Josh Weinstock
@joshweinstock.bsky.social
Assistant Professor in the Department of Human Genetics at Emory University. Statistical genetics and genomics + genetic epidemiology of somatic mosaicism.
weinstocklab.org
weinstocklab.org
The IGH and IGL mutations in particular had really large effect sizes, so we then did a GWAS of a combined IGH + IGL phenotype, which resulted in a single hit: GRAMD1B. Remarkably, this is well characterized risk locus for CLL, suggesting that we are converging on CLL relevant biology.
October 14, 2025 at 9:27 PM
The IGH and IGL mutations in particular had really large effect sizes, so we then did a GWAS of a combined IGH + IGL phenotype, which resulted in a single hit: GRAMD1B. Remarkably, this is well characterized risk locus for CLL, suggesting that we are converging on CLL relevant biology.
We then quantified the variance explained on a liability scale of CH to 30 common aging-related diseases. CH explains far more 'liability' scale variance for hematologic malignancies than other classes (as one would expect), though chronic kidney disease appears high here as well.
October 14, 2025 at 9:27 PM
We then quantified the variance explained on a liability scale of CH to 30 common aging-related diseases. CH explains far more 'liability' scale variance for hematologic malignancies than other classes (as one would expect), though chronic kidney disease appears high here as well.
New hits are generally indeed "weaker" than most classic CH drivers, suggesting that these are just underneath the "tip of the iceberg". We also replicate the telomere attrition mechanism reported here www.nature.com/articles/s41..., finding that the phenomenon is broader than previously observed
October 14, 2025 at 9:27 PM
New hits are generally indeed "weaker" than most classic CH drivers, suggesting that these are just underneath the "tip of the iceberg". We also replicate the telomere attrition mechanism reported here www.nature.com/articles/s41..., finding that the phenomenon is broader than previously observed
The strongest hits are indeed strongly enriched for canonical CH genes, but we also find non-coding mutations at FGF1, UGT2B7, DGKB, the TERT promoter, chr17 centromere, and immunoglobulin loci:
October 14, 2025 at 9:27 PM
The strongest hits are indeed strongly enriched for canonical CH genes, but we also find non-coding mutations at FGF1, UGT2B7, DGKB, the TERT promoter, chr17 centromere, and immunoglobulin loci: