Genotype-first approach reveals monogenic lipodystrophy is underdiagnosed, with health and mortality risks Monogenic lipodystrophy is more common than currently recognised and most cases remain undiagnosed despite significant cardiometabolic and mortality risks. These findings highlight the value of genoty...

Now out in @ebiomedicine.bsky.social !!!

Excited to share our work using a genotype-first approach to assess monogenic lipodystrophy in a large population cohort highlighting the disease’s underdiagnosis and health impacts.

www.thelancet.com/journals/ebi...

Polygenic background contributes to GCK-MODY clinical presentation and glycaemic variability - Diabetologia Aims/hypothesis GCK-MODY (glucokinase MODY) causes lifelong, mild hyperglycaemia with high penetrance. Variation in glycaemic phenotype among carriers remains unexplained. We hypothesised that polygen...

In GCK-MODY, polygenic background modifies clinical presentation despite high penetrance. Polygenic risk influences who crosses key diagnostic HbA1c thresholds. Monogenic + polygenic risk both matter. #Diabetes #Genetics #MODY #PrecisionMedicine link.springer.com/article/10.1... 🔓

Really pleased to be working with @lcpilling.bsky.social and others investigating haemochromatosis, a surprisingly common rare disease with high penetrance in older adults! Recent publication highlights the effect of polygenic score on penetrance of HFE p.C282Y homozygotes. doi.org/10.1016/j.jh...

Systematic analysis of loss-of-function variants across MODY genes demonstrates gene-specific effects and expands the spectrum of INS variants causing MODY - Diabetologia Aims/hypothesis Accurate interpretation of loss-of-function (LOF) variants in MODY genes is essential for diagnosis but remains challenging, particularly for variants that are predicted to escape nons...

Systematic analysis of loss-of-function variants across MODY genes demonstrates gene-specific effects and expands the spectrum of INS variants causing MODY #MODY #Insulin #Genetics #DiabetesResearch link.springer.com/article/10.1... 🔓

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...

A list of highlights from the linked article

MODY Is Prevalent in Later-Onset Diabetes and Has Potential for Targeted Therapy but Is Challenging to Identify

Read more ➡️ doi.org/10.2337/db25-0545

MODY Is Prevalent in Later-Onset Diabetes and Has Potential for Targeted Therapy but Is Challenging to Identify Maturity onset diabetes of the young (MODY) can present after the age of 40 years, but its prevalence and clinical characteristics, and the utility of simp

A reminder that MODY (and type 1 diabetes) can present in older individuals and must remain in the differential diagnosis for new onset #diabetes across the lifespan diabetesjournals.org/diabetes/art...

MODY Is Prevalent in Later-Onset Diabetes and Has Potential for Targeted Therapy but Is Challenging to Identify Maturity onset diabetes of the young (MODY) can present after the age of 40 years, but its prevalence and clinical characteristics, and the utility of simp

Our new paper “MODY is prevalent in later-onset diabetes and has potential for targeted therapy but is challenging to identify” is out now in Diabetes !!! #diabetes #MODY

doi.org/10.2337/db25...

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”

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

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

Congratulations @luke-sharp.bsky.social for receiving the best abstract prize for early career researcher in EASD 2025 for his work on MODY in population.

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

Global perspectives on monogenic forms of diabetes - Diabetologia Monogenic forms of diabetes represent an uncommon but very heterogeneous subset of the disease, with variable associated clinical features and key differences in treatment options. In this review, we ...

Global perspectives on #MonogenicDiabetes: review explores recent advances, global diagnostic challenges and promising future directions—from genomic equity to innovative therapies. #GlobalHealth link.springer.com/article/10.1... 🔓

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

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...

Check out our new paper on “Medullary Thyroid Cancer Risk and Mortality in Carriers of Incidentally Identified MEN2A RET Variants” ja.ma/3I0VgsJ

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

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!