Characterising cis-regulatory variation in the transcriptome of histologically normal and tumour-derived pancreatic tissues

Publication Date:
2018-02-09
Publisher:
BMJ Publishing Group
Print ISSN:
0017-5749
Electronic ISSN:
1468-3288
Topics:
Medicine
Keywords:
Gut
Published by:
http://www.bmj.com/
_version_ 1836398785185447937
autor Zhang, M., Lykke-Andersen, S., Zhu, B., Xiao, W., Hoskins, J. W., Zhang, X., Rost, L. M., Collins, I., Bunt, M. v. d., Jia, J., Parikh, H., Zhang, T., Song, L., Jermusyk, A., Chung, C. C., Zhu, B., Zhou, W., Matters, G. L., Kurtz, R. C., Yeager, M., Jensen, T. H., Brown, K. M., Ongen, H., Bamlet, W. R., Murray, B. A., McCarthy, M. I., Chanock, S. J., Chatterjee, N., Wolpin, B. M., Smith, J. P., Olson, S. H., Petersen, G. M., Shi, J., Amundadottir, L.
beschreibung Objective To elucidate the genetic architecture of gene expression in pancreatic tissues. Design We performed expression quantitative trait locus (eQTL) analysis in histologically normal pancreatic tissue samples (n=95) using RNA sequencing and the corresponding 1000 genomes imputed germline genotypes. Data from pancreatic tumour-derived tissue samples (n=115) from The Cancer Genome Atlas were included for comparison. Results We identified 38 615 cis -eQTLs (in 484 genes) in histologically normal tissues and 39 713 cis -eQTL (in 237 genes) in tumour-derived tissues (false discovery rate 〈0.1), with the strongest effects seen near transcriptional start sites. Approximately 23% and 42% of genes with significant cis -eQTLs appeared to be specific for tumour-derived and normal-derived tissues, respectively. Significant enrichment of cis -eQTL variants was noted in non-coding regulatory regions, in particular for pancreatic tissues (1.53-fold to 3.12-fold, p≤0.0001), indicating tissue-specific functional relevance. A common pancreatic cancer risk locus on 9q34.2 (rs687289) was associated with ABO expression in histologically normal (p=5.8 x 10 –8 ) and tumour-derived (p=8.3 x 10 –5 ) tissues. The high linkage disequilibrium between this variant and the O blood group generating deletion variant in ABO (exon 6) suggested that nonsense-mediated decay (NMD) of the ‘O’ mRNA might explain this finding. However, knockdown of crucial NMD regulators did not influence decay of the ABO ‘O’ mRNA, indicating that a gene regulatory element influenced by pancreatic cancer risk alleles may underlie the eQTL. Conclusions We have identified cis -eQTLs representing potential functional regulatory variants in the pancreas and generated a rich data set for further studies on gene expression and its regulation in pancreatic tissues.
citation_standardnr 6159825
datenlieferant ipn_articles
feed_id 3103
feed_publisher BMJ Publishing Group
feed_publisher_url http://www.bmj.com/
insertion_date 2018-02-09
journaleissn 1468-3288
journalissn 0017-5749
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher BMJ Publishing Group
quelle Gut
relation http://gut.bmj.com/cgi/content/short/67/3/521?rss=1
schlagwort Gut
search_space articles
shingle_author_1 Zhang, M., Lykke-Andersen, S., Zhu, B., Xiao, W., Hoskins, J. W., Zhang, X., Rost, L. M., Collins, I., Bunt, M. v. d., Jia, J., Parikh, H., Zhang, T., Song, L., Jermusyk, A., Chung, C. C., Zhu, B., Zhou, W., Matters, G. L., Kurtz, R. C., Yeager, M., Jensen, T. H., Brown, K. M., Ongen, H., Bamlet, W. R., Murray, B. A., McCarthy, M. I., Chanock, S. J., Chatterjee, N., Wolpin, B. M., Smith, J. P., Olson, S. H., Petersen, G. M., Shi, J., Amundadottir, L.
shingle_author_2 Zhang, M., Lykke-Andersen, S., Zhu, B., Xiao, W., Hoskins, J. W., Zhang, X., Rost, L. M., Collins, I., Bunt, M. v. d., Jia, J., Parikh, H., Zhang, T., Song, L., Jermusyk, A., Chung, C. C., Zhu, B., Zhou, W., Matters, G. L., Kurtz, R. C., Yeager, M., Jensen, T. H., Brown, K. M., Ongen, H., Bamlet, W. R., Murray, B. A., McCarthy, M. I., Chanock, S. J., Chatterjee, N., Wolpin, B. M., Smith, J. P., Olson, S. H., Petersen, G. M., Shi, J., Amundadottir, L.
