TY - JOUR T1 - Aging shapes the population-mean and -dispersion of gene expression in human brains JF - bioRxiv DO - 10.1101/039933 SP - 039933 AU - Candice L. Brinkmeyer-Langford AU - Jinting Guan AU - Guoli Ji AU - James J. Cai Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/02/20/039933.abstract N2 - Human aging is associated with cognitive decline and an increased risk of neurodegenerative disease. We assessed age-related brain gene expression by analyzing the Genotype-Tissue Expression (GTEx) data from 2,522 tissue samples across 13 brain regions in 169 donors of European descent aged between 20 and 70 years. After controlling for covariates and hidden confounding factors, we identified 1,446 protein-coding genes whose expression in one or more brain regions is correlated or anti-correlated with chronological age at a false discovery rate of 5%. These genes are involved in various biological processes including apoptosis, mRNA splicing, amino acid biosynthesis, and neurotransmitter transport. The distribution of these genes among brain regions is markedly uneven, suggesting a variable brain region-specific response to aging. The aging response of many genes, e.g., TP37 and C1QA, is dependent on individuals’ genotypic backgrounds. Finally, using dispersion-specific analysis, we identified genes, e.g., IL7R, MS4A4E, and TERF1/TERF2, whose expression is differentially dispersed by aging, i.e., variances differ between age groups. Our results demonstrate that age-related gene expression is brain region-specific, genotype-dependent, and associated with both mean and dispersion changes. Our findings provide a foundation for more sophisticated gene expression modeling in the studies of age-related neurodegenerative diseases. ER -