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Reposted by Dr Gareth Hawkes

Tim Frayling @timfrayling.bsky.social · May 27

Already-risen Exeter star Gareth Hawkes @drghawkes.bsky.social following up with the latest master class in how to use WGS data, >1 billion variant based GWAS. They bypassed the WES era as didn't want to leave out 99% of the genome :-) #ESHG2025

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Dr Gareth Hawkes @drghawkes.bsky.social · May 27

Come along today and see me and Harry begin to tackle the exponentially increasing population scale WGS data! #ESHG2025 #ESHG25

Caroline Wright @carolinefwright.bsky.social · May 27

Last day of #ESHG25 #ESHG2025, make sure to catch two fantastic back-to-back talks from @hls.exeter.ac.uk @drghawkes.bsky.social describing whole genome association analysis and meta-analysis across >500,000 people (Tuesday 11:15 & 11:30, C32)

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Reposted by Dr Gareth Hawkes

Kartik Chundru @chundru.bsky.social · May 26

I will be talking today in Space 3. The session starts at 10:30, my talk will be at 11:15
Come join if you are interested in de novo mutations, non-coding genome, rare disease, or just up for seeing @nickywhiffin.bsky.social talk about RNU4-2 saturation mutagenesis after me 😂
#ESHG2025

Dr Gareth Hawkes @drghawkes.bsky.social · May 23

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

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Dr Gareth Hawkes @drghawkes.bsky.social · May 23

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

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Reposted by Dr Gareth Hawkes

Jeff Spence @jeffspence.github.io · Mar 28

A really nice paper by @drghawkes.bsky.social et al. argues that rare and common genetic associations converge on the same genes.

While this seems at odds with our recent work about how burden tests and GWAS prioritize different genes, our results agree (🧬🧪🧵 1/6)

www.biorxiv.org/content/10.1...

Whole-genome sequencing analysis of anthropometric traits in 672,976 individuals reveals convergence between rare and common genetic associations

Genetic association studies have mostly focussed on common variants from genotyping arrays or rare protein-coding variants from exome sequencing. Here, we used whole-genome sequence (WGS) data in 672,...

www.biorxiv.org

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Dr Gareth Hawkes @drghawkes.bsky.social · Mar 24

Excited to be able to announce I’ll be starting a 5-year MRC Career Development Award fellowship next week on the 1st April at the University of Exeter! Lots of work to do on whole genomes, and I’m hoping to keep contributing my small piece!

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Dr Gareth Hawkes @drghawkes.bsky.social · Mar 14

Last few days to apply! @exeter.ac.uk

Dr Gareth Hawkes @drghawkes.bsky.social · Feb 18

We’re hiring! Looking for a motivated data scientist/bio-informatician to join our team analysing WGS across biobanks via meta analysis, with a focus on T2D and its related traits. Please get in touch if you’re interested!
tinyurl.com/3wdfc2me

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Reposted by Dr Gareth Hawkes

Tim Frayling @timfrayling.bsky.social · Feb 21

Interested in a PhD & have strong computational skills ? Study diabetes & heart disease using peta bytes of human genetic & medical record data. In a lovely central European location and as part of a cohort of Genomics and Digital Health students : lifesciencesphd.unige.ch/jobs

University of Geneva - PhD School of Life Sciences | Jobs

Open positions in the wold of life sciences. All you need to organize you scientific life is there! Do not miss them!

lifesciencesphd.unige.ch

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Reposted by Dr Gareth Hawkes

Cedric Boeckx @cedricboeckx.bsky.social · Feb 26

Very interesting finding in this study led by @drghawkes.bsky.social: convergence between rare and common genetic associations. Implications for the genetic architecture of complex traits 🧪🧬
www.biorxiv.org/content/10.1...

www.biorxiv.org

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Reposted by Dr Gareth Hawkes

Sasha Gusev @sashagusevposts.bsky.social · Feb 26

We finally have some well-powered whole-genome heritability estimates, including a quasi-behavioral trait (BMI). For height, ~89% of the heritability estimated to reside in common variants. For BMI and WHR, ~100% estimated in common variants.

www.biorxiv.org/content/10.1...