shingle_author_3 Zhang, M., Lykke-Andersen, S., Zhu, B., Xiao, W., Hoskins, J. W., Zhang, X., Rost, L. M., Collins, I., Bunt, M. v. d., Jia, J., Parikh, H., Zhang, T., Song, L., Jermusyk, A., Chung, C. C., Zhu, B., Zhou, W., Matters, G. L., Kurtz, R. C., Yeager, M., Jensen, T. H., Brown, K. M., Ongen, H., Bamlet, W. R., Murray, B. A., McCarthy, M. I., Chanock, S. J., Chatterjee, N., Wolpin, B. M., Smith, J. P., Olson, S. H., Petersen, G. M., Shi, J., Amundadottir, L.
shingle_author_4 Zhang, M., Lykke-Andersen, S., Zhu, B., Xiao, W., Hoskins, J. W., Zhang, X., Rost, L. M., Collins, I., Bunt, M. v. d., Jia, J., Parikh, H., Zhang, T., Song, L., Jermusyk, A., Chung, C. C., Zhu, B., Zhou, W., Matters, G. L., Kurtz, R. C., Yeager, M., Jensen, T. H., Brown, K. M., Ongen, H., Bamlet, W. R., Murray, B. A., McCarthy, M. I., Chanock, S. J., Chatterjee, N., Wolpin, B. M., Smith, J. P., Olson, S. H., Petersen, G. M., Shi, J., Amundadottir, L.
shingle_catch_all_1 Characterising cis-regulatory variation in the transcriptome of histologically normal and tumour-derived pancreatic tissues
Gut
Objective To elucidate the genetic architecture of gene expression in pancreatic tissues. Design We performed expression quantitative trait locus (eQTL) analysis in histologically normal pancreatic tissue samples (n=95) using RNA sequencing and the corresponding 1000 genomes imputed germline genotypes. Data from pancreatic tumour-derived tissue samples (n=115) from The Cancer Genome Atlas were included for comparison. Results We identified 38 615 cis -eQTLs (in 484 genes) in histologically normal tissues and 39 713 cis -eQTL (in 237 genes) in tumour-derived tissues (false discovery rate <0.1), with the strongest effects seen near transcriptional start sites. Approximately 23% and 42% of genes with significant cis -eQTLs appeared to be specific for tumour-derived and normal-derived tissues, respectively. Significant enrichment of cis -eQTL variants was noted in non-coding regulatory regions, in particular for pancreatic tissues (1.53-fold to 3.12-fold, p≤0.0001), indicating tissue-specific functional relevance. A common pancreatic cancer risk locus on 9q34.2 (rs687289) was associated with ABO expression in histologically normal (p=5.8 x 10 –8 ) and tumour-derived (p=8.3 x 10 –5 ) tissues. The high linkage disequilibrium between this variant and the O blood group generating deletion variant in ABO (exon 6) suggested that nonsense-mediated decay (NMD) of the ‘O’ mRNA might explain this finding. However, knockdown of crucial NMD regulators did not influence decay of the ABO ‘O’ mRNA, indicating that a gene regulatory element influenced by pancreatic cancer risk alleles may underlie the eQTL. Conclusions We have identified cis -eQTLs representing potential functional regulatory variants in the pancreas and generated a rich data set for further studies on gene expression and its regulation in pancreatic tissues.
Zhang, M., Lykke-Andersen, S., Zhu, B., Xiao, W., Hoskins, J. W., Zhang, X., Rost, L. M., Collins, I., Bunt, M. v. d., Jia, J., Parikh, H., Zhang, T., Song, L., Jermusyk, A., Chung, C. C., Zhu, B., Zhou, W., Matters, G. L., Kurtz, R. C., Yeager, M., Jensen, T. H., Brown, K. M., Ongen, H., Bamlet, W. R., Murray, B. A., McCarthy, M. I., Chanock, S. J., Chatterjee, N., Wolpin, B. M., Smith, J. P., Olson, S. H., Petersen, G. M., Shi, J., Amundadottir, L.
