Klein, Hans‐Ulrich
https://orcid.org/0000-0002-6382-9428
Mayo Clinic
Columbia University Irving Medical Center
Citations 2
Epigenomic features related to microglia are associated with attenuated effect of APOE ε4 on Alzheimer's disease risk in humans
Yu, Lei , Olah, Marta , Smith, Rebecca G. , Oatman, Stephanie R., Allen, Mariet , Pishva, Ehsan , Zhang, Bin , Ertekin‐Taner, Nilüfer , Bennett, David A. , Klein, Hans‐Ulrich , Jager, Philip L. De , Bennett, David A. , Ma, Yiyi , Menon, Vilas , Lunnon, Katie
Alzheimer's & Dementia | September 5, 2021 | Volume: 18 | Issue: 4 | Pages: 688-699
Abstract Not all apolipoprotein E ( APOE ) ε4 carriers who survive to advanced age develop Alzheimer's disease (AD); factors attenuating the risk of ε4 on AD may exist. Guided by the top ε4‐attenuating signals from methylome‐wide association analyses (N = 572, ε4+ and ε4–) of neurofibrillary tangles and neuritic plaques, we conducted a meta‐analysis for pathological AD within the ε4+ subgroups (N = 235) across four independent collections of brains. Cortical RNA‐seq and microglial morphology measurements were used in functional analyses. Three out of the four significant CpG dinucleotides were captured by one principal component (PC1), which interacts with ε4 on AD, and is associated with expression of innate immune genes and activated microglia. In ε4 carriers, reduction in each unit of PC1 attenuated the odds of AD by 58% (odds ratio = 2.39, 95% confidence interval = [1.64,3.46], P = 7.08 × 10 –6 ). An epigenomic factor associated with a reduced proportion of activated microglia (epigenomic factor of activated microglia, EFAM) appears to attenuate the risk of ε4 on AD.
Novel Alzheimer Disease Risk Loci and Pathways in African American Individuals Using the African Genome Resources Panel
Kunkle, Brian W. , Schmidt, Michael A. , Klein, Hans‐Ulrich , Hamilton‐Nelson, Kara L., Larson, Eric B., Evans, Denis A., Jager, Phil L. De, Crane, Paul K. , Buxbaum, Joseph D. , Ertekin‐Taner, Nilüfer , Barnes, Lisa L. , Fallin, M. Daniele , Go, Rodney C.P., Obisesan, Thomas O. , Bennett, David A. , Hall, Kathleen, Goate, Alison , Foroud, Tatiana M., Martin, Eden R. , Wang, Li‐San , Byrd, Goldie S. , Haines, Jonathan L. , Schellenberg, Gerard D., Mayeux, Richard , Pericak‐Vance, Margaret A. , Reitz, Christiane, Perrie, M. Adams, Roger, L. Albin, Liana, G Apostolova, Steven, Eschrich, Craig, S , Clinton, T. Baldwin, Robert, C. Barber, Barral, Sandra, Thomas, Gunther, James, T., Gary, W. Beecham, Eileen, H. Bigio, Thomas, D., Blacker, Deborah, Bradley, F. Boeve, James, D. Bowen, Boxer, Adam, James, R. Burke, Jeffrey, Morris, Nigel, J Cairns, Cynthia, M. Carlsson, Regina, M. Carney, Minerva, M. Carrasquillo, David, Hugh-Jones, Dick, Malcom, Dickson, Dennis, W., Doody, Rachelle S., Duara, Ranjan , Kelley, M. Faber, Thomas, Jaya , Kenneth, B., David, W. Fardo, Martin, Roger, Matthew, P. Frosch, Douglas, R. Galasko, Gearing, Marla , Daniel, Hervé, Gilbert, John, R., Robert, C. Green, John, Harding, Ronald, L. Hamilton, Hardy, John , Lindy, E. Harrell, Lawrence, Steve, Ryan, Mary, Matthew, J. Huentelman, Christine, M Hulette, Gail, P. Jarvik, Jin, Lee‐Way, Karydas, Anna, Mindy, J. Katz, John, S., Joel, H. Kramer, James, J. Lah, Andrew, Peter, Richard, B., Constantine, G. Lyketsos, Malamon, John , Daniel, Chammiran , Martiniuk, Frank , Masliah, Eliezer , Wayne, C. McCormick, Susan, M, Andrew, Nesbit M, McDonough, Stefan, Ann., Canfield, Mesulam, Marsel, Bruce, L. Miller, Carol, A. Miller, Thomas, J. Montine, Amanda, J. Myers, John, M. Olichney, Joseph, E. Parisi, Peskind, Elaine R. , Pierce, Aimee, Wayne, W. Poon, Joseph, F. Quinn, Raj, Ashok , Raskind, Murray A. , Reisch, Joan, S., John, M. Ringman, Erik, D. Roberson, Howard, J. Rosen, Donald, R. Royall, Mark, A. Sager, Julie, A. Schneider, Lon, Su, William, W. Seeley, Small, Scott A. , Sonnen, Joshua, A., Robert, Aiko, Rudolph, E. Tanzi, Juan, Caballero, Debby, W. Tsuang, Vivianna, M. Van Deerlin, Badri, Nabeel, Harry, Vanessa, Vonsattel, Jean Paul, Weıntraub, Sandra , Kathleen, A Welsh-Bohmer, Kirk, C W, Thomas, SubinVarghese, Randall, Linnell B., Wu, Chuang‐Kuo, Steven, G. Younkin, Yu, Lei , Yu, Chang‐En , Graff‐Radford, Neill R. , Martinez, Izri, Ayodele, Temitope , Cantwell, Laura B., Jean‐Francois, Melissa, Kuzma, Amanda , Adams, Lonnie D., Chung, Jaeyoon , Jun, Gyungah , Hendrie, Hugh C. , Reiman, Eric M. , Kowall, Neil W. , Golde, Todd E. , Saykin, Andrew J. , Starks, Takiyah D. , Albert, Marilyn S. , Petersen, Ronald , Sano, Mary , Wısnıewskı, Thomas , Vassar, Robert , Kaye, Jeffrey A., Henderson, Victor W. , DeCarli, Charles , LaFerla, Frank M. , Brewer, James B., Miller, Bruce L. , Swerdlow, Russell H. , Paulson, Henry L. , Trojanowski, John Q. , Chui, Helena C., Rosenberg, Roger N., Craft, Suzanne , Grabowski, Thomas J. , Asthana, Sanjay , Morris, John C. , Strittmatter, Stephen M. , Kukull, Walter A. , Asthana, Sanjay , Jarvik, Gail P. , Cribbs, David H. , Sonnen, Joshua A. , Bennett, David A. , Saykin, Andrew J , Miller, Bruce L , Jarvik, Gail P , Paulson, Henry L , Hardy, John , Morris, John C , Goate, Alison M , Sonnen, Joshua , Barnes, Lisa L , Naj, Adam Christian , Hamilton‐Nelson, Kara L. , Manly, Jennifer J. , Kamboh, M. Ilyas , Farrer, Lindsay A. , Abner, Erin L. , Atwood, Craig, S., Becker, James, T., Eileen, H Bigio, Blacker, Deborah , Cao, Chuanhai , Cruchaga, Carlos , Dickson, Dennis, W., Duara, Ranjan , David, W. Fardo, Farlow, Martin, R., Ferris, Steven H. , Geschwind, Daniel, H., Ghetti, Bernardino , Gilbert, John, R., Håkonarson, Håkon , Honig, Lawrence, S., Huebinger, Ryan, M., Matthew, J Huentelman, Kauwe, John, S.K., Keene, C. Dirk , Kim, Ronald, Leung, Yuk Yee , Li, Ge , Lipton, Richard, B., Marson, Daniel, C., McDavid, Andrew, N., Mesulam, Marsel M. , Bruce, L Miller, Mukherjee, Shubhabrata , O’Bryant, Sid, E., Potter, Huntington , Qu, Liming , Raj, Ashok, Reisberg, Barry , Reisch, Joan, S., Rogaeva, Ekaterina A. , Julie, A Schneider, Schneider, Lon, S., William, W Seeley, Spina, Salvatore , George‐Hyslop, Peter St , Valladares, Otto , Vardarajan, Badri, N., Wilhelmsen, Kirk, C., Williamson, Jennifer , Wingo, Thomas, S., Woltjer, Randall, L., Steven, G Younkin, Zhao, Yi Chen , Logue, Mark W. , Adams, L.D., Vance, Jeffery M. , Cuccaro, Michael L. , Mez, Jesse , Lunetta, Kathryn L. , López, Oscar L. , Leverenz, James B. , Levey, Allan I. , Hyman, Bradley T. , Kaye, Jeffrey A., Eldik, Linda J. Van , Chui, Helena C.
JAMA Neurology | October 19, 2020 | Volume: 78 | Issue: 1 | Pages: 102