T2D Risk × Insulin Sensitivity Browser

What it shows

An interactive browser exploring how T2D risk variants from the largest type 2 diabetes GWAS to date (Suzuki et al., Nature, 2024; >2.5 million individuals) associate with 23 insulin sensitivity indices (ISIs) derived from fasting blood measurements and OGTTs. It shows, for each variant, which ISIs it associates with, the direction of effect, whether the effect acts through fasting insulin resistance or post-load glucose handling, and how much of the effect is mediated through BMI. All results are shown for both BMI-adjusted and BMI-unadjusted models.

How to use it

1. Open the Heatmap tab for an effect-size overview across all variants x 23 ISIs, with a searchable data table.
2. Use BMI Comparison to view BMI-adjusted vs unadjusted heatmaps side by side, including a per-variant Δβ calculator.
3. Check Volcano plots (β vs −log₁₀ p) for a single index or all 23 at once.
4. Select a variant in Effect Profile to see a lollipop chart of its effect across all 23 ISIs.
5. Use BMI Mediation for a Baron-Kenny proportion-mediated bar chart, or Data Browser / Gene Summary to search, filter and download the underlying results.

All tabs respond to a shared filter panel (gene name, rsID, index group, p-value threshold, minimum |β|).

Data behind the app

ISIs cover three timepoint groups: fasting (inv-FIns, inv-HOMA-IR, QUICKI, Raynaud SI, Belfiore basal, ISI basal, Bennett SI, Avignon SI0, FIRI, inv-FIns/FGlu), OGTT 0-120 min (inv-Ins120, inv-Glu120, ISI 120, inv-Ins/Glu120, Gutt Index, Avignon SI120, Avignon SIM), and OGTT 0-30-120 min (Stumvoll Modi, Stumvoll Dem, inv-IFC, BIGTT SI, Matsuda, Matsuda AUC). BMI mediation uses the Baron-Kenny formula PM = (β_total − β_direct) / |β_total| × 100, restricted to variants with |β_total| ≥ 0.005 across ≥ 3 ISIs, with individual PMs clamped to ±300% before taking the median.

Related publication

This browser accompanies Suleman S, Ängquist L, Linneberg A, Hansen T, Grarup N. “Exploring the genetic intersection between obesity-associated genetic variants and insulin sensitivity indices.” Scientific Reports 15, 15761 (2025). https://doi.org/10.1038/s41598-025-98507-w, building on T2D variants from Suzuki et al., Nature 627, 347-357 (2024). It is not the JCEM 2024 paper on fasting and OGTT-based insulin sensitivity indices.

Live app: https://sufyansuleman.github.io/isi_t2d_nat_24/