Disease Heterogeneity | Tanigawa Lab

Single-cell multiregion epigenomic rewiring in Alzheimer’s disease progression and cognitive resilience

Thu, 04 Sep 2025 00:00:00 +0000

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline, yet its epigenetic underpinnings remain elusive.

Disease heterogeneity dissection

Tue, 01 Jul 2025 00:00:00 +0000

Diagnosis for the same disease affects individuals differently. However, we don’t know how best to represent biologically meaningful axes of variation within a disease, beyond the standard case vs. control comparison or proxy measure of severity. We combine human genetics, causal inference, and modern AI to address this challenge.

Decomposition of genetic associations across many phenotypes
Causal representation learning from pleiotropic associations
Assessing the biological bases of disease subtypes

Representative studies

UK Biobank Latent Components Obesity +1 more

Components of genetic associations across 2,138 phenotypes in the UK Biobank highlight adipocyte biology

We developed DeGAs to decompose shared genetic associations across 2,138 UK Biobank phenotypes and identify their underlying pleiotropic structure.

Yosuke Tanigawa, Ph.D.

• Dec 31, 2019 • 1 min read

Polygenic Scores Latent Components Disease Heterogeneity

Polygenic risk modeling with latent trait-related genetic components

Polygenic risk score (PRS) has been proposed for disease risk prediction with potential clinical relevance for some traits, but its personalized interpretation is generally …

Feb 8, 2021 • 1 min read

UK Biobank Phenotyping Latent Components +1 more

A cross-population atlas of genetic associations for 220 human phenotypes

Using a set of GWAS summary statistics of diseases characterized from both European (UK Biobank and FinnGen) and East Asian (Biobank Japan) populations, we dissected latent DeGAs …

Sep 30, 2021 • 1 min read

Human microglial state dynamics in Alzheimer's disease progression

Thu, 28 Sep 2023 00:00:00 +0000

Here we report 194,000 single-nucleus microglial transcriptomes and epigenomes across 443 human subjects and diverse Alzheimer’s disease pathological phenotypes.

Polygenic risk modeling with latent trait-related genetic components

Mon, 08 Feb 2021 00:00:00 +0000

Polygenic risk score (PRS) has been proposed for disease risk prediction with potential clinical relevance for some traits, but its personalized interpretation is generally difficult, especially when there exist disease subtypes driven by different genetic components.