Disentangling the aetiological pathways between body mass index and site-specific cancer risk using tissue-partitioned Mendelian randomisation.

ABSTRACT:

Background

Body mass index (BMI) is known to influence the risk of various site-specific cancers, however, dissecting which subcomponents of this heterogenous risk factor are predominantly responsible for driving disease effects has proven difficult to establish. We have leveraged tissue-specific gene expression to separate the effects of distinct phenotypes underlying BMI on the risk of seven site-specific cancers.

Methods

SNP-exposure estimates were weighted in a multivariable Mendelian randomisation analysis by their evidence for colocalization with subcutaneous adipose- and brain-tissue-derived gene expression using a recently developed methodology.

Results

Our results provide evidence that brain-tissue-derived BMI variants are predominantly responsible for drivin

SUBMITTER: Leyden GM 

PROVIDER: S-EPMC9938133 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature