期刊
HUMAN MOLECULAR GENETICS
卷 31, 期 R1, 页码 R22-R36出版社
OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddac140
关键词
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资金
- National Institutes of Health (NIH) [U19CA203654, R03CA25622, R01CA243483]
- Cancer Prevention Research Interest of Texas (CPRIT) award [RR170048]
This article reviews the progress of lung cancer GWAS research and emphasizes the heterogeneity of lung cancer GWAS results across histological subtypes, ancestries, and smoking status. It also highlights the importance and strategies of post-GWAS studies for lung cancer.
Fourteen years after the first genome-wide association study (GWAS) of lung cancer was published, approximately 45 genomic loci have now been significantly associated with lung cancer risk. While functional characterization was performed for several of these loci, a comprehensive summary of the current molecular understanding of lung cancer risk has been lacking. Further, many novel computational and experimental tools now became available to accelerate the functional assessment of disease-associated variants, moving beyond locus-by-locus approaches. In this review, we first highlight the heterogeneity of lung cancer GWAS findings across histological subtypes, ancestries and smoking status, which poses unique challenges to follow-up studies. We then summarize the published lung cancer post-GWAS studies for each risk-associated locus to assess the current understanding of biological mechanisms beyond the initial statistical association. We further summarize strategies for GWAS functional follow-up studies considering cutting-edge functional genomics tools and providing a catalog of available resources relevant to lung cancer. Overall, we aim to highlight the importance of integrating computational and experimental approaches to draw biological insights from the lung cancer GWAS results beyond association.
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