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1. Whole genome‐wide sequence analysis of long‐lived families (Long‐Life Family Study) identifies MTUS2 gene associated with late‐onset Alzheimer's disease

Author: Xicota, Laura, Cosentino, Stephanie, Vardarajan, Badri, Mayeux, Richard, Perls, Thomas T, Andersen, Stacy L, Zmuda, Joseph M, Thyagarajan, Bharat, Yashin, Anatoli, Wojczynski, Mary K, Krinsky‐McHale, Sharon, Handen, Benjamin L, Christian, Bradley T, Head, Elizabeth, Mapstone, Mark E, Schupf, Nicole, Lee, Joseph H, Barral, Sandra, Study, the Long‐Life Family, Abner, Erin, Adams, Perrie M, Aguirre, Alyssa, Albert, Marilyn S, Albin, Roger L, Allen, Mariet, Alvarez, Lisa, Andrews, Howard, Apostolova, Liana G, Arnold, Steven E, Asthana, Sanjay, Atwood, Craig S, Ayres, Gayle, Barber, Robert C, Barnes, Lisa L, Bartlett, Jackie, Beach, Thomas G, Becker, James T, Beecham, Gary W, Benchek, Penelope, Bennett, David A, Bertelson, John, Biber, Sarah A, Bird, Thomas D, Blacker, Deborah, Boeve, Bradley F, Bowen, James D, Boxer, Adam, Brewer, James B, Burke, James R, Burns, Jeffrey M, Bush, William S, Buxbaum, Joseph D, Byrd, Goldie, Cantwell, Laura B, Cao, Chuanhai, Carlsson, Cynthia M, Carrasquillo, Minerva M, Chan, Kwun C, Chasse, Scott, Chen, Yen‐Chi, Chesselet, Marie‐Francoise, Chin, Nathaniel A, Chui, Helena C, Chung, Jaeyoon, Craft, Suzanne, Crane, Paul K, Cranney, Marissa, Cruchaga, Carlos, Cuccaro, Michael L, Culhane, Jessica, Cullum, C Munro, Darby, Eveleen, Davis, Barbara, De Jager, Philip L, DeCarli, Charles, DeToledo, John C, Dickson, Dennis W, Dobbins, Nic, Duara, Ranjan, Ertekin‐Taner, Nilufer, Evans, Denis A, Faber, Kelley M, Fairchild, Thomas J, Fallin, Daniele, Fallon, Kenneth B, Fardo, David W, Farlow, Martin R, Farrell, John, Farrer, Lindsay A, Fernandez‐Hernandez, Victoria, Foroud, Tatiana M, Frosch, Matthew P, Galasko, Douglas R, Gamboa, Adriana, Gauthreaux, Kathryn M, Gefen, Tamar, Geschwind, Daniel H, Ghetti, Bernardino, and Gilbert, John R
Subjects: Biomedical and Clinical Sciences, Biological Psychology, Clinical Sciences, Neurosciences, Psychology, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Acquired Cognitive Impairment, Neurodegenerative, Brain Disorders, Dementia, Alzheimer's Disease, Human Genome, Biotechnology, Aging, Genetics, 2.1 Biological and endogenous factors, Aetiology, Neurological, Humans, Alzheimer Disease, Amyloid beta-Peptides, Genetic Predisposition to Disease, Genome-Wide Association Study, Microtubule-Associated Proteins, Polymorphism, Single Nucleotide, Sequence Analysis, genetic risk, late-onset Alzheimer's disease, microtubule protein, MTUS2 gene, whole genome sequence, Long‐Life Family Study, Alzheimer's Disease Genetic Consortium, Alzheimer's Biomarkers Consortium‐Down Syndrome, late‐onset Alzheimer's disease, Geriatrics, Clinical sciences, Biological psychology
Abstract: IntroductionLate-onset Alzheimer's disease (LOAD) has a strong genetic component. Participants in Long-Life Family Study (LLFS) exhibit delayed onset of dementia, offering a unique opportunity to investigate LOAD genetics.MethodsWe conducted a whole genome sequence analysis of 3475 LLFS members. Genetic associations were examined in six independent studies (N = 14,260) with a wide range of LOAD risk. Association analysis in a sub-sample of the LLFS cohort (N = 1739) evaluated the association of LOAD variants with beta amyloid (Aβ) levels.ResultsWe identified several single nucleotide polymorphisms (SNPs) in tight linkage disequilibrium within the MTUS2 gene associated with LOAD (rs73154407, p = 7.6 × 10-9). Association of MTUS2 variants with LOAD was observed in the five independent studies and was significantly stronger within high levels of Aβ42/40 ratio compared to lower amyloid.DiscussionMTUS2 encodes a microtubule associated protein implicated in the development and function of the nervous system, making it a plausible candidate to investigate LOAD biology.HighlightsLong-Life Family Study (LLFS) families may harbor late onset Alzheimer's dementia (LOAD) variants. LLFS whole genome sequence analysis identified MTUS2 gene variants associated with LOAD. The observed LLFS variants generalized to cohorts with wide range of LOAD risk. The association of MTUS2 with LOAD was stronger within high levels of beta amyloid. Our results provide evidence for MTUS2 gene as a novel LOAD candidate locus.
Published: 2024