BMJ Publishing Group
0017-5749
00175749
1468-3288
14683288
shingle_catch_all_2 Characterising cis-regulatory variation in the transcriptome of histologically normal and tumour-derived pancreatic tissues
Gut
Objective To elucidate the genetic architecture of gene expression in pancreatic tissues. Design We performed expression quantitative trait locus (eQTL) analysis in histologically normal pancreatic tissue samples (n=95) using RNA sequencing and the corresponding 1000 genomes imputed germline genotypes. Data from pancreatic tumour-derived tissue samples (n=115) from The Cancer Genome Atlas were included for comparison. Results We identified 38 615 cis -eQTLs (in 484 genes) in histologically normal tissues and 39 713 cis -eQTL (in 237 genes) in tumour-derived tissues (false discovery rate <0.1), with the strongest effects seen near transcriptional start sites. Approximately 23% and 42% of genes with significant cis -eQTLs appeared to be specific for tumour-derived and normal-derived tissues, respectively. Significant enrichment of cis -eQTL variants was noted in non-coding regulatory regions, in particular for pancreatic tissues (1.53-fold to 3.12-fold, p≤0.0001), indicating tissue-specific functional relevance. A common pancreatic cancer risk locus on 9q34.2 (rs687289) was associated with ABO expression in histologically normal (p=5.8 x 10 –8 ) and tumour-derived (p=8.3 x 10 –5 ) tissues. The high linkage disequilibrium between this variant and the O blood group generating deletion variant in ABO (exon 6) suggested that nonsense-mediated decay (NMD) of the ‘O’ mRNA might explain this finding. However, knockdown of crucial NMD regulators did not influence decay of the ABO ‘O’ mRNA, indicating that a gene regulatory element influenced by pancreatic cancer risk alleles may underlie the eQTL. Conclusions We have identified cis -eQTLs representing potential functional regulatory variants in the pancreas and generated a rich data set for further studies on gene expression and its regulation in pancreatic tissues.
Zhang, M., Lykke-Andersen, S., Zhu, B., Xiao, W., Hoskins, J. W., Zhang, X., Rost, L. M., Collins, I., Bunt, M. v. d., Jia, J., Parikh, H., Zhang, T., Song, L., Jermusyk, A., Chung, C. C., Zhu, B., Zhou, W., Matters, G. L., Kurtz, R. C., Yeager, M., Jensen, T. H., Brown, K. M., Ongen, H., Bamlet, W. R., Murray, B. A., McCarthy, M. I., Chanock, S. J., Chatterjee, N., Wolpin, B. M., Smith, J. P., Olson, S. H., Petersen, G. M., Shi, J., Amundadottir, L.
BMJ Publishing Group
0017-5749
00175749
1468-3288
14683288
shingle_catch_all_3 Characterising cis-regulatory variation in the transcriptome of histologically normal and tumour-derived pancreatic tissues
Gut
Objective To elucidate the genetic architecture of gene expression in pancreatic tissues. Design We performed expression quantitative trait locus (eQTL) analysis in histologically normal pancreatic tissue samples (n=95) using RNA sequencing and the corresponding 1000 genomes imputed germline genotypes. Data from pancreatic tumour-derived tissue samples (n=115) from The Cancer Genome Atlas were included for comparison. Results We identified 38 615 cis -eQTLs (in 484 genes) in histologically normal tissues and 39 713 cis -eQTL (in 237 genes) in tumour-derived tissues (false discovery rate <0.1), with the strongest effects seen near transcriptional start sites. Approximately 23% and 42% of genes with significant cis -eQTLs appeared to be specific for tumour-derived and normal-derived tissues, respectively. Significant enrichment of cis -eQTL variants was noted in non-coding regulatory regions, in particular for pancreatic tissues (1.53-fold to 3.12-fold, p≤0.0001), indicating tissue-specific functional relevance. A common pancreatic cancer risk locus on 9q34.2 (rs687289) was associated with ABO expression in histologically normal (p=5.8 x 10 –8 ) and tumour-derived (p=8.3 x 10 –5 ) tissues. The high linkage disequilibrium between this variant and the O blood group generating deletion variant in ABO (exon 6) suggested that nonsense-mediated decay (NMD) of the ‘O’ mRNA might explain this finding. However, knockdown of crucial NMD regulators did not influence decay of the ABO ‘O’ mRNA, indicating that a gene regulatory element influenced by pancreatic cancer risk alleles may underlie the eQTL. Conclusions We have identified cis -eQTLs representing potential functional regulatory variants in the pancreas and generated a rich data set for further studies on gene expression and its regulation in pancreatic tissues.
