Deep metabolic phenotyping of humans with protein-altering variants in TM6SF2 using a genome-first approach.

ABSTRACT:

Background & aim

An unbiased genome-first approach can expand the molecular understanding of specific genes in disease-agnostic biobanks for deeper phenotyping. TM6SF2 represents a good candidate for this approach due to its known association with steatotic liver disease (SLD).

Methods

We screened participants with whole-exome sequences in the Penn Medicine Biobank (PMBB, n >40,000) and the UK Biobank (UKB, n >200,000) for protein-altering variants in TM6SF2 and evaluated their association with liver phenotypes and clinical outcomes.

Results

Missense variants in TM6SF2 (E167K, L156P, P216L) were associated with an increased risk of clinically diagnosed and imaging-proven steatosis, independent of the PNPLA3 I48M risk allele and hepatitis B/

SUBMITTER: Huang HYR 

PROVIDER: S-EPMC11647476 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature