http://rheumatology.oxfordjournals.org/cgi/content/short/55/1/149 https://doi.org/10.1093/rheumatology/kev285 |
id |
fthighwire:oai:open-archive.highwire.org:rheumatology:55/1/149 |
---|---|
record_format |
openpolar |
spelling |
fthighwire:oai:open-archive.highwire.org:rheumatology:55/1/149 2023-05-15T17:44:56+02:00 An Immunochip-based interaction study of contrasting interaction effects with smoking in ACPA-positive versus ACPA-negative rheumatoid arthritis Jiang, Xia Källberg, Henrik Chen, Zuomei Ärlestig, Lisbeth Rantapää-Dahlqvist, Solbritt Davila, Sonia Klareskog, Lars Padyukov, Leonid Alfredsson, Lars 2016-01-01 00:00:00.0 text/html http://rheumatology.oxfordjournals.org/cgi/content/short/55/1/149 https://doi.org/10.1093/rheumatology/kev285 en eng Oxford University Press http://rheumatology.oxfordjournals.org/cgi/content/short/55/1/149 http://dx.doi.org/10.1093/rheumatology/kev285 Copyright (C) 2016, British Society for Rheumatology BASIC AND TRANSLATIONAL SCIENCE TEXT 2016 fthighwire https://doi.org/10.1093/rheumatology/kev285 2016-11-16T17:13:51Z Objective. To investigate the gene–environment interaction between smoking and single nucleotide polymorphisms (SNPs), using Immunochip material, on the risk of developing either of two serologically defined subsets of RA. Methods. Interaction between smoking and 133 648 genetic markers from the Immunochip was examined for two RA subsets, defined by the presence or absence of ACPA. A total of 1590 ACPA-positive and 891 ACPA-negative cases were compared with 1856 controls in the Swedish Epidemiological Investigation of RA (EIRA) case–control study. Logistic regression models were used to determine the presence of interaction. The proportion attributable to interaction was calculated for each smoking–SNP pair. Replication was carried out in an independent dataset from northern Sweden. To further validate and extend the results, interaction analysis was also performed using genome-wide association studies data on EIRA individuals. Results. In ACPA-positive RA, 102 SNPs interacted significantly with smoking, after Bonferroni correction. All 102 SNPs were located in the HLA region, mainly within the HLA class II region, 51 of which were replicated. No additional loci outside chromosome 6 were identified in the genome-wide association studies validation. After adjusting for HLA-DRB1 shared epitope, 15 smoking–SNP pairs remained significant for ACPA-positive RA, with 8 of these replicated (loci: BTNL2 , HLA-DRA , HLA-DRB5 , HLA-DQA1 , HLA-DOB and TAP2 ). For ACPA-negative RA, no smoking–SNP pairs passed the threshold for significance. Conclusion. Our study presents extended gene variation patterns involved in gene–smoking interaction in ACPA-positive, but not ACPA-negative, RA. Notably, variants in HLA-DRB1 and those in additional genes within the MHC class II region, but not in any other gene regions, showed interaction with smoking. Text Northern Sweden HighWire Press (Stanford University) Eira ENVELOPE(8.132,8.132,62.685,62.685) Rheumatology 55 1 149 155 |
institution |
Open Polar |
collection |
HighWire Press (Stanford University) |
op_collection_id |
fthighwire |
language |
English |
topic |
BASIC AND TRANSLATIONAL SCIENCE |
spellingShingle |
BASIC AND TRANSLATIONAL SCIENCE Jiang, Xia Källberg, Henrik Chen, Zuomei Ärlestig, Lisbeth Rantapää-Dahlqvist, Solbritt Davila, Sonia Klareskog, Lars Padyukov, Leonid Alfredsson, Lars An Immunochip-based interaction study of contrasting interaction effects with smoking in ACPA-positive versus ACPA-negative rheumatoid arthritis |
topic_facet |
BASIC AND TRANSLATIONAL SCIENCE |
description |