Zhang, M., Lykke-Andersen, S., Zhu, B., Xiao, W., Hoskins, J. W., Zhang, X., Rost, L. M., Collins, I., Bunt, M. v. d., Jia, J., Parikh, H., Zhang, T., Song, L., Jermusyk, A., Chung, C. C., Zhu, B., Zhou, W., Matters, G. L., Kurtz, R. C., Yeager, M., Jensen, T. H., Brown, K. M., Ongen, H., Bamlet, W. R., Murray, B. A., McCarthy, M. I., Chanock, S. J., Chatterjee, N., Wolpin, B. M., Smith, J. P., Olson, S. H., Petersen, G. M., Shi, J., Amundadottir, L.
BMJ Publishing Group
0017-5749
00175749
1468-3288
14683288
shingle_catch_all_4 Characterising cis-regulatory variation in the transcriptome of histologically normal and tumour-derived pancreatic tissues
Gut
Objective To elucidate the genetic architecture of gene expression in pancreatic tissues. Design We performed expression quantitative trait locus (eQTL) analysis in histologically normal pancreatic tissue samples (n=95) using RNA sequencing and the corresponding 1000 genomes imputed germline genotypes. Data from pancreatic tumour-derived tissue samples (n=115) from The Cancer Genome Atlas were included for comparison. Results We identified 38 615 cis -eQTLs (in 484 genes) in histologically normal tissues and 39 713 cis -eQTL (in 237 genes) in tumour-derived tissues (false discovery rate <0.1), with the strongest effects seen near transcriptional start sites. Approximately 23% and 42% of genes with significant cis -eQTLs appeared to be specific for tumour-derived and normal-derived tissues, respectively. Significant enrichment of cis -eQTL variants was noted in non-coding regulatory regions, in particular for pancreatic tissues (1.53-fold to 3.12-fold, p≤0.0001), indicating tissue-specific functional relevance. A common pancreatic cancer risk locus on 9q34.2 (rs687289) was associated with ABO expression in histologically normal (p=5.8 x 10 –8 ) and tumour-derived (p=8.3 x 10 –5 ) tissues. The high linkage disequilibrium between this variant and the O blood group generating deletion variant in ABO (exon 6) suggested that nonsense-mediated decay (NMD) of the ‘O’ mRNA might explain this finding. However, knockdown of crucial NMD regulators did not influence decay of the ABO ‘O’ mRNA, indicating that a gene regulatory element influenced by pancreatic cancer risk alleles may underlie the eQTL. Conclusions We have identified cis -eQTLs representing potential functional regulatory variants in the pancreas and generated a rich data set for further studies on gene expression and its regulation in pancreatic tissues.
Zhang, M., Lykke-Andersen, S., Zhu, B., Xiao, W., Hoskins, J. W., Zhang, X., Rost, L. M., Collins, I., Bunt, M. v. d., Jia, J., Parikh, H., Zhang, T., Song, L., Jermusyk, A., Chung, C. C., Zhu, B., Zhou, W., Matters, G. L., Kurtz, R. C., Yeager, M., Jensen, T. H., Brown, K. M., Ongen, H., Bamlet, W. R., Murray, B. A., McCarthy, M. I., Chanock, S. J., Chatterjee, N., Wolpin, B. M., Smith, J. P., Olson, S. H., Petersen, G. M., Shi, J., Amundadottir, L.
BMJ Publishing Group
0017-5749
00175749
1468-3288
14683288
shingle_title_1 Characterising cis-regulatory variation in the transcriptome of histologically normal and tumour-derived pancreatic tissues
shingle_title_2 Characterising cis-regulatory variation in the transcriptome of histologically normal and tumour-derived pancreatic tissues
shingle_title_3 Characterising cis-regulatory variation in the transcriptome of histologically normal and tumour-derived pancreatic tissues
shingle_title_4 Characterising cis-regulatory variation in the transcriptome of histologically normal and tumour-derived pancreatic tissues
timestamp 2025-06-30T23:32:35.981Z
titel Characterising cis-regulatory variation in the transcriptome of histologically normal and tumour-derived pancreatic tissues
titel_suche Characterising cis-regulatory variation in the transcriptome of histologically normal and tumour-derived pancreatic tissues
topic WW-YZ
uid ipn_articles_6159825