Citations 5
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
Genetically Elevated LDL Associates with Lower Risk of Intracerebral Hemorrhage
Falcone, Guido J. , Kirsch, Elayna , Noche, Rommell B. , Leasure, Audrey C. , Marini, Sandro , Chung, Jaeyoon , Meschia, James F. , Brown, Devin L. , Worrall, Bradford B. , Tirschwell, David , Jagiełła, Jeremiasz , Schmidt, Helena , Jiménez-Conde, Jordi , Lindgren, Arne, Słowik, Agnieszka , Gill, Dipender , Petersen, Nils , Matouk, Charles N., Bennett, Derrick , Sun, Luan L., Clarke, Robert , Biffi, Alessandro , Kathiresan, Sekar , Langefeld, Carl D. , Woo, Daniel , Anderson, Christopher D. , James, Michael L. , Leasure, Audrey , Meschia, James F , Biffi, Alessandro , Acosta, Julián , Selim, Magdy H. , Fernández‐Cadenas, Israel , Lindgren, Arne, Holmes, Michael Vaclav , Phuah, Chia‐Ling , Matouk, Charles , Günel, Murat , Sansing, Lauren H , Chen, Zhengming , Walters, Robin G. , Gill, Thomas M. , Rosand, Jonathan M. , Sheth, Kevin N.
Annals of Neurology | April 11, 2020 | Volume: 88 | Issue: 1 | Pages: 56-66
ObjectiveObservational studies point to an inverse correlation between low‐density lipoprotein (LDL) cholesterol levels and risk of intracerebral hemorrhage (ICH), but it remains unclear whether this association is causal. We tested the hypothesis that genetically elevated LDL is associated with reduced risk of ICH.MethodsWe constructed one polygenic risk score (PRS) per lipid trait (total cholesterol, LDL, high‐density lipoprotein [HDL], and triglycerides) using independent genomewide significant single nucleotide polymorphisms (SNPs) for each trait. We used data from 316,428 individuals enrolled in the UK Biobank to estimate the effect of each PRS on its corresponding trait, and data from 1,286 ICH cases and 1,261 matched controls to estimate the effect of each PRS on ICH risk. We used these estimates to conduct Mendelian Randomization (MR) analyses.ResultsWe identified 410, 339, 393, and 317 lipid‐related SNPs for total cholesterol, LDL, HDL, and triglycerides, respectively. All four PRSs were strongly associated with their corresponding trait (all p < 1.00 × 10‐100). While one SD increase in the PRSs for total cholesterol (odds ratio [OR] = 0.92; 95% confidence interval [CI] = 0.85–0.99; p = 0.03) and LDL cholesterol (OR = 0.88; 95% CI = 0.81–0.95; p = 0.002) were inversely associated with ICH risk, no significant associations were found for HDL and triglycerides (both p > 0.05). MR analyses indicated that 1mmol/L (38.67mg/dL) increase of genetically instrumented total and LDL cholesterol were associated with 23% (OR = 0.77; 95% CI = 0.65–0.98; p = 0.03) and 41% lower risks of ICH (OR = 0.59; 95% CI = 0.42–0.82; p = 0.002), respectively.InterpretationGenetically elevated LDL levels were associated with lower risk of ICH, providing support for a potential causal role of LDL cholesterol in ICH. ANN NEUROL 2020 ANN NEUROL 2020;88:56–66
Genome-wide association study of cerebral small vessel disease reveals established and novel loci
Chung, Jaeyoon , Marini, Sandro , Pera, Joanna, Norrving, Bo, Jiménez-Conde, Jordi , Roquer, Jaume, Tirschwell, David L, Brown, Devin L. , Silliman, Scott, Worrall, Bradford B. , Demel, Stacie L , Greenberg, Steven M. , Słowik, Agnieszka , Lindgren, Arne, Schmidt, Reinhold , Sargurupremraj, Muralidharan , Tiedt, Steffen, Malik, Rainer, Debette, Stéphanie , Dichgans, Martin , Langefeld, Carl D. , Woo, Daniel , Anderson, Christopher D. , Tirschwell, David , Marini, Sandro , Dichgans, Martin , Debette, Stephanie , Fernández‐Cadenas, Israel , Selim, Magdy H. , Meschia, James F. , Lindgren, Arne, Traylor, Matthew , Tiedt, Steffen , Rosand, Jonathan M.
Brain | July 10, 2019 | Volume: 142 | Issue: 10 | Pages: 3176-3189
Intracerebral haemorrhage (ICH) and small vessel ischaemic stroke (SVS) are the most severe manifestations of cerebral small vessel disease. In a cross-phenotype genome-wide association analysis, Chung et al. identify two novel associations at 2q33 and 13q34 plus a previously identified locus at 1q22 for non-lobar ICH and SVS risk.
