| Title: | A PheWAS approach to identify associations of GBA1 variants with comprehensive phenotypes beyond neurological diseases |
| Journal: | npj Parkinson's Disease |
| Published: | 17 Mar 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40097465/ |
| DOI: | https://doi.org/10.1038/s41531-025-00901-8 |
| URL: | https://www.nature.com/articles/s41531-025-00901-8.pdf |
Publication 15939
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Abstract
Given the established association between numerous GBA1 variants and specific neurological diseases, we extended the exploration by a phenome-wide association study to assess the impact of GBA1 variants on a wider spectrum of health-related traits. We identified 41 phenotypes associated with GBA1 variants, 39 of which were unreported, including 21 non-neurological and 20 neurological phenotypes. Based on variant-level association tests, we found beyond the neurological phenotypes particularly decreased gray-white matter contrast measures across 13 distinct brain regions, the non-coding variant rs9628662 was associated with six non-neurological traits such as hypermetropia. Another non-coding variant rs3115534 showed associations with eight biomarkers of multiple categories, and an increased risk of benign digestive neoplasms. Notably, compared to protein-coding variant p.T408M, the rs3115534 had opposing effects on three hematological biomarkers. Additionally, gene-level association analyses revealed significant associations with three neurological diseases including Parkinson's disease. The findings demonstrated that GBA1 variants significantly impact various health-related traits.</p>
16 Authors
- Jiaqi Yang
- Yuanfeng Huang
- Zheng Wang
- Shiyu Zhang
- Dai Wu
- Jiayi Xiong
- Heng Wu
- Yijing Wang
- Qiao Zhou
- Yixiao Zhu
- Guihu Zhao
- Bin Li
- Jifeng Guo
- Kun Xia
- Beisha Tang
- Jinchen Li
Enabling scientific discoveries that improve human health