Eimear Kenny

Thank you for coming to the meeting and for your great talk!

We’re excited to share this work and hope it proves useful across GWAS, PRS, heritability, and environmental confounding studies.

Massive congratulations to @RoohyShemirani and our whole team for seeing this through.

Feedback and collaborations welcome! 🧵👇

9/9

Method is open-source & scalable 🚀
➡️ Python package: github.com/roohy/spc
➡️ Simulation framework: github.com/roohy/msprim...

8/9

Why does this matter?
As we move into diverse biobanks and rare variant discovery, we will need more methods. SPCs offer a modern toolkit for accurate, scalable correction of recent demographic structure.

7/9

Environmental confounding?
SPCs dramatically improved adjustment:
📉 Reduced Moran’s I more than PCs
📊 Avoided false heritability from geography
🧬 Preserved signal from true polygenic traits

6/9

Rare variant GWAS?
In UKBB inflation factor dropped from 7.6 (PCs) to 1.2 (SPCs) — helpful for uncovering real associations instead of noise.

5/9

In simulations, SPCs captured >90% of fine-scale population structure with fewer components than PCs, which explained <50%.

In GWAS of environmental phenotypes, SPCs reduced genomic inflation by 12%, while matching PC performance for highly heritable traits like height.

4/9

SPCs offer a novel solution:
✔️ Based on IBD graphs, not allele frequencies
✔️ Transforms local IBD sharing into continuous covariates using graph spectral theory
✔️ Works out-of-the-box with large datasets (tested on N ≈ 420K from UK Biobank)

3/9

Population structure is a major confounder in GWAS and heritability estimation.
Principal Components (PCs) have been the default — but they fall short for recent, non-linear, fine-scale structure, especially in rare variant analyses.

2/9

SPC: a SPectral Component approach to address recent population structure in genomic analysis Population structure is a well-known confounder in statistical genetics, particularly in genome-wide association studies (GWAS), where it can lead to inflated test statistics and spurious associations...

📢 Just posted: Our preprint introducing SPC — Spectral Components — is now live on medRxiv!

Led by Dr. Ruhollah Shemirani and years in the making, this method offers a robust, scalable way to adjust for recent population structure in genomic analyses.
🔗 www.medrxiv.org/content/10.1...

1/9

Oh no, I’m so sorry to hear this. Condolences to his family and friends.

A conclave of scientist ..

Very enjoyable visit to the Broad Clinical Lab in Burlington yesterday and a tour of their world class sequencing and omics facility 🧬. Really impressive.

And some really beautiful art work too…

Thanks @heidirehm.bsky.social and Niall Lennon for hosting.

#BlueSkyDrive #Broadies

A conclave of scientist ..

Very enjoyable visit to the Broad Clinical Lab in Burlington yesterday and a tour of their world class sequencing and omics facility 🧬. Really impressive.

And some really beautiful art work too…

Thanks @heidirehm.bsky.social and Niall Lennon for hosting.

#BlueSkyDrive #Broadies

Incredible GRC Genetics and Genomics conference line-up this year in Portland, Maine (www.grc.org/human-geneti...). With conference-maxxing sessions that run to 9:30pm!

Submission deadline is June 8th, conference July 6-11th.

Thanks Sarah! 💛

Thank Simone!!! 💛

Thanks Joe! 💛

Celebrating Women's History Month: Trailblazing Women in Human Genetics and Genomics ASHG President Sarah Tishkoff, PhD, celebrates women past and present who blaze trails in the human genetics and genomics field.

Honored to be featured in ASHG’s #WomensHistoryMonth celebration! Huge thanks to @GeneticsSociety & @sarahtishkoff.bsky.social for the recognition.

Grateful to stand alongside incredible women shaping human genetics & genomics! 💙 #ASHG #WomenInSTEM

www.ashg.org/publications...

🌍 Hillerød, Denmark from May 19-23, 2025,

🚨 Abstract submission closes March 15, 2025—still a few spots left! Submit yours here: sciencecluster.dk/event/genomic-mechanisms-of-disease-2025

📢 Excited to be an invited speaker at the @NovoNordiskFoundation Science Cluster Conference, "Genomic Mechanisms of Disease"!

Join me to explore cutting-edge research in med & pop gen, ML models of biology, and translational therapeutics.🔬✨

#Genomics #AIinMedicine #GeneticResearch #Conference

📹🍿🧬 Check out @yunfeng-ruan.bsky.social's recent talk at the @broadinstitute.org, "Polygenic risk scores: method development and application" in our growing collection of videos on the @prsdiversity.bsky.social website primedconsortium.org/education#vi...

Seattle’s newest unicorn: Truveta lands $320M to fuel creation of massive new genome project The Truveta team at its Bellevue, Wash., headquarters last year. (Truveta Photo) Seattle-area health data company Truveta announced $320 million in

Truveta has built a database of 120M de-identified EHRs for digital phenotyping—and now they're teaming up with Regeneron and Illumina to sequence 10M patients across 30 US health systems.

🧬 Major move for precision medicine!

www.geekwire.com/2025/seattle...

One month left until the CSHL Biology of Genomes abstract deadline! 👇👇👇

Where else can you dive into all things genomics? 🧬✨

Interactive Workshops Questions: digitalprograms@ashg.org Got a great idea for an interactive workshop? Share your expertise and inspire others at the ASHG Annual Meeting. Whether you’re teaching new techniques, discussing...

🔗 www.ashg.org/meetings/202...

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Featured Symposia Questions: programs@ashg.org Looking to make your mark on the ASHG Annual Meeting? Propose a Featured Symposium on a topic that excites you. Our Program Committee is here to provide guidance and suppo...

🚨 Calling human geneticists! 🚨

Featured Symposium & Interactive Workshop submissions for #ASHG2025 are OPEN! 🧬✨

Got cutting-edge research or ideas to share? Now’s the time to showcase them on a global stage. Spread the word & submit! 🌍📝

🔗 www.ashg.org/meetings/202...

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#HumanGenomics #ASHG25

Thrilled to be a part of the Leena Peltonen School of Human Genomics this year -- an opportunity for PhD students to learn and interact 1:1 with many experts (and genuinely nice people) in the field!

Apply by March 7th at: lpshg.org
Program runs July 27-31 at the Wellcome Genome Campus, UK.

Evolving knowledge of “red flag” clinical features associated with TTR p.(Val142Ile) in a diverse electronic health record-linked biobank Previous studies have established “red flags” that raise clinical suspicion for the hereditary form of transthyretin amyloidosis (ATTRv). However, the…

Read the full study here: 🔗 www.sciencedirect.com/science/arti...

#Genomics #Amyloidosis #ATTRv #PrecisionMedicine #EHR

3/

Key findings:

➡️ Variant carriers show early signs of cardiomyopathy, neuropathy, & proteinuria.
➡️ Recognizing these age-dependent red flags can enable earlier diagnosis & treatment.

2/