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Phenome-wide Mendelian randomisation analysis of 378,142 cases reveals risk factors for eight common cancers.

Published version
Peer-reviewed

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Abstract

For many cancers there are only a few well-established risk factors. Here, we use summary data from genome-wide association studies (GWAS) in a Mendelian randomisation (MR) phenome-wide association study (PheWAS) to identify potentially causal relationships for over 3,000 traits. Our outcome datasets comprise 378,142 cases across breast, prostate, colorectal, lung, endometrial, oesophageal, renal, and ovarian cancers, as well as 485,715 controls. We complement this analysis by systematically mining the literature space for supporting evidence. In addition to providing supporting evidence for well-established risk factors (smoking, alcohol, obesity, lack of physical activity), we also find sex steroid hormones, plasma lipids, and telomere length as determinants of cancer risk. A number of the molecular factors we identify may prove to be potential biomarkers. Our analysis, which highlights aetiological similarities and differences in common cancers, should aid public health prevention strategies to reduce cancer burden. We provide a R/Shiny app to visualise findings.

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Keywords

Male, Female, Humans, Genome-Wide Association Study, Risk Factors, Phenomics, Phenotype, Ovarian Neoplasms, Mendelian Randomization Analysis, Polymorphism, Single Nucleotide

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

15

Publisher

Springer Science and Business Media LLC