RT Journal Article SR Electronic T1 Identification of novel Alzheimer’s disease genes co-expressed with TREM2 JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.11.13.381640 DO 10.1101/2020.11.13.381640 A1 Joseph S. Reddy A1 Mariet Allen A1 Xue Wang A1 Joanna M. Biernacka A1 Brandon J. Coombes A1 Gregory D. Jenkins A1 Jason P. Sinnwell A1 Minerva M. Carrasquillo A1 Cyril P. Pottier A1 Yingxue Ren A1 Vivekananda Sarangi A1 Curtis S. Younkin A1 Yan W. Asmann A1 Owen A. Ross A1 Rosa Rademakers A1 Todd E. Golde A1 Nilüfer Ertekin-Taner A1 Steven G. Younkin YR 2020 UL http://biorxiv.org/content/early/2020/11/15/2020.11.13.381640.abstract AB By analyzing whole-exome data from the Alzheimer’s disease sequencing project (ADSP), we identify a set of 4 genes that show highly significant association with Alzheimer’s disease (AD). These genes were identified within a human TREM2 co-expression network using a novel approach wherein prioritized polygenic score analyses were performed sequentially to identify significant polygenic components. Two of the 4 genes (TREM2, RIN3) have previously been linked to AD and two (ATP8B4, IL17RA) are novel. Like TREM2, the 2 novel AD genes are selectively expressed in human microglial cells. The most significant variants in ATP8B4 and IL17RA are non-synonymous variants with strong effects comparable to the APOE ε4 and ε2 alleles. These protein-altering variants will provide unique opportunities to further explore the biological role of microglial cells in AD and help inform future immune modulatory therapeutic development for AD.Competing Interest StatementThe authors have declared no competing interest.