Formal Statistical Replication Analysis in Lung Cancer Genome-Wide Association Studies.

ABSTRACT: Dozens of genome-wide association studies (GWAS) have identified thousands of single nucleotide polymorphisms (SNPs) associated with lung cancer risk. However, it remains challenging to translate these findings to clinical insights. One well-known obstacle is the large amount of type I error attached to GWAS; attempted solutions such as setting a p-value threshold across multiple cohorts or looking for small meta-analysis p-values have only somewhat reduced false positive findings. In contrast, here we advocate for a statistical model-based replication analysis. We first demonstrate that a formal statistical test for the replication composite null hypothesis - i.e. that the regression coefficient of a SNP falls in the same direction in multiple cohorts simultaneously - can cu

SUBMITTER: Chang YH 

PROVIDER: S-EPMC12622082 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature