A new study from the eMERGE consortium reports on a pipeline for the generation and reporting of polygenic risk scores for ten diseases to diverse populations in a clinical setting Niall J Lennon Eimear Kenny AllofUsResearch Broad Institute

nature.com/articles/s4159…

Important work from eMERGE which brings polygenic scores to the cusp of prime time.

Selection, optimization and validation of ten chronic disease polygenic risk scores for clinical implementation in diverse US populations nature.com/articles/s4159…

Nice study showing polygenic risk alters the penetrance of monogenic kidney disease. This will be the norm in every disease, but nice to see the satisfying results.

Note the striking difference between high (OR=54.4) vs low (OR=3.03) PRS groups among rare variant carriers.…

Congratulations Atlas Khan on the publication!

Excited to share our newly published paper rdcu.be/dtI4s on the interplay of monogenic and polygenic risk in CKD. Joint analysis of UK Biobank and AllofUsResearch by Atlas Khan shows that polygenic risk alters the penetrance of kidney disease in ADPKD and COL4A-AN!

Important work! Scaling is such an important step on PRS/PGS which often isn't given the attention it deserves.

PGS adjustments include the regression based method using PCA loadings originally proposed by Amit V. Khera et al (2019) to centre means (Z_norm1) & the update from Atlas Khan / @eMERGENetwork_ et al. (2022) to equalise the variances (Z_norm2). Here's an example using 1000G:

A new preprint by Gupta et al. reports a missense variant that cancels out the pathogenic effects of APOL1 risk variants for kidney disease in African Americans. This is one of the most impressive disease modifier variants I’ve seen so far. Let’s dive deep…

In our groups first invited commentary we provide clinical context and future directions for two #HidradenitisSuppurativa genetic studies that were published this month.

🧵

jamanetwork.com/journals/jamad…

We would say it takes a village, but it is more fitting to say it takes a consortium to produce our most recently published work in Nature today. Thank you to each Kidney Precision Medicine Project and Human BioMolecular Atlas Program (HuBMAP) contributor across the consortium who made this atlas possible.

nature.com/articles/s4158…

📢 ICYMI Nature Genetics
📰 Genome-wide association analyses define pathogenic signaling pathways and prioritize drug targets for IgA nephropathy
🧑🏾‍🤝‍🧑🏼 Krzysztof Kiryluk Ali G. Gharavi Columbia Nephrology and team
⬇️
go.nature.com/42Qf86w

Our new GWAS for IgA nephropathy is out today Nature Genetics; a global collaboration between Columbia Nephrology and 50+ kidney centers on the 'not so common' kidney disease; >10K cases included; 30 risk loci, new polygenic score, new drug targets, and more...
nature.com/articles/s4158…

Polygenic risk affects the penetrance of monogenic kidney disease medrxiv.org/cgi/content/sh… #medRxiv

New medRxiv from our group - polygenic risk affects the penetrance of monogenic kidney disease: medrxiv.org/cgi/content/sh… - massive combined analysis of the UK Biobank & AllofUsResearch by Atlas Khan Columbia Nephrology Columbia DBMI @eMERGENetwork_

Our paper on 'Mapping genomic regulation of kidney disease and traits through high-resolution and interpretable eQTLs' is published!

Congrats Michelle McNulty Seong Kyu Han Christopher Benway Anya Dongwon Lee Matt Sampson Ben Humphreys Parker Wilson go.nature.com/3NiCygX

Genomic disorders (GDs) are linked to many comorbid outcomes, including CKD. This study detected undiagnosed GDs in both children and adults with CKD. Identification of GDs can enable a precise genetic diagnosis, inform prognosis, and help stratify risk bit.ly/j2022060725wk

APOL1 genotype effects on kidney disease development vary among specific causes of kidney disease. This study suggests rare missense gene variants in the inflammasome pathway may explain some of the clinical heterogeneity in APOL1-associated CKD bit.ly/JASN094

Researchers Krzysztof Kiryluk Lili Liu perform a genome-wide association study for serum IgA levels, an antibody blood protein involved in infectious disease resistance and inflammatory disorders

go.nature.com/3Xf6Hjp

Our genetic study of serum IgA levels in 41K individuals is now out Nature Communications. Big thanks to our collaborators from @eMERGENetwork_, MESA study, Columbia Nephrology, Columbia DBMI and many others...
nature.com/articles/s4146…

Genomic Disorders (GDs) are linked to comorbid outcomes. This study suggests identification of GDs in patients with CKD can enable a precise genetic diagnosis, inform prognosis, & help stratify risk bit.ly/j2022060725

Columbia Nephrology Columbia Medicine Harold Feldman Krzysztof Kiryluk