Transethnic genome‐wide scan identifies novel Alzheimer's disease loci
Jun, Gyungah , Chung, Jaeyoon , Beecham, Gary W. , Bennett, David A. , Buxbaum, Joseph D. , Byrd, Goldie S. , Carrasquillo, Minerva M., Crane, Paul K. , Cruchaga, Carlos , Jager, Philip L. De , Ertekin‐Taner, Nilüfer , Evans, Denis A., Fallin, M. Danielle, Friedland, Robert P. , Goate, Alison , Graff‐Radford, Neill R. , Hendrie, Hugh C. , Hall, Kathleen, Hamilton‐Nelson, Kara L., Kukull, Walter A. , Kunkle, Brian W. , Kuwano, Ryozo, Larson, Eric B., Martin, Eden R. , Montine, Thomas J. , Reiman, Eric M. , Reitz, Christiane, Sherva, Richard , George‐Hyslop, Peter St , Thornton, Timothy, Younkin, Steven G., Wang, Li‐San , Wendlund, Jens R., Winslow, Ashley R. , Adams, Perrie M. , Albert, Marilyn S. , Albin, Roger L. , Apostolova, Liana G. , Arnold, Steven E. , Asthana, Sanjay , Atwood, Craig , Barmada, Michjael M, Beach, Thomas G. , Bigio, Eileen H. , Bird, Thomas D., Blacker, Deborah , Bowen, James D. , Boxer, Adam, Cairns, Nigel J. , Cao, Chuanhai , Carlson, Chris , Carlsson, Cynthia M., Carney, Regina M., Carroll, Steven L. , Chui, Helena C., Clark, David G., Corneveaux, Jason J., Cribbs, David H. , DeKosky, Steven T. , Demirci, F. Yesim , Dick, Malcolm, Doody, Rachelle S., Duara, Ranjan , Faber, Kelley , Fairchild, Thomas, Fallon, Kenneth B., Farlow, Martin R. , Frosch, Matthew P. , Gearing, Marla , Geschwind, Daniel H. , Gilbert, John R., Glass, Jonathan D. , Growdon, John H., Håkonarson, Håkon , Hamilton, Ronald L. , Hardy, John , Harrell, Lindy E., Huentelman, Matthew J. , Hulette, Christine M., Jarvik, Gail P. , Jicha, Gregory A. , Jin, Lee‐Way, Karydas, Anna, Koo, Edward H. , Kowall, Neil W. , Kramer, Joel H. , LaFerla, Frank M. , Leverenz, James B. , Ge, Li , Lieberman, Andrew P. , Lin, Chiao‐Feng , Lyketsos, Constantine G. , Mack, Wendy J. , Marson, Daniel , Martiniuk, Frank , Mash, Deborah C. , Masliah, Eliezer , McCormick, Wayne C., McKee, Ann C. , Mesulam, Marsel, Miller, Carol A., Miller, Joshua W., Morris, John C. , Murrell, Jill R. , Olichney, John , Parisi, Joseph E., Partch, Amanda, Paulson, Henry L. , Peskind, Elaine R. , Petersen, Ronald , Pierce, Aimee, Poon, Wayne W. , Raj, Ashok , Raskind, Murray A. , Reisch, Joan, Ringman, John M. , Rosen, Howard J., Rosenberg, Roger N., Royall, Donald R., Sager, Mark A., Sano, Mary , Saykin, Andrew J. , Schneider, Lon S. , Smith, Amanda , Sonnen, Joshua A. , Tanzi, Rudolph E. , Thornton‐Wells, Tricia A., Trojanowski, John Q. , Troncoso, Juan C. , Vinters, Harry V. , Vonsattel, Jean Paul, Weıntraub, Sandra , Wishnek, Sarah, Woltjer, Randall L. , Wright, Clinton B., Wu, Chuang‐Kuo, Yu, Chang‐En , Yu, Lei , Haines, Jonathan L. , Mayeux, Richard , Pericak‐Vance, Margaret A. , Schellenberg, Gerard, Lunetta, Kathryn L. , Farrer, Lindsay A. , Bennett, David A. , Mez, Jesse , Barber, Robert C. , Carrasquillo, Minerva M. , Cruchaga, Carlos , Foroud, Tatiana , Hamilton‐Nelson, Kara L. , Inzelberg, Rivka , Kamboh, M. Ilyas , Kauwe, John S. K. , Logue, Mark W. , Manly, Jennifer J. , Mukherjee, Shubhabrata , Naj, Adam Christian , Sherva, Richard , Vardarajan, Badri Narayan , Barnes, Lisa L. , Becker, James T. , Boeve, Bradley F. , Burke, James R. , Carlsson, Cynthia M. , Chui, Helena C. , Crocco, Elizabeth , DeCarli, Charles , Dickson, Dennis W. , Duara, Ranjan , Ferris, Steven H. , Galasko, Douglas , Ghetti, Bernardino , Green, Robert C. , Head, Elizabeth , Honig, Lawrence S. , Huebinger, Ryan , Hyman, Bradley T. , Kaye, Jeffrey , Kim, Ronald , Lah, James J. , Levey, Allan I. , Li, Ge, López, Oscar L. , McCurry, Susan M. , McDavid, Andrew , Mesulam, Marsel M. , Miller, Bruce L. , Myers, Amanda , O’Bryant, Sid E. , Pankratz, V. Shane , Perry, William , Potter, Huntington , Quinn, Joseph F. , Reisberg, Barry , Roberson, Erik D. , Rogaeva, Ekaterina A. , Schneider, Julie A. , Seeley, William W. , Spina, Salvatore , Stern, Robert A. , Tsuang, Debby W. , Deerlin, Vivianna M. Van , Eldik, Linda J. Van , Welsh-Bohmer, Kathleen Anne , Williamson, Jennifer , Zhang, Xiaoling , Hakonarson, Hakon , Saykin, Andrew J , Leverenz, James B , Jarvik, Gail P , Paulson, Henry L , Hardy, John , Morris, John C , Goate, Alison M , Jicha, Gregory A , Sonnen, Joshua