2. Exome sequencing identifies rare damaging variants in ATP8B4 and ABCA1 as risk factors for Alzheimer’s disease

Author: Holstege, Henne, Hulsman, Marc, Charbonnier, Camille, Grenier-Boley, Benjamin, Quenez, Olivier, Grozeva, Detelina, van Rooij, Jeroen GJ, Sims, Rebecca, Ahmad, Shahzad, Amin, Najaf, Norsworthy, Penny J, Dols-Icardo, Oriol, Hummerich, Holger, Kawalia, Amit, Amouyel, Philippe, Beecham, Gary W, Berr, Claudine, Bis, Joshua C, Boland, Anne, Bossù, Paola, Bouwman, Femke, Bras, Jose, Campion, Dominique, Cochran, J Nicholas, Daniele, Antonio, Dartigues, Jean-François, Debette, Stéphanie, Deleuze, Jean-François, Denning, Nicola, DeStefano, Anita L, Farrer, Lindsay A, Fernández, Maria Victoria, Fox, Nick C, Galimberti, Daniela, Genin, Emmanuelle, Gille, Johan JP, Le Guen, Yann, Guerreiro, Rita, Haines, Jonathan L, Holmes, Clive, Ikram, M Arfan, Ikram, M Kamran, Jansen, Iris E, Kraaij, Robert, Lathrop, Marc, Lemstra, Afina W, Lleó, Alberto, Luckcuck, Lauren, Mannens, Marcel MAM, Marshall, Rachel, Martin, Eden R, Masullo, Carlo, Mayeux, Richard, Mecocci, Patrizia, Meggy, Alun, Mol, Merel O, Morgan, Kevin, Myers, Richard M, Nacmias, Benedetta, Naj, Adam C, Napolioni, Valerio, Pasquier, Florence, Pastor, Pau, Pericak-Vance, Margaret A, Raybould, Rachel, Redon, Richard, Reinders, Marcel JT, Richard, Anne-Claire, Riedel-Heller, Steffi G, Rivadeneira, Fernando, Rousseau, Stéphane, Ryan, Natalie S, Saad, Salha, Sanchez-Juan, Pascual, Schellenberg, Gerard D, Scheltens, Philip, Schott, Jonathan M, Seripa, Davide, Seshadri, Sudha, Sie, Daoud, Sistermans, Erik A, Sorbi, Sandro, van Spaendonk, Resie, Spalletta, Gianfranco, Tesi, Niccolo’, Tijms, Betty, Uitterlinden, André G, van der Lee, Sven J, Visser, Pieter Jelle, Wagner, Michael, Wallon, David, Wang, Li-San, Zarea, Aline, Clarimon, Jordi, van Swieten, John C, Greicius, Michael D, Yokoyama, Jennifer S, Cruchaga, Carlos, Hardy, John, and Ramirez, Alfredo
Subjects: Biological Sciences, Genetics, Dementia, Alzheimer's Disease, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Human Genome, Prevention, Acquired Cognitive Impairment, Neurodegenerative, Aging, Clinical Research, Biotechnology, Brain Disorders, 2.1 Biological and endogenous factors, Aetiology, Neurological, Humans, Adenosine Triphosphatases, Alzheimer Disease, ATP Binding Cassette Transporter 1, Genome-Wide Association Study, Risk Factors, Exosomes, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract: Alzheimer's disease (AD), the leading cause of dementia, has an estimated heritability of approximately 70%1. The genetic component of AD has been mainly assessed using genome-wide association studies, which do not capture the risk contributed by rare variants2. Here, we compared the gene-based burden of rare damaging variants in exome sequencing data from 32,558 individuals-16,036 AD cases and 16,522 controls. Next to variants in TREM2, SORL1 and ABCA7, we observed a significant association of rare, predicted damaging variants in ATP8B4 and ABCA1 with AD risk, and a suggestive signal in ADAM10. Additionally, the rare-variant burden in RIN3, CLU, ZCWPW1 and ACE highlighted these genes as potential drivers of respective AD-genome-wide association study loci. Variants associated with the strongest effect on AD risk, in particular loss-of-function variants, are enriched in early-onset AD cases. Our results provide additional evidence for a major role for amyloid-β precursor protein processing, amyloid-β aggregation, lipid metabolism and microglial function in AD.
Published: 2022

3. Ancestral risk modification for multiple sclerosis susceptibility detected across the Major Histocompatibility Complex in a multi-ethnic population

Author: Beecham, Ashley H, Amezcua, Lilyana, Chinea, Angel, Manrique, Clara P, Gomez, Lissette, Martinez, Andrea, Beecham, Gary W, Patsopoulos, Nikolaos A, Chitnis, Tanuja, Weiner, Howard L, De Jager, Philip L, Burchard, Esteban G, Lund, Brett T, Fitzgerald, Kathryn C, Calabresi, Peter A, Delgado, Silvia R, Oksenberg, Jorge R, and McCauley, Jacob L
Subjects: Biological Sciences, Biomedical and Clinical Sciences, Genetics, Clinical Research, Neurodegenerative, Autoimmune Disease, Neurosciences, Brain Disorders, Prevention, Human Genome, Multiple Sclerosis, 2.1 Biological and endogenous factors, Aetiology, Humans, Alleles, Gene Frequency, Genetic Predisposition to Disease, Haplotypes, HLA-DRB1 Chains, Linkage Disequilibrium, Major Histocompatibility Complex, Risk, European People, African People, General Science & Technology
Abstract: The Major Histocompatibility Complex (MHC) makes the largest genetic contribution to multiple sclerosis (MS) susceptibility, with 32 independent effects across the region explaining 20% of the heritability in European populations. Variation is high across populations with allele frequency differences and population-specific risk alleles identified. We sought to identify MHC-specific MS susceptibility variants and assess the effect of ancestral risk modification within 2652 Latinx and Hispanic individuals as well as 2435 Black and African American individuals. We have identified several novel susceptibility alleles which are rare in European populations including HLA-B*53:01, and we have utilized the differing linkage disequilibrium patterns inherent to these populations to identify an independent role for HLA-DRB1*15:01 and HLA-DQB1*06:02 on MS risk. We found a decrease in Native American ancestry in MS cases vs controls across the MHC, peaking near the previously identified MICB locus with a decrease of ~5.5% in Hispanics and ~0.4% in African Americans. We have identified several susceptibility variants, including within the MICB gene region, which show global ancestry risk modification and indicate ancestral differences which may be due in part to correlated environmental factors. We have also identified several susceptibility variants for which MS risk is modified by local ancestry and indicate true ancestral genetic differences; including HLA-DQB1*06:02 for which MS risk for European allele carriers is almost two times the risk for African allele carriers. These results validate the importance of investigating MS susceptibility at an ancestral level and offer insight into the epidemiology of MS phenotypic diversity.
Published: 2022

