Gene-set meta-analysis of lung cancer identifies pathway related to systemic lupus erythematosus.
INTRODUCTION:Gene-set analysis (GSA) is an approach using the results of single-marker genome-wide association studies when investigating pathways as a whole with respect to the genetic basis of a disease. METHODS:We performed a meta-analysis of seven GSAs for lung cancer, applying the method META-G...
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doaj-a99e8a4b4cef4bffa2a719d0d87ec2aa2020-11-24T21:09:42ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01123e017333910.1371/journal.pone.0173339Gene-set meta-analysis of lung cancer identifies pathway related to systemic lupus erythematosus.Albert RosenbergerMelanie SohnsStefanie FriedrichsRayjean J HungGord FehringerJohn McLaughlinChristopher I AmosPaul BrennanAngela RischIrene BrüskeNeil E CaporasoMaria Teresa LandiDavid C ChristianiYongyue WeiHeike BickeböllerINTRODUCTION:Gene-set analysis (GSA) is an approach using the results of single-marker genome-wide association studies when investigating pathways as a whole with respect to the genetic basis of a disease. METHODS:We performed a meta-analysis of seven GSAs for lung cancer, applying the method META-GSA. Overall, the information taken from 11,365 cases and 22,505 controls from within the TRICL/ILCCO consortia was used to investigate a total of 234 pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. RESULTS:META-GSA reveals the systemic lupus erythematosus KEGG pathway hsa05322, driven by the gene region 6p21-22, as also implicated in lung cancer (p = 0.0306). This gene region is known to be associated with squamous cell lung carcinoma. The most important genes driving the significance of this pathway belong to the genomic areas HIST1-H4L, -1BN, -2BN, -H2AK, -H4K and C2/C4A/C4B. Within these areas, the markers most significantly associated with LC are rs13194781 (located within HIST12BN) and rs1270942 (located between C2 and C4A). CONCLUSIONS:We have discovered a pathway currently marked as specific to systemic lupus erythematosus as being significantly implicated in lung cancer. The gene region 6p21-22 in this pathway appears to be more extensively associated with lung cancer than previously assumed. Given wide-stretched linkage disequilibrium to the area APOM/BAG6/MSH5, there is currently simply not enough information or evidence to conclude whether the potential pleiotropy of lung cancer and systemic lupus erythematosus is spurious, biological, or mediated. Further research into this pathway and gene region will be necessary.http://europepmc.org/articles/PMC5342225?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Albert Rosenberger Melanie Sohns Stefanie Friedrichs Rayjean J Hung Gord Fehringer John McLaughlin Christopher I Amos Paul Brennan Angela Risch Irene Brüske Neil E Caporaso Maria Teresa Landi David C Christiani Yongyue Wei Heike Bickeböller |
spellingShingle |
Albert Rosenberger Melanie Sohns Stefanie Friedrichs Rayjean J Hung Gord Fehringer John McLaughlin Christopher I Amos Paul Brennan Angela Risch Irene Brüske Neil E Caporaso Maria Teresa Landi David C Christiani Yongyue Wei Heike Bickeböller Gene-set meta-analysis of lung cancer identifies pathway related to systemic lupus erythematosus. PLoS ONE |
author_facet |
Albert Rosenberger Melanie Sohns Stefanie Friedrichs Rayjean J Hung Gord Fehringer John McLaughlin Christopher I Amos Paul Brennan Angela Risch Irene Brüske Neil E Caporaso Maria Teresa Landi David C Christiani Yongyue Wei Heike Bickeböller |
author_sort |
Albert Rosenberger |
title |
Gene-set meta-analysis of lung cancer identifies pathway related to systemic lupus erythematosus. |
title_short |
Gene-set meta-analysis of lung cancer identifies pathway related to systemic lupus erythematosus. |
title_full |
Gene-set meta-analysis of lung cancer identifies pathway related to systemic lupus erythematosus. |
title_fullStr |
Gene-set meta-analysis of lung cancer identifies pathway related to systemic lupus erythematosus. |
title_full_unstemmed |
Gene-set meta-analysis of lung cancer identifies pathway related to systemic lupus erythematosus. |
title_sort |
gene-set meta-analysis of lung cancer identifies pathway related to systemic lupus erythematosus. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2017-01-01 |
description |
INTRODUCTION:Gene-set analysis (GSA) is an approach using the results of single-marker genome-wide association studies when investigating pathways as a whole with respect to the genetic basis of a disease. METHODS:We performed a meta-analysis of seven GSAs for lung cancer, applying the method META-GSA. Overall, the information taken from 11,365 cases and 22,505 controls from within the TRICL/ILCCO consortia was used to investigate a total of 234 pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. RESULTS:META-GSA reveals the systemic lupus erythematosus KEGG pathway hsa05322, driven by the gene region 6p21-22, as also implicated in lung cancer (p = 0.0306). This gene region is known to be associated with squamous cell lung carcinoma. The most important genes driving the significance of this pathway belong to the genomic areas HIST1-H4L, -1BN, -2BN, -H2AK, -H4K and C2/C4A/C4B. Within these areas, the markers most significantly associated with LC are rs13194781 (located within HIST12BN) and rs1270942 (located between C2 and C4A). CONCLUSIONS:We have discovered a pathway currently marked as specific to systemic lupus erythematosus as being significantly implicated in lung cancer. The gene region 6p21-22 in this pathway appears to be more extensively associated with lung cancer than previously assumed. Given wide-stretched linkage disequilibrium to the area APOM/BAG6/MSH5, there is currently simply not enough information or evidence to conclude whether the potential pleiotropy of lung cancer and systemic lupus erythematosus is spurious, biological, or mediated. Further research into this pathway and gene region will be necessary. |
url |
http://europepmc.org/articles/PMC5342225?pdf=render |
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