RT Journal Article
SR Electronic
T1 Identification of novel Alzheimer’s disease genes co-expressed with <em>TREM2</em>
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.11.13.381640
DO 10.1101/2020.11.13.381640
A1 Reddy, Joseph S.
A1 Allen, Mariet
A1 Wang, Xue
A1 Biernacka, Joanna M.
A1 Coombes, Brandon J.
A1 Jenkins, Gregory D.
A1 Sinnwell, Jason P.
A1 Carrasquillo, Minerva M.
A1 Pottier, Cyril P.
A1 Ren, Yingxue
A1 Sarangi, Vivekananda
A1 Younkin, Curtis S.
A1 Asmann, Yan W.
A1 Ross, Owen A.
A1 Rademakers, Rosa
A1 Golde, Todd E.
A1 Ertekin-Taner, Nilüfer
A1 Younkin, Steven G.
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.