Large-scale whole exome sequencing studies identify two genes,CTSL and APOE, associated with lung cancer.



Xu, Jingxiong, Xu, Wei, Choi, Jiyeon, Brhane, Yonathan, Christiani, David C, Kothari, Jui, McKay, James, Field, John K ORCID: 0000-0003-3951-6365, Davies, Michael PA ORCID: 0000-0002-7609-4977, Liu, Geoffrey
et al (show 3 more authors) (2023) Large-scale whole exome sequencing studies identify two genes,CTSL and APOE, associated with lung cancer. PLoS genetics, 19 (9). e1010902-e1010902.

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Abstract

Common genetic variants associated with lung cancer have been well studied in the past decade. However, only 12.3% heritability has been explained by these variants. In this study, we investigate the contribution of rare variants (RVs) (minor allele frequency <0.01) to lung cancer through two large whole exome sequencing case-control studies. We first performed gene-based association tests using a novel Bayes Factor statistic in the International Lung Cancer Consortium, the discovery study (European, 1042 cases vs. 881 controls). The top genes identified are further assessed in the UK Biobank (European, 630 cases vs. 172 864 controls), the replication study. After controlling for the false discovery rate, we found two genes, CTSL and APOE, significantly associated with lung cancer in both studies. Single variant tests in UK Biobank identified 4 RVs (3 missense variants) in CTSL and 2 RVs (1 missense variant) in APOE stongly associated with lung cancer (OR between 2.0 and 139.0). The role of these genetic variants in the regulation of CTSL or APOE expression remains unclear. If such a role is established, this could have important therapeutic implications for lung cancer patients.

Item Type: Article
Uncontrolled Keywords: Humans, Lung Neoplasms, Apolipoproteins E, Bayes Theorem, Case-Control Studies, Exome Sequencing
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 04 Oct 2023 08:04
Last Modified: 15 Oct 2023 07:11
DOI: 10.1371/journal.pgen.1010902
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3173406