Alzheimer's & Dementia | February 6, 2017 | Volume: 13 | Issue: 7 | Pages: 727-738
Abstract Introduction Genetic loci for Alzheimer's disease (AD) have been identified in whites of European ancestry, but the genetic architecture of AD among other populations is less understood. Methods We conducted a transethnic genome‐wide association study (GWAS) for late‐onset AD in Stage 1 sample including whites of European Ancestry, African‐Americans, Japanese, and Israeli‐Arabs assembled by the Alzheimer's Disease Genetics Consortium. Suggestive results from Stage 1 from novel loci were followed up using summarized results in the International Genomics Alzheimer's Project GWAS dataset. Results Genome‐wide significant (GWS) associations in single‐nucleotide polymorphism (SNP)–based tests ( P < 5 × 10 −8 ) were identified for SNPs in PFDN1/HBEGF , USP6NL/ECHDC3 , and BZRAP1‐AS1 and for the interaction of the (apolipoprotein E) APOE ε4 allele with NFIC SNP. We also obtained GWS evidence ( P < 2.7 × 10 −6 ) for gene‐based association in the total sample with a novel locus, TPBG ( P = 1.8 × 10 −6 ). Discussion Our findings highlight the value of transethnic studies for identifying novel AD susceptibility loci.
Two novel loci, COBL and SLC10A2, for Alzheimer's disease in African Americans
Chung, Jaeyoon , Jun, Gyungah , Kriegel, Joshua, Bourlas, Alexandra P., Sherva, Richard , Barnes, Lisa L. , Bennett, David A. , Buxbaum, Joseph D. , Byrd, Goldie S. , Crane, Paul K. , Ertekin‐Taner, Nilüfer , Evans, Denis A., Fallin, M. Daniele , Goate, Alison , Graff‐Radford, Neill R. , Hall, Kathleen, Kukull, Walter A. , Larson, Eric B., Haines, Jonathan L. , Mayeux, Richard , Pericak‐Vance, Margaret A. , Schellenberg, Gerard D. , Lunetta, Kathryn L. , Farrer, Lindsay A. , Bennett, David A. , Mez, Jesse , Sherva, Richard , Logue, Mark W. , Foroud, Tatiana , Kamboh, M. Ilyas , Manly, Jennifer J. , Goate, Alison M , Barnes, Lisa L
Alzheimer's & Dementia | October 20, 2016 | Volume: 13 | Issue: 2 | Pages: 119-129
AbstractIntroductionAfrican Americans' (AAs) late‐onset Alzheimer's disease (LOAD) genetic risk profile is incompletely understood. Including clinical covariates in genetic analyses using informed conditioning might improve study power.MethodsWe conducted a genome‐wide association study (GWAS) in AAs employing informed conditioning in 1825 LOAD cases and 3784 cognitively normal controls. We derived a posterior liability conditioned on age, sex, diabetes status, current smoking status, educational attainment, and affection status, with parameters informed by external prevalence information. We assessed association between the posterior liability and a genome‐wide set of single‐nucleotide polymorphisms (SNPs), controlling for APOE and ABCA7, identified previously in a LOAD GWAS of AAs.ResultsTwo SNPs at novel loci, rs112404845 (P = 3.8 × 10−8), upstream of COBL, and rs16961023 (P = 4.6 × 10−8), downstream of SLC10A2, obtained genome‐wide significant evidence of association with the posterior liability.DiscussionAn informed conditioning approach can detect LOAD genetic associations in AAs not identified by traditional GWAS.