疾病
神经退行性变
生物
表型
免疫系统
基因
全基因组关联研究
T细胞
遗传学
免疫学
生物信息学
医学
内科学
单核苷酸多态性
基因型
作者
Dallin Dressman,Shinya Tasaki,Lei Yu,Julie A. Schneider,David A. Bennett,Wassim Elyaman,Badri N. Vardarajan
标识
DOI:10.3389/fimmu.2024.1337831
摘要
Introduction T cells, known for their ability to respond to an enormous variety of pathogens and other insults, are increasingly recognized as important mediators of pathology in neurodegeneration and other diseases. T cell gene expression phenotypes can be regulated by disease-associated genetic variants. Many complex diseases are better represented by polygenic risk than by individual variants. Methods We first compute a polygenic risk score (PRS) for Alzheimer’s disease (AD) using genomic sequencing data from a cohort of Alzheimer’s disease (AD) patients and age-matched controls, and validate the AD PRS against clinical metrics in our cohort. We then calculate the PRS for several autoimmune disease, neurological disorder, and immune function traits, and correlate these PRSs with T cell gene expression data from our cohort. We compare PRS-associated genes across traits and four T cell subtypes. Results Several genes and biological pathways associated with the PRS for these traits relate to key T cell functions. The PRS-associated gene signature generally correlates positively for traits within a particular category (autoimmune disease, neurological disease, immune function) with the exception of stroke. The trait-associated gene expression signature for autoimmune disease traits was polarized towards CD4+ T cell subtypes. Discussion Our findings show that polygenic risk for complex disease and immune function traits can have varying effects on T cell gene expression trends. Several PRS-associated genes are potential candidates for therapeutic modulation in T cells, and could be tested in in vitro applications using cells from patients bearing high or low polygenic risk for AD or other conditions.
科研通智能强力驱动
Strongly Powered by AbleSci AI