Objective. To investigate the gene–environment interaction between smoking and single nucleotide polymorphisms (SNPs), using Immunochip material, on the risk of developing either of two serologically defined subsets of RA. Methods. Interaction between smoking and 133 648 genetic markers from the Immunochip was examined for two RA subsets, defined by the presence or absence of ACPA. A total of 1590 ACPA-positive and 891 ACPA-negative cases were compared with 1856 controls in the Swedish Epidemiological Investigation of RA (EIRA) case–control study. Logistic regression models were used to determine the presence of interaction. The proportion attributable to interaction was calculated for each smoking–SNP pair. Replication was carried out in an independent dataset from northern Sweden. To further validate and extend the results, interaction analysis was also performed using genome-wide association studies data on EIRA individuals. Results. In ACPA-positive RA, 102 SNPs interacted significantly with smoking, after Bonferroni correction. All 102 SNPs were located in the HLA region, mainly within the HLA class II region, 51 of which were replicated. No additional loci outside chromosome 6 were identified in the genome-wide association studies validation. After adjusting for HLA-DRB1 shared epitope, 15 smoking–SNP pairs remained significant for ACPA-positive RA, with 8 of these replicated (loci: BTNL2 , HLA-DRA , HLA-DRB5 , HLA-DQA1 , HLA-DOB and TAP2 ). For ACPA-negative RA, no smoking–SNP pairs passed the threshold for significance. Conclusion. Our study presents extended gene variation patterns involved in gene–smoking interaction in ACPA-positive, but not ACPA-negative, RA. Notably, variants in HLA-DRB1 and those in additional genes within the MHC class II region, but not in any other gene regions, showed interaction with smoking. |
format |
Text |
author |
Jiang, Xia Källberg, Henrik Chen, Zuomei Ärlestig, Lisbeth Rantapää-Dahlqvist, Solbritt Davila, Sonia Klareskog, Lars Padyukov, Leonid Alfredsson, Lars |
author_facet |
Jiang, Xia Källberg, Henrik Chen, Zuomei Ärlestig, Lisbeth Rantapää-Dahlqvist, Solbritt Davila, Sonia Klareskog, Lars Padyukov, Leonid Alfredsson, Lars |
author_sort |
Jiang, Xia |
title |
An Immunochip-based interaction study of contrasting interaction effects with smoking in ACPA-positive versus ACPA-negative rheumatoid arthritis |
title_short |
An Immunochip-based interaction study of contrasting interaction effects with smoking in ACPA-positive versus ACPA-negative rheumatoid arthritis |
title_full |
An Immunochip-based interaction study of contrasting interaction effects with smoking in ACPA-positive versus ACPA-negative rheumatoid arthritis |
title_fullStr |
An Immunochip-based interaction study of contrasting interaction effects with smoking in ACPA-positive versus ACPA-negative rheumatoid arthritis |
title_full_unstemmed |
An Immunochip-based interaction study of contrasting interaction effects with smoking in ACPA-positive versus ACPA-negative rheumatoid arthritis |
title_sort |
immunochip-based interaction study of contrasting interaction effects with smoking in acpa-positive versus acpa-negative rheumatoid arthritis |
publisher |
Oxford University Press |
publishDate |
2016 |
url |
http://rheumatology.oxfordjournals.org/cgi/content/short/55/1/149 https://doi.org/10.1093/rheumatology/kev285 |
long_lat |
ENVELOPE(8.132,8.132,62.685,62.685) |
geographic |
Eira |
geographic_facet |
Eira |
genre |
Northern Sweden |
genre_facet |
Northern Sweden |
op_relation |
http://rheumatology.oxfordjournals.org/cgi/content/short/55/1/149 http://dx.doi.org/10.1093/rheumatology/kev285 |
op_rights |
Copyright (C) 2016, British Society for Rheumatology |
op_doi |
https://doi.org/10.1093/rheumatology/kev285 |
container_title |
Rheumatology |
container_volume |
55 |
container_issue |
1 |
container_start_page |
149 |
op_container_end_page |
155 |
_version_ |
1766147231937724416 |