4. Genetic analyses in multiplex families confirms chromosome 5q35 as a risk locus for Alzheimer’s Disease in individuals of African Ancestry

Author: Nuytemans, Karen, Rajabli, Farid, Jean-Francois, Melissa, Kurup, Jiji Thulaseedhara, Adams, Larry D., Starks, Takiyah D., Whitehead, Patrice L., Kunkle, Brian W., Caban-Holt, Allison, Haines, Jonathan L., Cuccaro, Michael L., Vance, Jeffery M., Byrd, Goldie S., Beecham, Gary W., Reitz, Christiane, and Pericak-Vance, Margaret A.
Published: 2024
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5. Genomewide Association Studies of LRRK2 Modifiers of Parkinson's Disease

Author: Lai, Dongbing, Alipanahi, Babak, Fontanillas, Pierre, Schwantes‐An, Tae‐Hwi, Aasly, Jan, Alcalay, Roy N, Beecham, Gary W, Berg, Daniela, Bressman, Susan, Brice, Alexis, Brockman, Kathrin, Clark, Lorraine, Cookson, Mark, Das, Sayantan, Van Deerlin, Vivianna, Follett, Jordan, Farrer, Matthew J, Trinh, Joanne, Gasser, Thomas, Goldwurm, Stefano, Gustavsson, Emil, Klein, Christine, Lang, Anthony E, Langston, J William, Latourelle, Jeanne, Lynch, Timothy, Marder, Karen, Marras, Connie, Martin, Eden R, McLean, Cory Y, Mejia‐Santana, Helen, Molho, Eric, Myers, Richard H, Nuytemans, Karen, Ozelius, Laurie, Payami, Haydeh, Raymond, Deborah, Rogaeva, Ekaterina, Rogers, Michael P, Ross, Owen A, Samii, Ali, Saunders‐Pullman, Rachel, Schüle, Birgitt, Schulte, Claudia, Scott, William K, Tanner, Caroline, Tolosa, Eduardo, Tomkins, James E, Vilas, Dolores, Trojanowski, John Q, Team, The 23andMe Research, Uitti, Ryan, Vance, Jeffery M, Visanji, Naomi P, Wszolek, Zbigniew K, Zabetian, Cyrus P, Mirelman, Anat, Giladi, Nir, Urtreger, Avi Orr, Cannon, Paul, Fiske, Brian, and Foroud, Tatiana
Subjects: Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Aging, Genetics, Brain Disorders, Prevention, Parkinson's Disease, Neurodegenerative, Human Genome, Aetiology, 2.1 Biological and endogenous factors, Neurological, Aged, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2, Male, Middle Aged, Mutation, Parkinson Disease, Penetrance, 23andMe Research Team, Neurology & Neurosurgery, Clinical sciences
Abstract: ObjectiveThe aim of this study was to search for genes/variants that modify the effect of LRRK2 mutations in terms of penetrance and age-at-onset of Parkinson's disease.MethodsWe performed the first genomewide association study of penetrance and age-at-onset of Parkinson's disease in LRRK2 mutation carriers (776 cases and 1,103 non-cases at their last evaluation). Cox proportional hazard models and linear mixed models were used to identify modifiers of penetrance and age-at-onset of LRRK2 mutations, respectively. We also investigated whether a polygenic risk score derived from a published genomewide association study of Parkinson's disease was able to explain variability in penetrance and age-at-onset in LRRK2 mutation carriers.ResultsA variant located in the intronic region of CORO1C on chromosome 12 (rs77395454; p value = 2.5E-08, beta = 1.27, SE = 0.23, risk allele: C) met genomewide significance for the penetrance model. Co-immunoprecipitation analyses of LRRK2 and CORO1C supported an interaction between these 2 proteins. A region on chromosome 3, within a previously reported linkage peak for Parkinson's disease susceptibility, showed suggestive associations in both models (penetrance top variant: p value = 1.1E-07; age-at-onset top variant: p value = 9.3E-07). A polygenic risk score derived from publicly available Parkinson's disease summary statistics was a significant predictor of penetrance, but not of age-at-onset.InterpretationThis study suggests that variants within or near CORO1C may modify the penetrance of LRRK2 mutations. In addition, common Parkinson's disease associated variants collectively increase the penetrance of LRRK2 mutations. ANN NEUROL 2021;90:82-94.
Published: 2021

6. Exceptionally low likelihood of Alzheimer's dementia in APOE2 homozygotes from a 5,000-person neuropathological study.

Author: Reiman, Eric M, Arboleda-Velasquez, Joseph F, Quiroz, Yakeel T, Huentelman, Matthew J, Beach, Thomas G, Caselli, Richard J, Chen, Yinghua, Su, Yi, Myers, Amanda J, Hardy, John, Paul Vonsattel, Jean, Younkin, Steven G, Bennett, David A, De Jager, Philip L, Larson, Eric B, Crane, Paul K, Keene, C Dirk, Kamboh, M Ilyas, Kofler, Julia K, Duque, Linda, Gilbert, John R, Gwirtsman, Harry E, Buxbaum, Joseph D, Dickson, Dennis W, Frosch, Matthew P, Ghetti, Bernardino F, Lunetta, Kathryn L, Wang, Li-San, Hyman, Bradley T, Kukull, Walter A, Foroud, Tatiana, Haines, Jonathan L, Mayeux, Richard P, Pericak-Vance, Margaret A, Schneider, Julie A, Trojanowski, John Q, Farrer, Lindsay A, Schellenberg, Gerard D, Beecham, Gary W, Montine, Thomas J, Jun, Gyungah R, and Alzheimer’s Disease Genetics Consortium
Subjects: Alzheimer’s Disease Genetics Consortium, Brain, Humans, Alzheimer Disease, Genetic Predisposition to Disease, Probability, Genotype, Homozygote, Alleles, Aged, Aged, 80 and over, Middle Aged, Female, Male, Apolipoprotein E2, Apolipoprotein E3, Apolipoprotein E4, Genetic Association Studies, Neuropathology, Aging, Brain Disorders, Acquired Cognitive Impairment, Dementia, Neurodegenerative, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Genetics, Alzheimer's Disease, Prevention, Neurosciences, 2.1 Biological and endogenous factors, Neurological
Abstract: Each additional copy of the apolipoprotein E4 (APOE4) allele is associated with a higher risk of Alzheimer's dementia, while the APOE2 allele is associated with a lower risk of Alzheimer's dementia, it is not yet known whether APOE2 homozygotes have a particularly low risk. We generated Alzheimer's dementia odds ratios and other findings in more than 5,000 clinically characterized and neuropathologically characterized Alzheimer's dementia cases and controls. APOE2/2 was associated with a low Alzheimer's dementia odds ratios compared to APOE2/3 and 3/3, and an exceptionally low odds ratio compared to APOE4/4, and the impact of APOE2 and APOE4 gene dose was significantly greater in the neuropathologically confirmed group than in more than 24,000 neuropathologically unconfirmed cases and controls. Finding and targeting the factors by which APOE and its variants influence Alzheimer's disease could have a major impact on the understanding, treatment and prevention of the disease.
Published: 2020

