Large-scale whole exome sequencing studies identify two genes,CTSL and APOE, associated with lung cancer.
PLoS Genet
; 19(9): e1010902, 2023 09.
Article
em En
| MEDLINE
| ID: mdl-37738239
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pulmonares
Tipo de estudo:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
PLoS Genet
Assunto da revista:
GENETICA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Canadá