Trans-ethnic genome-wide meta-analysis of 35,732 cases and 34,424 controls identifies novel genomic cross-ancestry loci contributing to lung cancer susceptibility
Kyle M. Walsh,
Rowland W Pettit,
Susan M Rosenberg,
John K. Wiencke,
Maria Teresa Landi,
David C Christiani,
John K Field,
Angeline S Andrew,
Lambertius A. Kiemeney,
Matthew B Schabath,
Melinda C. Aldrich,
Rayjean J Hung,
Christopher I Amos,
Posted 07 Oct 2020
medRxiv DOI: 10.1101/2020.10.06.20207753
Posted 07 Oct 2020
Lung cancer is the leading cause of cancer death worldwide. Genome-wide association studies have revealed genetic risk factors, highlighting the role of smoking, family history, telomere regulation, and DNA damage-repair in lung cancer etiology. Many studies have focused on a single ethnic group to avoid confounding from variability in allele frequencies across populations; however, comprehensive multi-ethnic analyses may identify variants that are more likely to be causal. This large-scale, multi- ethnic meta-analyses identified 28 novel risk loci achieving genome-wide significance. Leading candidates were further studied using single-cell methods for evaluating DNA-damage. DNA-damage promoting activities were confirmed for selected genes by knockdown genes and overexpression studies.
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