7. Author Correction: Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing

Author: Kunkle, Brian W, Grenier-Boley, Benjamin, Sims, Rebecca, Bis, Joshua C, Damotte, Vincent, Naj, Adam C, Boland, Anne, Vronskaya, Maria, van der Lee, Sven J, Amlie-Wolf, Alexandre, Bellenguez, Céline, Frizatti, Aura, Chouraki, Vincent, Martin, Eden R, Sleegers, Kristel, Badarinarayan, Nandini, Jakobsdottir, Johanna, Hamilton-Nelson, Kara L, Moreno-Grau, Sonia, Olaso, Robert, Raybould, Rachel, Chen, Yuning, Kuzma, Amanda B, Hiltunen, Mikko, Morgan, Taniesha, Ahmad, Shahzad, Vardarajan, Badri N, Epelbaum, Jacques, Hoffmann, Per, Boada, Merce, Beecham, Gary W, Garnier, Jean-Guillaume, Harold, Denise, Fitzpatrick, Annette L, Valladares, Otto, Moutet, Marie-Laure, Gerrish, Amy, Smith, Albert V, Qu, Liming, Bacq, Delphine, Denning, Nicola, Jian, Xueqiu, Zhao, Yi, Del Zompo, Maria, Fox, Nick C, Choi, Seung-Hoan, Mateo, Ignacio, Hughes, Joseph T, Adams, Hieab H, Malamon, John, Sanchez-Garcia, Florentino, Patel, Yogen, Brody, Jennifer A, Dombroski, Beth A, Naranjo, Maria Candida Deniz, Daniilidou, Makrina, Eiriksdottir, Gudny, Mukherjee, Shubhabrata, Wallon, David, Uphill, James, Aspelund, Thor, Cantwell, Laura B, Garzia, Fabienne, Galimberti, Daniela, Hofer, Edith, Butkiewicz, Mariusz, Fin, Bertrand, Scarpini, Elio, Sarnowski, Chloe, Bush, Will S, Meslage, Stéphane, Kornhuber, Johannes, White, Charles C, Song, Yuenjoo, Barber, Robert C, Engelborghs, Sebastiaan, Sordon, Sabrina, Voijnovic, Dina, Adams, Perrie M, Vandenberghe, Rik, Mayhaus, Manuel, Cupples, L Adrienne, Albert, Marilyn S, De Deyn, Peter P, Gu, Wei, Himali, Jayanadra J, Beekly, Duane, Squassina, Alessio, Hartmann, Annette M, Orellana, Adelina, Blacker, Deborah, Rodriguez-Rodriguez, Eloy, Lovestone, Simon, Garcia, Melissa E, Doody, Rachelle S, Munoz-Fernadez, Carmen, Sussams, Rebecca, Lin, Honghuang, Fairchild, Thomas J, and Benito, Yolanda A
Subjects: Biochemistry and Cell Biology, Biological Sciences, Alzheimer Disease Genetics Consortium, European Alzheimer’s Disease Initiative, Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium, Genetic and Environmental Risk in AD/Defining Genetic, Polygenic and Environmental Risk for Alzheimer’s Disease Consortium, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology, Genetics
Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Published: 2019

8. Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing

Author: Kunkle, Brian W, Grenier-Boley, Benjamin, Sims, Rebecca, Bis, Joshua C, Damotte, Vincent, Naj, Adam C, Boland, Anne, Vronskaya, Maria, van der Lee, Sven J, Amlie-Wolf, Alexandre, Bellenguez, Céline, Frizatti, Aura, Chouraki, Vincent, Martin, Eden R, Sleegers, Kristel, Badarinarayan, Nandini, Jakobsdottir, Johanna, Hamilton-Nelson, Kara L, Moreno-Grau, Sonia, Olaso, Robert, Raybould, Rachel, Chen, Yuning, Kuzma, Amanda B, Hiltunen, Mikko, Morgan, Taniesha, Ahmad, Shahzad, Vardarajan, Badri N, Epelbaum, Jacques, Hoffmann, Per, Boada, Merce, Beecham, Gary W, Garnier, Jean-Guillaume, Harold, Denise, Fitzpatrick, Annette L, Valladares, Otto, Moutet, Marie-Laure, Gerrish, Amy, Smith, Albert V, Qu, Liming, Bacq, Delphine, Denning, Nicola, Jian, Xueqiu, Zhao, Yi, Del Zompo, Maria, Fox, Nick C, Choi, Seung-Hoan, Mateo, Ignacio, Hughes, Joseph T, Adams, Hieab H, Malamon, John, Sanchez-Garcia, Florentino, Patel, Yogen, Brody, Jennifer A, Dombroski, Beth A, Naranjo, Maria Candida Deniz, Daniilidou, Makrina, Eiriksdottir, Gudny, Mukherjee, Shubhabrata, Wallon, David, Uphill, James, Aspelund, Thor, Cantwell, Laura B, Garzia, Fabienne, Galimberti, Daniela, Hofer, Edith, Butkiewicz, Mariusz, Fin, Bertrand, Scarpini, Elio, Sarnowski, Chloe, Bush, Will S, Meslage, Stéphane, Kornhuber, Johannes, White, Charles C, Song, Yuenjoo, Barber, Robert C, Engelborghs, Sebastiaan, Sordon, Sabrina, Voijnovic, Dina, Adams, Perrie M, Vandenberghe, Rik, Mayhaus, Manuel, Cupples, L Adrienne, Albert, Marilyn S, De Deyn, Peter P, Gu, Wei, Himali, Jayanadra J, Beekly, Duane, Squassina, Alessio, Hartmann, Annette M, Orellana, Adelina, Blacker, Deborah, Rodriguez-Rodriguez, Eloy, Lovestone, Simon, Garcia, Melissa E, Doody, Rachelle S, Munoz-Fernadez, Carmen, Sussams, Rebecca, Lin, Honghuang, Fairchild, Thomas J, and Benito, Yolanda A
Subjects: Biochemistry and Cell Biology, Genetics, Biological Sciences, Neurodegenerative, Dementia, Alzheimer's Disease, Aging, Prevention, Brain Disorders, Neurosciences, Clinical Research, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Human Genome, Acquired Cognitive Impairment, 2.1 Biological and endogenous factors, Aetiology, Inflammatory and immune system, Neurological, Aged, Alzheimer Disease, Amyloid beta-Peptides, Case-Control Studies, Female, Genetic Loci, Genetic Predisposition to Disease, Genetic Testing, Genome-Wide Association Study, Haplotypes, Humans, Immunity, Lipid Metabolism, Lipids, Male, tau Proteins, Alzheimer Disease Genetics Consortium (ADGC), European Alzheimer’s Disease Initiative (EADI), Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (CHARGE), Genetic and Environmental Risk in AD/Defining Genetic, Polygenic and Environmental Risk for Alzheimer’s Disease Consortium (GERAD/PERADES), Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract: Risk for late-onset Alzheimer's disease (LOAD), the most prevalent dementia, is partially driven by genetics. To identify LOAD risk loci, we performed a large genome-wide association meta-analysis of clinically diagnosed LOAD (94,437 individuals). We confirm 20 previous LOAD risk loci and identify five new genome-wide loci (IQCK, ACE, ADAM10, ADAMTS1, and WWOX), two of which (ADAM10, ACE) were identified in a recent genome-wide association (GWAS)-by-familial-proxy of Alzheimer's or dementia. Fine-mapping of the human leukocyte antigen (HLA) region confirms the neurological and immune-mediated disease haplotype HLA-DR15 as a risk factor for LOAD. Pathway analysis implicates immunity, lipid metabolism, tau binding proteins, and amyloid precursor protein (APP) metabolism, showing that genetic variants affecting APP and Aβ processing are associated not only with early-onset autosomal dominant Alzheimer's disease but also with LOAD. Analyses of risk genes and pathways show enrichment for rare variants (P = 1.32 × 10-7), indicating that additional rare variants remain to be identified. We also identify important genetic correlations between LOAD and traits such as family history of dementia and education.
Published: 2019

9. Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting

Author: Chauhan, Ganesh, Adams, Hieab HH, Satizabal, Claudia L, Bis, Joshua C, Teumer, Alexander, Sargurupremraj, Muralidharan, Hofer, Edith, Trompet, Stella, Hilal, Saima, Smith, Albert Vernon, Jian, Xueqiu, Malik, Rainer, Traylor, Matthew, Pulit, Sara L, Amouyel, Philippe, Mazoyer, Bernard, Zhu, Yi-Cheng, Kaffashian, Sara, Schilling, Sabrina, Beecham, Gary W, Montine, Thomas J, Schellenberg, Gerard D, Kjartansson, Olafur, Guðnason, Vilmundur, Knopman, David S, Griswold, Michael E, Windham, B Gwen, Gottesman, Rebecca F, Mosley, Thomas H, Schmidt, Reinhold, Saba, Yasaman, Schmidt, Helena, Takeuchi, Fumihiko, Yamaguchi, Shuhei, Nabika, Toru, Kato, Norihiro, Rajan, Kumar B, Aggarwal, Neelum T, De Jager, Philip L, Evans, Denis A, Psaty, Bruce M, Rotter, Jerome I, Rice, Kenneth, Lopez, Oscar L, Liao, Jiemin, Chen, Christopher, Cheng, Ching-Yu, Wong, Tien Y, Ikram, Mohammad K, van der Lee, Sven J, Amin, Najaf, Chouraki, Vincent, DeStefano, Anita L, Aparicio, Hugo J, Romero, Jose R, Maillard, Pauline, DeCarli, Charles, Wardlaw, Joanna M, del C. Valdés Hernández, Maria, Luciano, Michelle, Liewald, David, Deary, Ian J, Starr, John M, Bastin, Mark E, Maniega, Susana Muñoz, Slagboom, P Eline, Beekman, Marian, Deelen, Joris, Uh, Hae-Won, Lemmens, Robin, Brodaty, Henry, Wright, Margaret J, Ames, David, Boncoraglio, Giorgio B, Hopewell, Jemma C, Beecham, Ashley H, Blanton, Susan H, Wright, Clinton B, Sacco, Ralph L, Wen, Wei, Thalamuthu, Anbupalam, Armstrong, Nicola J, Chong, Elizabeth, Schofield, Peter R, Kwok, John B, van der Grond, Jeroen, Stott, David J, Ford, Ian, Jukema, J Wouter, Vernooij, Meike W, Hofman, Albert, Uitterlinden, André G, van der Lugt, Aad, Wittfeld, Katharina, Grabe, Hans J, Hosten, Norbert, von Sarnowski, Bettina, Völker, Uwe, Levi, Christopher, and Jimenez-Conde, Jordi
Subjects: Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Prevention, Genetics, Stroke, Aging, Cardiovascular, Human Genome, Brain Disorders, Cerebrovascular, 2.1 Biological and endogenous factors, Good Health and Well Being, Stroke Genetics Network (SiGN), the International Stroke Genetics Consortium (ISGC), METASTROKE, Alzheimer's Disease Genetics Consortium (ADGC), and the Neurology Working Group of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences
Abstract: ObjectiveTo explore genetic and lifestyle risk factors of MRI-defined brain infarcts (BI) in large population-based cohorts.MethodsWe performed meta-analyses of genome-wide association studies (GWAS) and examined associations of vascular risk factors and their genetic risk scores (GRS) with MRI-defined BI and a subset of BI, namely, small subcortical BI (SSBI), in 18 population-based cohorts (n = 20,949) from 5 ethnicities (3,726 with BI, 2,021 with SSBI). Top loci were followed up in 7 population-based cohorts (n = 6,862; 1,483 with BI, 630 with SBBI), and we tested associations with related phenotypes including ischemic stroke and pathologically defined BI.ResultsThe mean prevalence was 17.7% for BI and 10.5% for SSBI, steeply rising after age 65. Two loci showed genome-wide significant association with BI: FBN2, p = 1.77 × 10-8; and LINC00539/ZDHHC20, p = 5.82 × 10-9. Both have been associated with blood pressure (BP)-related phenotypes, but did not replicate in the smaller follow-up sample or show associations with related phenotypes. Age- and sex-adjusted associations with BI and SSBI were observed for BP traits (p value for BI, p [BI] = 9.38 × 10-25; p [SSBI] = 5.23 × 10-14 for hypertension), smoking (p [BI] = 4.4 × 10-10; p [SSBI] = 1.2 × 10-4), diabetes (p [BI] = 1.7 × 10-8; p [SSBI] = 2.8 × 10-3), previous cardiovascular disease (p [BI] = 1.0 × 10-18; p [SSBI] = 2.3 × 10-7), stroke (p [BI] = 3.9 × 10-69; p [SSBI] = 3.2 × 10-24), and MRI-defined white matter hyperintensity burden (p [BI] = 1.43 × 10-157; p [SSBI] = 3.16 × 10-106), but not with body mass index or cholesterol. GRS of BP traits were associated with BI and SSBI (p ≤ 0.0022), without indication of directional pleiotropy.ConclusionIn this multiethnic GWAS meta-analysis, including over 20,000 population-based participants, we identified genetic risk loci for BI requiring validation once additional large datasets become available. High BP, including genetically determined, was the most significant modifiable, causal risk factor for BI.
Published: 2019

