Excited to share our latest foray into studying the ways in which germline variation gives rise to somatic variation in aging blood: www.medrxiv.org/content/10.6... In work led by @prarthana-s-r.bsky.social , we map how common and rare germline variation links to (somatic) passenger mutations 🧬🧵👇

Multi-ancestry analysis of 791K whole genomes reveals the genetic, geographic, and phenotypic correlates of somatic passenger mutations in blood

Clonal hematopoiesis (CH), an aging-related expansion of hematopoietic stem cell (HSC) clones, is associated with hematologic malignancy, cardiovascular disease, and mortality. Most clonal expansions,...

medrxiv.org

Anyone have a good workflow for downloading GWAS summary statistics from All of Us? Totally in compliance with their policy, but the file is simply too large (1.7GB), and downloads time out. We split into several 10mb files, but that is painful to download.

Here's our R package for interacting with WGS derived GWAS summary statistics with many rare variants (from e.g. UKB or AofUs). It uses duckdb underneath so it's fast. Includes some helpful tie ins to Open Targets / Encode Screen / Ensembl APIs for annotation. weinstocklab.github.io/gwasplot/ind...

STATGEN 2026 will be in Atlanta @emoryrollins.bsky.social - see more info here: statgen26.emory.edu

How do GWAS and rare variant burden tests rank gene signals? In new work @nature.com with @hakha.bsky.social, @jkpritch.bsky.social, and our wonderful coauthors we find that the key factors are what we call Specificity, Length, and Luck! 🧬🧪🧵 www.nature.com/articles/s41...

Specificity, length and luck drive gene rankings in association studies - Nature

Genetic association tests prioritize candidate genes based on different criteria.

nature.com

What happens if you search the genomes of ~490K adults for variants that associate with age at blood draw? We actually did this crazy idea, using the UKB WGS (from peripheral blood). Turns out this 'discovers' classic clonal hematopoiesis drivers and more 🧵👇 www.medrxiv.org/content/10.1... #ASHG

Genome-wide characterization of clonal hematopoiesis reveals extensive non-coding putative driver mutations

As humans age, we acquire somatic mutations in our blood, leading to clonal hematopoiesis (CH). Despite the prevalence of clonal hematopoiesis (CH) in aged individuals, recent searches for selective s...

medrxiv.org

Exciting updates!! (1) I just opened my lab at Boston Children’s Hospital (Harvard-affiliated) (2) I’m hiring a postdoc focused on integrating GWAS and functional genomic data. Reach out if you’re interested or connect at ASHG next week! (3) Learn more at stroberlab.com

Strober Lab

The Strober lab is a computational group at Boston Children's Hospital (a Harvard Medical School affiliated hospital) focused on developing statistical and machine learning tools applied to human gene...

stroberlab.com

Excited for a major milestone in our efforts to map enhancers and interpret variants in the human genome: The E2G Portal! e2g.stanford.edu This collates our predictions of enhancer-gene regulatory interactions across >1,600 cell types and tissues. Uses cases 👇 1/

I wrote about gene-gene interactions (epistasis) and the implications for heritability, trait definitions, natural selection, and therapeutic interventions. Biology is clearly full of causal interactions, so why don't we see them in the data? A 🧵:

Beneath the surface of the sum

When genetic interactions matter and when they don't

open.substack.com

Really excited to share our new PRS method, developed with @aprilkim.bsky.social and @alexisbattle.bsky.social ! Our approach is to use a lot of recently developed functional annotations to better estimate the weights of the SNPs. www.medrxiv.org/content/10.1...

Polygenic prediction of phenotypes with a neural empirical Bayes approach

Polygenic risk scores (PRS) estimate the expected value of a phenotype based on individual genotypes. Although statistical approaches for calculating PRS have advanced considerably in recent years, fe...

medrxiv.org

Happy to share our work characterizing functional rare SVs in rare diseases with long-read genome sequencing and transcriptomic outlier data: genome.cshlp.org/content/earl...

Sharing some of our lecture slides on statistical genetics! 🧬 Co-taught with Mike Epstein, Dave Cutler, Karen Conneely, Jingjing Yang, Jian Hu. Mendelian randomization: weinstocklab.org/lecture_slid... Biobank scale GWAS methods: weinstocklab.org/lecture_slid... Hope they're helpful!

We have multiple postdoc positions available in my group at NYU. Join us if you're interested in complex trait genetics and biology. More information about the lab on our website: mostafavilab.org

Specificity, length, and luck: How genes are prioritized by rare and common variant association studies https://www.biorxiv.org/content/10.1101/2024.12.12.628073v1

Excited to see our study on genetic regulation in heterogeneous differentiating cultures out in final form! www.cell.com/cell-genomics/fulltext/S2666-979X(24)00330-6

Cell type and dynamic state govern genetic regulation of gene expression in heterogeneous differentiating cultures

Popp et al. generate dozens of cell types from 53 human iPSC lines in order to characterize the dynamic genetic regulation of gene expression across early stages of cellular differentiation. Accessing...

cell.com

I'm developing a pipeline to call CHIP mutations in UK Biobank using the DNA Nexus RAP that is fast/cheap/reproducible. Initial results are promising; calls looks reasonable and cost to do this across all of UKB is likely < 500$. Feel free to DM if of interest.

Great talk from Zeyun Lu on integrating cis-eQTLs with perturb-seq to increase discovery in Mendelian randomization #ASHG2023 !