Mike Weedon
@mnweedon.bsky.social
Reposted by Mike Weedon
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
We’ll be providing our filtered AoU WGS plink pgens for all registered users: watch this space
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”
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”
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...
www.biorxiv.org
November 10, 2025 at 1:10 PM
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
We’ll be providing our filtered AoU WGS plink pgens for all registered users: watch this space
Reposted by Mike Weedon
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”
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”
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...
www.biorxiv.org
November 8, 2025 at 9:31 AM
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”
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”
Reposted by Mike Weedon
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
November 8, 2025 at 9:31 AM
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
Reposted by Mike Weedon
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
#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
doi.org
November 3, 2025 at 11:02 AM
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
#MODY #monogenicdiabetes
Population prevalence, penetrance, and mortality for genetically confirmed MODY: academic.oup.com/jcem/article...
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
academic.oup.com
November 3, 2025 at 8:32 AM
Population prevalence, penetrance, and mortality for genetically confirmed MODY: academic.oup.com/jcem/article...
Reposted by Mike Weedon
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
October 29, 2025 at 11:17 AM
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
Reposted by Mike Weedon
🎉 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...
"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...
October 16, 2025 at 9:16 PM
🎉 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...
"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...
Reposted by Mike Weedon
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) 🧪
@exeter.ac.uk
Polygenic risk for T2D modifies the onset and phenotypic variability of maturity-onset diabetes of the young (MODY) 🧪
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.
bit.ly
October 14, 2025 at 6:41 PM
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) 🧪
@exeter.ac.uk
Polygenic risk for T2D modifies the onset and phenotypic variability of maturity-onset diabetes of the young (MODY) 🧪
Reposted by Mike Weedon
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.
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...
www.medrxiv.org
September 15, 2025 at 8:28 AM
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.
Reposted by Mike Weedon
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...
www.nature.com/articles/s42...
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...
www.nature.com
September 9, 2025 at 1:25 PM
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...
www.nature.com/articles/s42...
Reposted by Mike Weedon
Our paper is now out on Diabetes!
diabetesjournals.org/diabetes/art...
diabetesjournals.org/diabetes/art...
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
diabetesjournals.org
August 27, 2025 at 1:42 PM
Our paper is now out on Diabetes!
diabetesjournals.org/diabetes/art...
diabetesjournals.org/diabetes/art...
Reposted by Mike Weedon
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
Polygenic Background Contributes to GCK-MODY Clinical Presentation and Glycaemic Variability https://www.medrxiv.org/content/10.1101/2025.08.04.25332935v1
August 11, 2025 at 4:57 PM
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
Reposted by Mike Weedon
🚨 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!
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!
August 6, 2025 at 6:27 PM
🚨 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!
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!
Reposted by Mike Weedon
🚨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
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
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...
bmcmedicine.biomedcentral.com
July 23, 2025 at 1:50 PM
🚨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
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
Reposted by Mike Weedon
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
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
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...
thelancet.com
July 22, 2025 at 6:01 AM
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
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
Reposted by Mike Weedon
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...
🔗 doi.org/10.1016/j.mo...
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…
www.sciencedirect.com
July 3, 2025 at 2:23 PM
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...
🔗 doi.org/10.1016/j.mo...
Reposted by Mike Weedon
Population prevalence, penetrance, and mortality for genetically confirmed MODY https://www.medrxiv.org/content/10.1101/2025.06.30.25330354v1
July 1, 2025 at 1:57 AM
Population prevalence, penetrance, and mortality for genetically confirmed MODY https://www.medrxiv.org/content/10.1101/2025.06.30.25330354v1
Reposted by Mike Weedon
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
🗓 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
June 27, 2025 at 10:00 AM
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
🗓 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
Reposted by Mike Weedon
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
#MonogenicDiabetes
MODY is prevalent in later-onset diabetes, has potential for targeted therapy but is challenging to identify https://www.medrxiv.org/content/10.1101/2025.06.17.25329143v1
June 19, 2025 at 12:05 PM
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
#MonogenicDiabetes
Reposted by Mike Weedon
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
Read for free here - rdcu.be/eprel
June 4, 2025 at 11:22 PM
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
Read for free here - rdcu.be/eprel
Reposted by Mike Weedon
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!
NEUROD1 and PDX1 are low penetrance causes of MODY while rare variants in APPL1 and WFS1 are not associated with MODY https://www.medrxiv.org/content/10.1101/2025.05.07.25327066v1
June 4, 2025 at 12:36 PM
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!
Reposted by Mike Weedon
Congratulations @carolinefwright.bsky.social for being elected to a fellow of the Academy of Medical Sciences! 🍾!
news.exeter.ac.uk/faculty-of-h...
@nihrexeterbrc.bsky.social
news.exeter.ac.uk/faculty-of-h...
@nihrexeterbrc.bsky.social
May 22, 2025 at 7:20 PM
Congratulations @carolinefwright.bsky.social for being elected to a fellow of the Academy of Medical Sciences! 🍾!
news.exeter.ac.uk/faculty-of-h...
@nihrexeterbrc.bsky.social
news.exeter.ac.uk/faculty-of-h...
@nihrexeterbrc.bsky.social
Reposted by Mike Weedon
⬇️ again. I feel the need to re-post this point pretty much every week! Benign variants are not low penetrance.
Key points:
1. Observation in a single case != pathogenic
2. Pre-selected cohorts warrant special care (controls are important!)
3. To make claims about reduced penetrance (as they do in the discussion) we first need evidence of pathogenicity (which there isn’t here)
6/7
1. Observation in a single case != pathogenic
2. Pre-selected cohorts warrant special care (controls are important!)
3. To make claims about reduced penetrance (as they do in the discussion) we first need evidence of pathogenicity (which there isn’t here)
6/7
May 1, 2025 at 8:37 AM
⬇️ again. I feel the need to re-post this point pretty much every week! Benign variants are not low penetrance.
Reposted by Mike Weedon
Our new paper updating GRS2 with a new tool to easily generate standardised T1DGRS 🧬 Thanks to Seth Sharp, @annagloyn.bsky.social, Richard Oram and @mnweedon.bsky.social for a great collaboration! tinyurl.com/4bsaz9hx
Standardized Measurement of Type 1 Diabetes Polygenic Risk Across Multiancestry Population Cohorts
Amber M. Luckett, Richard A. Oram, Aaron J. Deutsch, Hector I. Ortega, Diane P. Fraser, Kaavya Ashok, Alisa K. Manning, Josep M. Mercader, Manuel A. Rivas,
tinyurl.com
April 25, 2025 at 10:44 AM
Our new paper updating GRS2 with a new tool to easily generate standardised T1DGRS 🧬 Thanks to Seth Sharp, @annagloyn.bsky.social, Richard Oram and @mnweedon.bsky.social for a great collaboration! tinyurl.com/4bsaz9hx