Abstract 287: Characterizing the genetic basis of methylome diversity in histologically normal human lung tissue

Autor: Paula L. Hyland, Ben P. Berman, Jing Huang, Zea Borok, Po-Han Chen, Mathew Freedman, Zhaoming Wang, Margaret A. Tucker, Diane Lee, Jianxin Shi, Timothy J. Triche, Maria Teresa Landi, Jubao Duan, Kim Siegmund, Ite A. Laird-Offringa, Andrew C. Warner, Mihaela Campan, Peng Li, Nilanjan Chatterjee, Laufey T. Amundadottir, Weiyin Zhou, Angela Cecilia Pesatori, Pier Alberto Bertazzi, William Wheeler, Amy Hutchinson, Neil E. Caporaso, Dario Consonni, Beiyun Zhou, Andrew W. Bergen, Stephen J. Chanock, Brian Chung, Crystal N. Marconett
Rok vydání: 2014
Předmět:
Zdroj: Cancer Research. 74:287-287
ISSN: 1538-7445
0008-5472
DOI: 10.1158/1538-7445.am2014-287
Popis: The genetic regulation of the human epigenome is not fully appreciated. Here we describe the effects of genetic variants on the DNA methylome in human lung based on methylation-quantitative trait loci (meQTL) analyses. We report 34,304 cis- and 585 trans-meQTLs, a genetic-epigenetic interaction of surprising magnitude, including a regulatory hotspot. These findings are replicated in both breast and kidney tissues and show distinct patterns: cis-meQTLs mostly localize to CpG sites outside of genes, promoters, and CpG islands (CGIs) while trans-meQTLs are over-represented in promoter CGIs. meQTL SNPs are enriched in CTCF binding sites, DNaseI hypersensitivity regions and histone marks. Importantly, 4 of the 5 established lung cancer risk loci in European ancestry are cis-meQTLs and, in aggregate, cis-meQTLs are enriched for lung cancer risk in a genome-wide analysis of 11,587 subjects. Thus, inherited genetic variation may affect lung carcinogenesis by regulating the human methylome. Citation Format: Jianxin Shi, Crystal Marconett, Jubao Duan, Paula Hyland, Peng Li, Zhaoming Wang, William Wheeler, Mihaela Campan, Jing Huang, Weiyin Zhou, Tim Triche, Laufey Amundadottir, Amy Hutchinson, Po-Han Chen, Beiyun Zhou, Brian Chung, Pier Alberto Bertazzi, Andrew W. Bergen, Mathew Freedman, Diane Lee, Kim Siegmund, Andrew Clay Warner, Ben Berman, Angela C. Pesatori, Zea Borok, Dario Consonni, Nilanjan Chatterjee, Margaret Tucker, Neil Caporaso, Stephen J. Chanock, Ite A. Laird-Offringa, Maria Teresa Landi. Characterizing the genetic basis of methylome diversity in histologically normal human lung tissue. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 287. doi:10.1158/1538-7445.AM2014-287
Databáze: OpenAIRE
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