10. Genome-Wide Linkage Study Meta-Analysis of Male Sexual Orientation

Author: Sanders, Alan R., Beecham, Gary W., Guo, Shengru, Badner, Judith A., Bocklandt, Sven, Mustanski, Brian S., Hamer, Dean H., and Martin, Eden R.
Published: 2021
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11. Genome-Wide Linkage and Association Study of Childhood Gender Nonconformity in Males

Author: Sanders, Alan R., Beecham, Gary W., Guo, Shengru, Dawood, Khytam, Rieger, Gerulf, Krishnappa, Ritesha S., Kolundzija, Alana B., Bailey, J. Michael, and Martin, Eden R.
Published: 2021
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12. Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease.

Author: Sims, Rebecca, van der Lee, Sven J, Naj, Adam C, Bellenguez, Céline, Badarinarayan, Nandini, Jakobsdottir, Johanna, Kunkle, Brian W, Boland, Anne, Raybould, Rachel, Bis, Joshua C, Martin, Eden R, Grenier-Boley, Benjamin, Heilmann-Heimbach, Stefanie, Chouraki, Vincent, Kuzma, Amanda B, Sleegers, Kristel, Vronskaya, Maria, Ruiz, Agustin, Graham, Robert R, Olaso, Robert, Hoffmann, Per, Grove, Megan L, Vardarajan, Badri N, Hiltunen, Mikko, Nöthen, Markus M, White, Charles C, Hamilton-Nelson, Kara L, Epelbaum, Jacques, Maier, Wolfgang, Choi, Seung-Hoan, Beecham, Gary W, Dulary, Cécile, Herms, Stefan, Smith, Albert V, Funk, Cory C, Derbois, Céline, Forstner, Andreas J, Ahmad, Shahzad, Li, Hongdong, Bacq, Delphine, Harold, Denise, Satizabal, Claudia L, Valladares, Otto, Squassina, Alessio, Thomas, Rhodri, Brody, Jennifer A, Qu, Liming, Sánchez-Juan, Pascual, Morgan, Taniesha, Wolters, Frank J, Zhao, Yi, Garcia, Florentino Sanchez, Denning, Nicola, Fornage, Myriam, Malamon, John, Naranjo, Maria Candida Deniz, Majounie, Elisa, Mosley, Thomas H, Dombroski, Beth, Wallon, David, Lupton, Michelle K, Dupuis, Josée, Whitehead, Patrice, Fratiglioni, Laura, Medway, Christopher, Jian, Xueqiu, Mukherjee, Shubhabrata, Keller, Lina, Brown, Kristelle, Lin, Honghuang, Cantwell, Laura B, Panza, Francesco, McGuinness, Bernadette, Moreno-Grau, Sonia, Burgess, Jeremy D, Solfrizzi, Vincenzo, Proitsi, Petra, Adams, Hieab H, Allen, Mariet, Seripa, Davide, Pastor, Pau, Cupples, L Adrienne, Price, Nathan D, Hannequin, Didier, Frank-García, Ana, Levy, Daniel, Chakrabarty, Paramita, Caffarra, Paolo, Giegling, Ina, Beiser, Alexa S, Giedraitis, Vilmantas, Hampel, Harald, Garcia, Melissa E, Wang, Xue, Lannfelt, Lars, Mecocci, Patrizia, Eiriksdottir, Gudny, Crane, Paul K, Pasquier, Florence, and Boccardi, Virginia
Subjects: ARUK Consortium, GERAD/PERADES, CHARGE, ADGC, EADI, Microglia, Humans, Alzheimer Disease, Genetic Predisposition to Disease, Adaptor Proteins, Signal Transducing, Membrane Glycoproteins, Receptors, Immunologic, Odds Ratio, Case-Control Studies, Gene Expression Profiling, Amino Acid Sequence, Sequence Homology, Amino Acid, Gene Frequency, Genotype, Linkage Disequilibrium, Polymorphism, Single Nucleotide, Phospholipase C gamma, Immunity, Innate, Protein Interaction Maps, Exome, Neurodegenerative, Brain Disorders, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Dementia, Alzheimer's Disease, Aging, Acquired Cognitive Impairment, 2.1 Biological and endogenous factors, Developmental Biology, Biological Sciences, Medical and Health Sciences
Abstract: We identified rare coding variants associated with Alzheimer's disease in a three-stage case-control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10-8) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10-10, odds ratio (OR) = 0.68, minor allele frequency (MAF)cases = 0.0059, MAFcontrols = 0.0093), a risk variant in ABI3 (rs616338: p.Ser209Phe, P = 4.56 × 10-10, OR = 1.43, MAFcases = 0.011, MAFcontrols = 0.008), and a new genome-wide significant variant in TREM2 (rs143332484: p.Arg62His, P = 1.55 × 10-14, OR = 1.67, MAFcases = 0.0143, MAFcontrols = 0.0089), a known susceptibility gene for Alzheimer's disease. These protein-altering changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified risk genes in Alzheimer's disease. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's disease.
Published: 2017

