# SNPgen: Phenotype-Supervised Genotype Representation and Synthetic Data Generation via Latent Diffusion

arXiv: https://arxiv.org/abs/2603.10873 · HTML: https://mlsanity.com/paper/2603.10873/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Placed in Flow matching, time series and science, one of 14 directions in Diffusion models.
- Builds on 10 of its 31 references that are in the map.
- First posted on arXiv 11 Mar 2026.

## Placed in

- Diffusion models / [Flow matching, time series and science](https://mlsanity.com/diffusion/flow-matching-time-series-and-science/)

## Builds on (most cited first, 10 of 10)

- [Attention Is All You Need](https://mlsanity.com/paper/1706.03762/) (2017)
- [Denoising Diffusion Probabilistic Models](https://mlsanity.com/paper/2006.11239/) (2020)
- [U-Net: Convolutional Networks for Biomedical Image Segmentation](https://mlsanity.com/paper/1505.04597/) (2015)
- [High-Resolution Image Synthesis with Latent Diffusion Models](https://mlsanity.com/paper/2112.10752/) (2021)
- [XGBoost: A Scalable Tree Boosting System](https://mlsanity.com/paper/1603.02754/) (2016)
- [Elucidating the Design Space of Diffusion-Based Generative Models](https://mlsanity.com/paper/2206.00364/) (2022)
- [Spectral Normalization for Generative Adversarial Networks](https://mlsanity.com/paper/1802.05957/) (2018)
- [Real-valued (Medical) Time Series Generation with Recurrent Conditional GANs](https://mlsanity.com/paper/1706.02633/) (2017)
- [Routes for breaching and protecting genetic privacy](https://mlsanity.com/paper/1310.3197/) (2013)
- [Generating Synthetic Genotypes using Diffusion Models](https://mlsanity.com/paper/2412.03278/) (2024)

## Abstract (arXiv)

Polygenic risk scores and other genomic analyses require large individual-level genotype datasets, yet strict data access restrictions impede sharing. Synthetic genotype generation offers a privacy-preserving alternative, but most existing methods operate unconditionally, producing samples without phenotype alignment, or rely on unsupervised compression, creating a gap between statistical fidelity and downstream task utility. We present SNPgen, a two-stage conditional latent diffusion framework for generating phenotype-supervised synthetic genotypes. SNPgen combines GWAS-guided variant selection (1,024-2,048 trait-associated SNPs) with a variational autoencoder for genotype compression and a latent diffusion model conditioned on binary disease labels via classifier-free guidance. Evaluated on 458,724 UK Biobank individuals across four complex diseases (coronary artery disease, breast cancer, type 1 and type 2 diabetes), models trained on synthetic data matched real-data predictive performance in a train-on-synthetic, test-on-real protocol, approaching genome-wide PRS methods that use 2-6× more variants. Privacy analysis confirmed zero identical matches, near-random membership inference (AUC ≈ 0.50), preserved linkage disequilibrium structure, and high allele frequency correlation (r ≥ 0.95) with source data. A controlled simulation with known causal effects verified faithful recovery of the imposed genetic association structure.