Loh Lab

Paper on repeat polymorphisms influencing glaucoma and colorectal cancer published in Cell

Ronen Mukamel and Bob Handsaker’s paper on phenotypic effects of noncoding variable number tandem repeats (VNTRs) (Mukamel*, Handsaker* et al. 2023 Cell) is now published — congratulations, Ronen and Bob! This work leveraged whole-genome sequencing data in large cohorts together with long-read assemblies from HGSVC2 to analyze 9,561 VNTRs genome-wide for effects on 786 phenotypes in UK Biobank. Highlights of association and fine-mapping results include a common intronic repeat polymorphism in TMCO1 for which the longest alleles (top 3%) confer higher glaucoma risk (OR=1.51 [1.42–1.60]) than any other common variant genome-wide, and a VNTR polymorphism downstream of EIF3H at which common repeat length variation generates a >2-fold range of colorectal cancer risk across individuals. Several other associations between VNTRs and complex traits appeared to reflect regulation of gene expression or splicing mediated by non-coding VNTRs.