13. Transethnic genome‐wide scan identifies novel Alzheimer's disease loci

Author: Jun, Gyungah R, Chung, Jaeyoon, Mez, Jesse, Barber, Robert, Beecham, Gary W, Bennett, David A, Buxbaum, Joseph D, Byrd, Goldie S, Carrasquillo, Minerva M, Crane, Paul K, Cruchaga, Carlos, De Jager, Philip, Ertekin‐Taner, Nilufer, Evans, Denis, Fallin, M Danielle, Foroud, Tatiana M, Friedland, Robert P, Goate, Alison M, Graff‐Radford, Neill R, Hendrie, Hugh, Hall, Kathleen S, Hamilton‐Nelson, Kara L, Inzelberg, Rivka, Kamboh, M Ilyas, Kauwe, John SK, Kukull, Walter A, Kunkle, Brian W, Kuwano, Ryozo, Larson, Eric B, Logue, Mark W, Manly, Jennifer J, Martin, Eden R, Montine, Thomas J, Mukherjee, Shubhabrata, Naj, Adam, Reiman, Eric M, Reitz, Christiane, Sherva, Richard, St. George‐Hyslop, Peter H, Thornton, Timothy, Younkin, Steven G, Vardarajan, Badri N, 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 S, Barmada, Michjael M, Barnes, Lisa L, Beach, Thomas G, Becker, James T, Bigio, Eileen H, Bird, Thomas D, Blacker, Deborah, Boeve, Bradley F, Bowen, James D, Boxer, Adam, Burke, James R, Cairns, Nigel J, Cao, Chuanhai, Carlson, Chris S, Carlsson, Cynthia M, Carney, Regina M, Carroll, Steven L, Chui, Helena C, Clark, David G, Corneveaux, Jason, Cribbs, David H, Crocco, Elizabeth A, De Jager, Philip L, DeCarli, Charles, DeKosky, Steven T, Demirci, F Yesim, Dick, Malcolm, Dickson, Dennis W, Doody, Rachelle S, Duara, Ranjan, Faber, Kelley M, Fairchild, Thomas J, Fallon, Kenneth B, Farlow, Martin R, Ferris, Steven, Frosch, Matthew P, Galasko, Douglas R, Gearing, Marla, Geschwind, Daniel H, Ghetti, Bernardino, Gilbert, John R, Glass, Jonathan D, Green, Robert C, and Growdon, John H
Subjects: Biomedical and Clinical Sciences, Biological Psychology, Clinical Sciences, Neurosciences, Psychology, Neurodegenerative, Brain Disorders, Human Genome, Genetics, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Alzheimer's Disease, Prevention, Biotechnology, Aging, Dementia, Acquired Cognitive Impairment, 2.1 Biological and endogenous factors, Adaptor Proteins, Signal Transducing, Alzheimer Disease, Apolipoprotein E4, GTPase-Activating Proteins, Genetic Predisposition to Disease, Genome-Wide Association Study, Heparin-binding EGF-like Growth Factor, Humans, Membrane Glycoproteins, Molecular Chaperones, NFI Transcription Factors, Peroxisomal Bifunctional Enzyme, Polymorphism, Single Nucleotide, Receptors, GABA, Alzheimer's Disease Genetics Consortium, APOE interaction, Alzheimer's disease, Genome-wide association, Transethnic, Geriatrics, Clinical sciences, Biological psychology
Abstract: IntroductionGenetic 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.MethodsWe 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.ResultsGenome-wide significant (GWS) associations in single-nucleotide polymorphism (SNP)-based tests (P
Published: 2017

14. Genomic evidence consistent with antagonistic pleiotropy may help explain the evolutionary maintenance of same-sex sexual behaviour in humans

Author: Zietsch, Brendan P., Sidari, Morgan J., Abdellaoui, Abdel, Maier, Robert, Långström, Niklas, Guo, Shengru, Beecham, Gary W., Martin, Eden R., Sanders, Alan R., and Verweij, Karin J. H.
Published: 2021
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15. Disentangling the genetic underpinnings of neuropsychiatric symptoms in Alzheimer's disease in the Alzheimer's Disease Sequencing Project: Study design and methodology.

