Interested in whole genomes, AI and functional validation? Sign up to hear more about our summer school in the sunny southwest U.K. @exeter.ac.uk in Sept 2026, in partnership with the U.K. Functional Genomics Initiative @uk-fgx.bsky.social and Google Deepmind @nihrexeterbrc.bsky.social

Got a big showing of talented University of Exeter scientists with talks and posters at ESHG25 in Milan. Come along and find out more! @hls.exeter.ac.uk @exeter.ac.uk #ESHG25 @jamesfasham.bsky.social @jingzhan.bsky.social @ambermluckett.bsky.social @chundru.bsky.social @harrygreentkd.bsky.social

We next identify novel rare non-coding single variants not highlighted by imputation-based GWAS. For example, we identified two rare variants upstream of IGF2BP2 with large effects on WHRadjBMI, but notably different effects on adiposity traits

For height, given the common-variant saturation by Yengo et. al 2022, we further estimated heritability for ultra-rare variants (MAC>10), and found this co-localisation pattern holds, but find some remaining evidence of population stratification (or assortative mating etc) that we couldn't resolve

Rare non-coding variants had similar-magnitude effects to coding variants, but were more balanced across the frequency spectrum

Both our non-coding rare single variants and aggregates were enriched within the 5'UTR regions, suggesting they are prime (pun-intended) targets for future focused analysis

We now additionally make an important point of warning for future WGS studies: the number of 'independent' signals was correlated with WGS coverage at the protein-coding gene locus. In some cases, there is little to no coverage across coding exons, making conditional analysis impossible. E.g. CD177

Probably the best second-post on blue sky I could’ve hoped for