Common protein-altering variant in GFAP is associated with white matter lesions in the older Japanese population
The genetic architecture of white matter lesions (WMLs) in Asian populations has not been well-characterized. Here, we performed a genome-wide association study (GWAS) to identify loci associated with the WML volume. Brain MRI and DNA samples were collected from 9479 participants in the Japan Prospective Studies Collaboration for Aging and Dementia (JPSC-AD). The GWAS confirmed three known WML-associated loci (SH3PXD2A, GFAP, and TRIM47). The lead variant of GFAP was a common missense variant (p.D295N) in East Asians. Meta-GWAS using the publicly available summary statistics of UK Biobank identified one previously unreported locus 6q23.2 (SLC2A12). Integration with expression quantitative trait locus data implied the newly identified locus affects SLC2A12 expression. The effect sizes of 20 lead variants at the WML-associated loci were moderately correlated between JPSC-AD and UK Biobank. These results indicate that the alteration in GFAP protein caused by the common missense variant in East Asians influences the WML volume.
Authors
- Kenjiro Ono (ORCID: https://orcid.org/0000-0001-8454-6155)
- Yukihide Momozawa (ORCID: https://orcid.org/0000-0001-5638-3504)
- Chikashi C. Terao (ORCID: https://orcid.org/0000-0002-6452-4095)
- Tomoyuki Ohara (ORCID: https://orcid.org/0000-0002-8116-4730)
- Yoshihiko Furuta (ORCID: https://orcid.org/0000-0003-2373-9636)
- Masato Akiyama (ORCID: https://orcid.org/0000-0002-1879-5476)
- Yasuyuki Taki
- Jun Hata (ORCID: https://orcid.org/0000-0003-2698-344X)
- Masaru Mimura (ORCID: https://orcid.org/0000-0002-3874-5273)
- Mao Shibata (ORCID: https://orcid.org/0000-0002-4468-6214)
- Naoki Hirabayashi (ORCID: https://orcid.org/0000-0002-2028-4261)
- Jun‐ichi Iga (ORCID: https://orcid.org/0000-0003-4409-3096)
- Yasuko Tatewaki
- Minoru Takebayashi (ORCID: https://orcid.org/0000-0001-9962-8444)
- Toshiharu Ninomiya (ORCID: https://orcid.org/0000-0003-1345-9032)
- Takanori Honda (ORCID: https://orcid.org/0000-0002-1011-9879)
- Tetsuya Maeda (ORCID: https://orcid.org/0000-0002-6207-8343)
- Shigeyuki Nakaji (ORCID: https://orcid.org/0000-0001-8445-8606)
- Kenji Nakashima
Institutions
- Kanazawa University (JP)
- Kyushu University (JP)
- Hirosaki University (JP)
- University of Shizuoka (JP)
- Iwate Medical University (JP)
- Tohoku University (JP)
- Keio University (JP)
- National Kyushu Medical Center (JP)
- Shizuoka General Hospital (JP)
- National Hospital Organization (JP)
- RIKEN Center for Integrative Medical Sciences (JP)
- Ehime University (JP)
- Kumamoto University (JP)
Publication Details
- Journal
- npj Genomic Medicine
- Published
- 2024-11-13
- DOI
- https://doi.org/10.1038/s41525-024-00431-x
- Citations
- 2
- Primary Topic
- RNA regulation and disease
- Type
- article
- Field-Weighted Citation Impact
- 0.47