Colocalised Genetic Associations Reveal Alternative Splicing Variants as Candidate Causal Links for Breast Cancer Risk in 10 Loci.

ABSTRACT: Genome-wide association studies (GWASs) have revealed numerous loci associated with breast cancer risk, yet the precise causal variants, their impact on molecular mechanisms, and the affected genes often remain elusive. We hypothesised that specific variants exert their influence by affecting cis-regulatory alternative splice elements. An analysis of splicing quantitative trait loci (sQTL) in healthy breast tissue from female individuals identified multiple variants linked to alterations in splicing ratios. Through colocalisation analysis, we pinpointed 43 variants within twelve genes that serve as candidate causal links between sQTL and GWAS findings. In silico splice analysis highlighted a potential mechanism for three genes-FDPS, SGCE, and MRPL11-where variants in p

SUBMITTER: Besouro-Duarte A 

PROVIDER: S-EPMC11394352 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature