Isy Foote

Thank you @andrewgrotzinger.bsky.social it has been the most amazing few years as a P-BADGER lab member ❤️🧬

Estimation and mapping of the missing heritability of human phenotypes - Nature WGS data were used from 347,630 individuals with European ancestry in the UK Biobank to obtain high-precision estimates of coding and non-coding rare variant heritability for 34 co...

First time on Bsky and first big announcement!

I am excited to announce that our new study explaining the missing heritability of many phenotypes using WGS data from ~347,000 UK Biobank participants has just been published in @Nature.

Our manuscript is here: 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.

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...

The role of untranslated region variants in Mendelian disease: a review - European Journal of Human Genetics European Journal of Human Genetics - The role of untranslated region variants in Mendelian disease: a review

Not all pathogenic variants are in coding regions! 👀
📢 This review highlights Mendelian disease-causing UTR variants, their mechanisms, and implications for clinical interpretation. 🧬 #Mendelian #UTRvariants #ejhg

www.nature.com/articles/s41...

Key questions for the future of amyloid research in dementia: a framework for integrating complex datasets - Molecular Psychiatry Molecular Psychiatry - Key questions for the future of amyloid research in dementia: a framework for integrating complex datasets

A key (too often ignored) aspect of Alzheimer's research is translation of findings between familial disease, specialist clinics, and general population. In this piece we identify key unanswered research questions and describe a framework for knowledge integration.

www.nature.com/articles/s41...

I'm looking for a PhD student to do some trailblazing at the frontier of personality genomics and lifespan gene-environment transactions (start Fall 2026)! If you want to work with me: psychology.msu.edu/graduatestud...
(PS @drmeltemyucel.bsky.social is taking a student too, in moral psych/dev!)

Super cool study looking at understanding age-dependent impacts on genetic variance!!

Some recent data:

- First scores for frailty measurements (@isyfoote.bsky.social & @andrewgrotzinger.bsky.social‬): www.pgscatalog.org/publication/...
- Comprehensive comparison of type 2 diabetes PGS in Qatari Biobank: www.pgscatalog.org/publication/...

Share PGS 👉 www.PGSCatalog.org/submit!

Uncovering the multivariate genetic architecture of frailty with genomic structural equation modeling - Nature Genetics Multivariate genome-wide association analyses of the latent genetic architecture of frailty identify one general factor of genetic overlap across all frailty deficits and six factors indexing a shared...

New work in Nature Genetics from IBG members lead by @isyfoote.bsky.social (along with @andrewgrotzinger.bsky.social) examining different measures of frailty using Genomic SEM. Findings reveal six genomic factors with unique biological pathways and clinical correlates. www.nature.com/articles/s41...

What evidence do we have on the Social Determinants of Dementia (SDOD)?

Delighted that this scoping review, a year or so in the making, is now published in @alzdemjournals.bsky.social. Expertly led by Anouk Geraets, we identified...

doi.org/10.1002/alz....

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Structural variation in 1,019 diverse humans based on long-read sequencing - Nature Intermediate-coverage long-read sequencing in 1,019 diverse humans from the 1000 Genomes Project, representing 26 populations, enables the generation of comprehensive population-scale structural variant catalogues comprising common and rare alleles.

Nature research paper: Structural variation in 1,019 diverse humans based on long-read sequencing

go.nature.com/3GI9EWC

This is figure 1, which shows study design and analysis pipeline.

Differences in physical, social, and sociopolitical factors across the world have resulted in marked disparities in healthy ageing across countries, according to an analysis in Nature Medicine. go.nature.com/3UfJ8GU #medsky 🧪

Design and model choices shape inference of age-varying genetic effects on complex traits Understanding how genetic influences on complex traits change with age is a fundamental question in genetic epidemiology. Both cross-sectional (between-subject) and longitudinal (within-subject) appro...

🚨New preprint is out!

How do genetic effects on complex traits change with age? In this work, we compare different approaches to obtain age-varying genetic effects, and show how design and modeling choices can impact the conclusions we draw.
shorturl.at/17snd
A thread 🧵👇

Translating lifestyle interventions for optimal brain health in Africa Nature Reviews Neurology, Published online: 11 July 2025; doi:10.1038/s41582-025-01104-8This Perspective article explores the efficacy of multimodal lifestyle interventions to tackle the rising incidence of dementia in low- and middle-income countries. The authors discuss a contextual adaptation of the Finnish FINGER trial, Africa-FINGERS, which is pioneering a culturally relevant, multidomain approach to dementia risk reduction for African settings.

ICYMI: New online! Translating lifestyle interventions for optimal brain health in Africa

This is figure 2, which shows organ age estimates predict future age-related disease.

In a large-scale proteomic study of biological aging of 11 organs, the biological ages of the brain and immune system emerged as strong predictors of healthspan and longevity, according to a paper in Nature Medicine. go.nature.com/44nLb1M #medsky 🧪

Bell et al. report that multisite chronic pain, unlike single-site, in older adults is linked to faster cognitive decline and increased AD pathology, particularly in APOE-ɛ4 carriers. This supports multisite pain as a risk factor for AD dementia. Read at buff.ly/tXL0Qro
@TylerBellPhD

Exome sequencing and analysis of 44,028 British South Asians enriched for high autozygosity Genes and Health (G&H) is a biomedical study of adult British-Pakistani and -Bangladeshi research volunteers enriched for autozygosity. We performed whole exome sequencing in 44,028 G&H participants, ...

Preprint alert! 🚨
doi.org/10.1101/2025...

Our manuscript on Exome sequencing and analysis of 44,028 British South Asians, using @genesandhealth.bsky.social is now available at @medrxivpreprint.bsky.social!

We present several great results, and I’m thrilled to highlight the pieces I worked on:

📣📣 Preprint just out from the awesome Xilin Jiang, Yujie Zhao & co!

Pleiotropic heritability quantifies the shared genetic variance of common diseases www.medrxiv.org/content/10.1...

The overlap of disease aetiologies is surprisingly pervasive... ~50% of common disease heritability is pleiotropic!

External link live! Please share widely :-)

WE ARE RECRUITING! 🥳

Are you an epidemiologist with strong quantitative skills and an interest in contributing to exciting research into the genetic architecture of vascular dementia? Come join our friendly and productive team at UCL!

shorturl.at/aZ5Ua