한빛사논문
- 조회233
Samuel S. Kim 1,2,*, Buu Truong 2,3,8,*, Karthik Jagadeesh 2,8, Kushal K. Dey 2,4,8, Amber Z. Shen 5, Soumya Raychaudhuri 6, Manolis Kellis 1 & Alkes L. Price 1,2,3,7,*
1Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, UK.
2Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, UK.
3Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, UK.
4Computational and Systems Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
5Department of Mathematics, Massachusetts Institute of Technology, Cambridge, MA, USA.
6Division of Genetics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA.
7Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
8These authors contributed equally: Buu Truong, Karthik Jagadeesh, Kushal K. Dey.
*Corresponding authors: correspondence to Samuel S. Kim, Manolis Kellis or Alkes L. Price
Abstract
Prioritizing disease-critical cell types by integrating genome-wide association studies (GWAS) with functional data is a fundamental goal. Single-cell chromatin accessibility (scATAC-seq) and gene expression (scRNA-seq) have characterized cell types at high resolution, and studies integrating GWAS with scRNA-seq have shown promise, but studies integrating GWAS with scATAC-seq have been limited. Here, we identify disease-critical fetal and adult brain cell types by integrating GWAS summary statistics from 28 brain-related diseases/traits (average N = 298 K) with 3.2 million scATAC-seq and scRNA-seq profiles from 83 cell types. We identified disease-critical fetal (respectively adult) brain cell types for 22 (respectively 23) of 28 traits using scATAC-seq, and for 8 (respectively 17) of 28 traits using scRNA-seq. Significant scATAC-seq enrichments included fetal photoreceptor cells for major depressive disorder, fetal ganglion cells for BMI, fetal astrocytes for ADHD, and adult VGLUT2 excitatory neurons for schizophrenia. Our findings improve our understanding of brain-related diseases/traits and inform future analyses.
논문정보
- Research article
- 2024년 01월 (BRIC 등록일 2024-03-15)
- 국외 연구진
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