University of Oulu

Liu, S., Liu, Y., Zhang, Q. et al. Systematic identification of regulatory variants associated with cancer risk. Genome Biol 18, 194 (2017).

Systematic identification of regulatory variants associated with cancer risk

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Author: Liu, Song1; Zhang, Qin2; Wu, Jiayu1;
Organizations: 1State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Center for Bioinformatics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, 100005, China
2Biocenter Oulu, Faculty of Biochemistry and Molecular Medicine, University of Oulu, FIN-90014, Oulu, Finland
3Institute for Genomics and Systems Biology, and Department of Human Genetics, University of Chicago, Chicago, Illinois, 60637, USA
4Tempus Labs, Inc., Chicago, Illinois, 60654, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.6 MB)
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Language: English
Published: Springer Nature, 2017
Publish Date: 2021-03-08


Background: Most cancer risk-associated single nucleotide polymorphisms (SNPs) identified by genome-wide association studies (GWAS) are noncoding and it is challenging to assess their functional impacts. To systematically identify the SNPs that affect gene expression by modulating activities of distal regulatory elements, we adapt the self-transcribing active regulatory region sequencing (STARR-seq) strategy, a high-throughput technique to functionally quantify enhancer activities.

Results: From 10,673 SNPs linked with 996 cancer risk-associated SNPs identified in previous GWAS studies, we identify 575 SNPs in the fragments that positively regulate gene expression, and 758 SNPs in the fragments with negative regulatory activities. Among them, 70 variants are regulatory variants for which the two alleles confer different regulatory activities. We analyze in depth two regulatory variants—breast cancer risk SNP rs11055880 and leukemia risk-associated SNP rs12142375—and demonstrate their endogenous regulatory activities on expression of ATF7IP and PDE4B genes, respectively, using a CRISPR-Cas9 approach.

Conclusions: By identifying regulatory variants associated with cancer susceptibility and studying their molecular functions, we hope to help the interpretation of GWAS results and provide improved information for cancer risk assessment.

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Series: Genome biology
ISSN: 1474-7596
ISSN-E: 1474-760X
ISSN-L: 1474-7596
Volume: 18
Article number: 194
DOI: 10.1186/s13059-017-1322-z
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
3122 Cancers
Funding: This work was supported by the National Natural Science Foundation of China (31470069), CAMS Innovation Fund for Medical Sciences (CAMS-I2M, 2016-I2M-1-005), National Laboratory Special Fund (2060204), the Institute of Basic Medical Sciences start-up fund (20151225009) and the Thousand Young Talents Program of China (to XW).
Copyright information: © The Author(s). 2017. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.