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Reposted by Dr Gareth Hawkes

Mike Inouye @mikeinouye.bsky.social · Feb 25

Exeter doing some great stuff with biobank scale WGS at the moment!

Whole-genome sequencing analysis of anthropometric traits in 672,976 individuals reveals convergence between rare and common genetic associations www.biorxiv.org/content/10.1...

Whole-genome sequencing analysis of anthropometric traits in 672,976 individuals reveals convergence between rare and common genetic associations

Genetic association studies have mostly focussed on common variants from genotyping arrays or rare protein-coding variants from exome sequencing. Here, we used whole-genome sequence (WGS) data in 672,...

www.biorxiv.org

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Dr Gareth Hawkes @drghawkes.bsky.social · Feb 26

Also want to specifically call out our rising-star Early Career Researcher (who isn't on bluesky/twitter!) Harry Wright, who nearly single-handedly conquered the All of Us data, in particular the WGS VDS format: more from him in the near future...

@anna123.bsky.social @timfrayling.bsky.social

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Dr Gareth Hawkes @drghawkes.bsky.social · Feb 26

This was a really fun and exciting project to work on, and hopefully shows we're not near to exhausting population-scale WGS data. A great collaboration led by @mnweedon.bsky.social @drarwood.bsky.social and @carolinefwright.bsky.social , with @chundru.bsky.social and @rnbeaumont.bsky.social

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Dr Gareth Hawkes @drghawkes.bsky.social · Feb 26

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

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Dr Gareth Hawkes @drghawkes.bsky.social · Feb 26

We also identify another example of a gene-phenotype association only identified by aggregation of rare non-coding variants via WGS: 5-prime UTR variants in FGF18 were associated with up to 6cm difference in height, but we observed no coding association (possibly due to strong coding constraint)

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Dr Gareth Hawkes @drghawkes.bsky.social · Feb 26

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

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Dr Gareth Hawkes @drghawkes.bsky.social · Feb 26

We then assessed the heritability of rare variants (MAF>0.01%) using RHE-mc regression in UKB. We found a notable contribution for height (~11%), which almost entirely co-localised with common variants, but little to no evidence of rare-variant heritability for BMI and WHRadjBMI

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Dr Gareth Hawkes @drghawkes.bsky.social · Feb 26

Based on our discovery-replication framework, 97% of our rare-variant findings co-localised with previously reported common variation.

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Dr Gareth Hawkes @drghawkes.bsky.social · Feb 26

Really excited to share our next population-scale WGS work preprint. Here, we analyse three anthropometric traits in nearly 700,000 individuals (discovery UKB ~450K, replication AoU). We show, for these traits, that common and rare variant heritability is convergent

www.biorxiv.org/content/10.1...

Whole-genome sequencing analysis of anthropometric traits in 672,976 individuals reveals convergence between rare and common genetic associations

Genetic association studies have mostly focussed on common variants from genotyping arrays or rare protein-coding variants from exome sequencing. Here, we used whole-genome sequence (WGS) data in 672,...

www.biorxiv.org

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Dr Gareth Hawkes @drghawkes.bsky.social · Feb 24

@chundru.bsky.social @drarwood.bsky.social @anna123.bsky.social @exeter.ac.uk

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Dr Gareth Hawkes @drghawkes.bsky.social · Feb 24

I believe our work demonstrates that the non-coding genome is rife for biological discovery: the exome doesn't have it all! A great collaborative work at Exeter with lots of my amazing colleagues @mnweedon.bsky.social @carolinefwright.bsky.social @rnbeaumont.bsky.social @timfrayling.bsky.social

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Dr Gareth Hawkes @drghawkes.bsky.social · Feb 24

And finally, we demonstrate that our findings were enriched for regulatory regions active in liver (where many proteins are manufactured) and blood (where the proteins were measured), suggesting they represent truly tissue-specific regulatory effects

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Dr Gareth Hawkes @drghawkes.bsky.social · Feb 24

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

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Dr Gareth Hawkes @drghawkes.bsky.social · Feb 24

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

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Dr Gareth Hawkes @drghawkes.bsky.social · Feb 24

We show that it is possible to aggregate rare non-coding variants in a manner akin to coding variants, and that this approach results in findings above and beyond single variant testing alone: 21% (/357) of our non-coding aggregates contained no single-independent variant

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