Some exciting openings in Exeter for clinical academics (professor and senior lecturer). Come and shape the future of translational genomic medical research in the South West! Lovely place to work, lovely people to work with, and freedom to pursue great science... www.linkedin.com/jobs/view/43...

Excited to share my first preprint on federated conditional analysis of rare single variant and aggregate association tests across six genetically-inferred ancestry groups in All of Us and UK Biobank doi.org/10.64898/202...

Federated cross-biobank conditional analysis identifies LDL-C lowering effects of DNAJC13 haploinsufficiency and LDLR regulation www.biorxiv.org/content/10.64898/2026.02...

I'm now hearing that the pause at BBSRC might last a while year. This is absolutely devastating for British biology. The number of young postdocs while will be lost to science is innumerable.

I've now heard (fourth hand) that members of boards have been told that they should only consider 15 applications at the next board, and that they should only recommend 3 for award. These boards receive over 100 applications, and would usually be expected to award around 15! So that's 1/5 of normal!

I'm seeing relatively little chatter or outcry about what is happening at the MRC, the UK's biomedical research funder.

Before Christmas MRC paused the acceptance of many of its grants, including the standard applicant-led research grant. There has been no public information on what is happening 🧵

Please forward this to any you know who could be interested!

The incredible @drghawkes.bsky.social will be leading a course on analysis of genome sequence data, functional annotation of the genome, and using the very, very exciting AlphaGenome tool

If you are looking to learn about rare variant WGS analyses, AlphaGenome and lots more, come join us in Exeter next September. It’s going to be a great few days!

Genomic superstar @chundru.bsky.social taking on fake-news genotypes in >900k individuals. He shows allele-level filtering is rarely suffifient, and makes the brave choice to properly tackle chrX!

We’ll be providing our filtered AoU WGS plink pgens for all registered users: watch this space

Genotype-level quality control substantially reduces error rates in population-scale whole-genome sequencing Population-scale whole-genome sequencing data will contain many individual-level genotype errors, even after allele-level quality control (QC). We establish the need for genotype-level QC using UK Bio...

New paper on everyone’s favourite topic, QC!
We show why you should do genotype-level QC on your WGS data

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

Very real quotes about this paper -
“The most exciting, mind-blowing paper of the year!”
“On a par with Fisher 1918”
“I read it every night. Just so beautiful”

Thank you to other co-authors @carolinefwright.bsky.social, @mnweedon.bsky.social, @timfrayling.bsky.social, and @drarwood.bsky.social, @nihrexeterbrc.bsky.social, biobanks @ukbiobank.bsky.social and All of Us, and all of the participants of the studies

Population prevalence, penetrance, and mortality for genetically confirmed MODY AbstractContext. Diagnosing Maturity-Onset Diabetes of the Young (MODY) is clinically important for treatment and prognosis. However, phenotype-based studi

Excited to announce the acceptance and publication of our paper titled “Population prevalence, penetrants, and mortality for genetically confirmed MODY” in JCEM: doi.org/10.1210/clin...
#MODY #monogenicdiabetes

Population prevalence, penetrance, and mortality for genetically confirmed MODY AbstractContext. Diagnosing Maturity-Onset Diabetes of the Young (MODY) is clinically important for treatment and prognosis. However, phenotype-based studi

Population prevalence, penetrance, and mortality for genetically confirmed MODY: academic.oup.com/jcem/article...

Excellent autumnal away-day by the seaside with the Exeter genomics teams, organised by @drghawkes.bsky.social, discussing improvements to our whole genome sequence annotation and burden-testing pipelines - lots more exciting science to come! @exeter.ac.uk @nihrexeterbrc.bsky.social

🎉 New preprint out!

"Removing genetic effects on plasma proteins enhances their utility as disease biomarkers"

We show that adjusting plasma proteins for genetic effects can make them stronger predictors of disease

👉 doi.org/10.1101/2025...

Common genetic variants modify disease risk and clinical presentation in monogenic diabetes - Nature Metabolism In clinical and population-based cohorts, a strong contribution of polygenic risk for type 2 diabetes (T2D) significantly modifies the onset and phenotypic variability of maturity-onset diabetes of the young (MODY). This polygenic T2D burden may also account for MODY-like individuals without identified monogenic causes.

RESEARCH | J Murray Leech, KA Patel et al.
@exeter.ac.uk

Polygenic risk for T2D modifies the onset and phenotypic variability of maturity-onset diabetes of the young (MODY) 🧪

The minor spliceosome is a master immune regulator Pathogenic variants in non-coding genes are emerging as critical contributors to human rare diseases. We identified 19 individuals with early-onset diabetes (diagnosed <5 years) and additional clinica...

