| Title: | Body mass index stratification optimizes polygenic prediction of type 2 diabetes in cross-biobank analyses |
| Journal: | Nature Genetics |
| Published: | 11 Jun 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/38862855/ |
| DOI: | https://doi.org/10.1038/s41588-024-01782-y |
Publication 11879
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Abstract
Type 2 diabetes (T2D) shows heterogeneous body mass index (BMI) sensitivity. Here, we performed stratification based on BMI to optimize predictions for BMI-related diseases. We obtained BMI-stratified datasets using data from more than 195,000 individuals (nT2D = 55,284) from BioBank Japan (BBJ) and UK Biobank. T2D heritability in the low-BMI group was greater than that in the high-BMI group. Polygenic predictions of T2D toward low-BMI targets had pseudo-R2 values that were more than 22% higher than BMI-unstratified targets. Polygenic risk scores (PRSs) from low-BMI discovery outperformed PRSs from high BMI, while PRSs from BMI-unstratified discovery performed best. Pathway-specific PRSs demonstrated the biological contributions of pathogenic pathways. Low-BMI T2D cases showed higher rates of neuropathy and retinopathy. Combining BMI stratification and a method integrating cross-population effects, T2D predictions showed greater than 37% improvements over unstratified-matched-population prediction. We replicated findings in the Tohoku Medical Megabank (n = 26,000) and the second BBJ cohort (n = 33,096). Our findings suggest that target stratification based on existing traits can improve the polygenic prediction of heterogeneous diseases.</p>
12 Authors
- Takafumi Ojima
- Shinichi Namba
- Ken Suzuki
- Kenichi Yamamoto
- Kyuto Sonehara
- Akira Narita
- Yoichiro Kamatani
- Gen Tamiya
- Masayuki Yamamoto
- Toshimasa Yamauchi
- Takashi Kadowaki
- Yukinori Okada
1 Application
| Application ID | Title |
|---|---|
| 47821 | Trans-ethnic GWAS meta-analysis and exploration of trait-relevant genetic architecture. |
Enabling scientific discoveries that improve human health