I’m excited to share the 2 newest Neonatal diabetes genes: RNU4ATAC and RNU6ATAC. These genes encode snRNA components of the minor spliceosome and biallelic variants in them cause monogenic autoimmune diabetes. If you are at #EASD, come to Matt Johnson’s talk Tuesday @4pm in Milan hall to hear more.

Common genetic variants modify disease risk and clinical presentation in monogenic diabetes - Nature Metabolism In clinical and population-based cohorts, a strong contribution of polygenic risk for type 2 diabetes (T2D) significantly modifies the onset and phenotypic variability of maturity-onset diabetes of th...

Now out in @natmetabolism.nature.com! Excited to share our work showing how common genetic changes shape how diabetes presents in MODY (Maturity-Onset Diabetes of the Young). Our findings highlight the growing overlap between monogenic and polygenic forms of diabetes.

www.nature.com/articles/s42...

Rare Variants in NEUROD1 and PDX1 Are Low-Penetrance Causes of MODY, Whereas Those in APPL1 and WFS1 Are Not Associated With MODY An accurate genetic diagnosis of maturity-onset diabetes of the young (MODY) is critical for personalized treatment. To avoid misdiagnosis, only genes with

Our paper is now out on Diabetes!
diabetesjournals.org/diabetes/art...

New preprint out now! We show polygenic background shapes GCK-MODY clinical presentation. In >1,000 cases, higher polygenic risk increased the chance of exceeding diagnostic diabetes thresholds, highlighting how monogenic & polygenic factors jointly shape disease. #Genetics

🚨 Our parent-of-origin study is out in Nature! 🧬
Maternal and paternal alleles can have distinct — even opposite — effects on human traits, revealing a hidden layer of genetic architecture that standard GWAS miss.
🔗 www.nature.com/articles/s41...

Highlights below!

Development and recalibration of a multivariable type 1 diabetes prediction model for type 1 diabetes across multiple screening studies - BMC Medicine Background Accurate type 1 diabetes prediction is important to facilitate screening for pre-clinical type 1 diabetes to enable potential early disease-modifying interventions and to reduce the risk of...

🚨Big news! Excited to share my first PhD paper!🎉
We validated & improved a T1D risk model using TrialNet data (originally from TEDDY), boosting accuracy 📈
bmcmedicine.biomedcentral.com/articles/10....
Try the web tool 👉 t1dpredictor.diabetesgenes.org
#T1D #RiskPrediction #PrecisionMedicine #TrialNet

Non-autoimmune, insulin-deficient diabetes in children and young adults in Africa: evidence from the Young-Onset Diabetes in sub-Saharan Africa (YODA) cross-sectional study In sub-Saharan Africa, clinically diagnosed type 1 diabetes is heterogeneous, comprising classic autoimmune type 1 diabetes and a novel, non-autoimmune, insulin-deficient diabetes subtype. There is ev...

New Research:
Non-autoimmune, insulin-deficient #diabetes in children and young adults in #Africa: evidence from the Young-Onset Diabetes in sub-Saharan Africa (YODA) cross-sectional study thelancet.com/journals/lan... #T1D
#OpenAccess

#MedSky #EndoSky

Complete Loss of PAX4 causes Transient Neonatal Diabetes in Humans Gene discovery studies in individuals with diabetes diagnosed within 6 months of life (neonatal diabetes, NDM) can provide unique insights into the de…

Really proud of this Exeter–Stanford collaboration identifying bi-allelic variants in PAX4 as a novel cause of transient neonatal diabetes—the first new genetic cause of this subtype described in over a decade. This work expands our understanding of beta cell development.
🔗 doi.org/10.1016/j.mo...

Population prevalence, penetrance, and mortality for genetically confirmed MODY www.medrxiv.org/content/10.1101/2025.06....

Lausanne Comp Bio Symposium 2025 (cbiosymposium.unil.ch)

🗓 Abstract deadline 30 June (𝟑 𝐝𝐚𝐲𝐬 𝐭𝐨 𝐠𝐨!!!)
🎤 Oral presentation notifications: 7 July
✅ Early Bird registration deadline: 11 July
💰 Registration fee for non-PI: 150 CHF

MODY is prevalent in later onset diabetes. Really proud to announce the release of a preprint of our paper assessing MODY in people diagnosed with diabetes later in life!!
#MonogenicDiabetes

Out today from #HectorOrtega & #SethASharp A state of the art review on polygenic risk scores (#PRS) in diabetes. This is your #101 on what we currently know about them and their application to understanding disease heterogeneity & clinical translation.

Read for free here - rdcu.be/eprel

Excited to share the preprint of our paper (my first paper!) looking at limited evidence MODY genes. We use rare variant burden testing and one of the largest MODY cohorts to evaluate the pathogenicity of these genes. This evidence can help inform clinical guidelines in MODY genetic testing!