Author: Ray, Nicholas R., Kumar, Ajneesh, Zaman, Andrew, del Rosario, Pamela, Mena, Pedro R., Manoochehri, Masood, Stein, Colin, De Vito, Alyssa N., Sweet, Robert A., Hohman, Timothy J., Cuccaro, Michael L., Beecham, Gary W., Huey, Edward D., and Reitz, Christiane
Subjects: ALZHEIMER'S disease, DATA warehousing, MENTAL illness, SEQUENCE analysis, GENETICS, APOLIPOPROTEIN E4
Abstract: INTRODUCTION: Neuropsychiatric symptoms (NPS) are highly prevalent in Alzheimer's disease (AD). There are no effective treatments targeting these symptoms. METHODS: To facilitate identification of causative mechanistic pathways, we initiated an effort (NIH: U01AG079850) to collate, harmonize, and analyze all available NPS data (≈ 100,000 samples) of diverse ancestries with whole‐genome sequencing data from the Alzheimer's Disease Sequencing Project (ADSP). RESULTS: This study will generate a genomic resource for Alzheimer's disease with both harmonized whole‐genome sequencing and NPS phenotype data that will be publicly available through NIAGADS. Primary analyses will (1) identify novel genetic risk factors associated with NPS in AD, (2) characterize the shared genetic architecture of NPS in AD and primary psychiatric disorders, and (3) assess the role of ancestry effects in the etiology of NPS in AD. DISCUSSION: Expansion of the ADSP to harmonize and refine NPS phenotypes coupled with the proposed core analyses will lay the foundation to disentangle the molecular mechanisms underlying these detrimental symptoms in AD in diverse populations. Highlights: Neuropsychiatric symptoms (NPS) are highly prevalent in Alzheimer's disease (AD).There are no effective treatments targeting NPS in AD.The current effort aims to collate, harmonize, and analyze all NPS data from the Alzheimer's Disease Sequencing Project.Core analyses will identify underlying genetic factors and mechanistic pathways.The harmonized genomic and phenotypic data from this initiative will be available through National Institute on Aging Genetics of Alzheimer's Disease Data Storage Site. [ABSTRACT FROM AUTHOR]
Published: 2024
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16. African Ancestry Individuals with Higher Educational Attainment Are Resilient to Alzheimer’s Disease Measured by pTau181

Author: Rajabli, Farid, primary, Seixas, Azizi A., additional, Akgun, Bilcag, additional, Adams, Larry D., additional, Inciute, Jovita, additional, Hamilton, Kara L., additional, Whithead, Patrice G., additional, Konidari, Ioanna, additional, Gu, Tianjie, additional, Arvizu, Jamie, additional, Golightly, Charles G., additional, Starks, Takiyah D., additional, Laux, Renee, additional, Byrd, Goldie S., additional, Haines, Jonathan L., additional, Beecham, Gary W., additional, Griswold, Anthony J., additional, Vance, Jeffery M., additional, Cuccaro, Michael L., additional, and Pericak-Vance, Margaret A., additional
Published: 2024
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17. ABCA7 frameshift deletion associated with Alzheimer disease in African Americans

Author: Cukier, Holly N, Kunkle, Brian W, Vardarajan, Badri N, Rolati, Sophie, Hamilton-Nelson, Kara L, Kohli, Martin A, Whitehead, Patrice L, Dombroski, Beth A, Van Booven, Derek, Lang, Rosalyn, Dykxhoorn, Derek M, Farrer, Lindsay A, Cuccaro, Michael L, Vance, Jeffery M, Gilbert, John R, Beecham, Gary W, Martin, Eden R, Carney, Regina M, Mayeux, Richard, Schellenberg, Gerard D, Byrd, Goldie S, Haines, Jonathan L, Pericak-Vance, Margaret A, Albert, Marilyn S, Albin, Roger L, Apostolova, Liana G, Arnold, Steven E, Asthana, Sanjay, Atwood, Craig S, Baldwin, Clinton T, Barmada, M Michael, Barnes, Lisa L, Barral, Sandra, Beach, Thomas G, Becker, James T, Beekly, Duane, Bennett, David A, Bigio, Eileen H, Bird, Thomas D, Blacker, Deborah, Boeve, Bradley F, Boxer, Adam, Burke, James R, Burns, Jeffrey M, Buxbaum, Joseph D, Cai, Guiqing, Cairns, Nigel J, Cantwell, Laura B, Cao, Chuanhai, Carlsson, Cynthia M, Carrasquillo, Minerva M, Carroll, Steven L, Chui, Helena C, Clark, David G, Cribbs, David H, Crocco, Elizabeth A, Cruchaga, Carlos, De Jager, Philip L, DeCarli, Charles, Demirci, F Yesim, Dick, Malcolm, Dickson, Dennis W, Duara, Ranjan, Ertekin-Taner, Nilufer, Evans, Denis A, Faber, Kelley M, Fallin, M Daniele, Fallon, Kenneth B, Fardo, David W, Farlow, Martin R, Ferris, Steven, Foroud, Tatiana M, Frosch, Matthew P, Galasko, Douglas R, Gearing, Marla, Geschwind, Daniel H, Ghetti, Bernardino, Go, Rodney CP, Goate, Alison M, Graff-Radford, Neill R, Green, Robert C, Griffith, Patrick, Growdon, John H, Hakonarson, Hakon, Hamilton, Ronald L, Haroutunian, Vahram, Harrell, Lindy E, Honig, Lawrence S, Huebinger, Ryan M, Hulette, Christine M, Hyman, Bradley T, Jicha, Gregory A, and Jin, Lee-Way
Subjects: Biological Sciences, Genetics, Human Genome, Neurodegenerative, Neurosciences, Dementia, Aging, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Acquired Cognitive Impairment, Alzheimer's Disease, Clinical Research, Brain Disorders, 2.1 Biological and endogenous factors, Aetiology, Alzheimer's Disease Genetics Consortium, Clinical sciences
Abstract: ObjectiveTo identify a causative variant(s) that may contribute to Alzheimer disease (AD) in African Americans (AA) in the ATP-binding cassette, subfamily A (ABC1), member 7 (ABCA7) gene, a known risk factor for late-onset AD.MethodsCustom capture sequencing was performed on ∼150 kb encompassing ABCA7 in 40 AA cases and 37 AA controls carrying the AA risk allele (rs115550680). Association testing was performed for an ABCA7 deletion identified in large AA data sets (discovery n = 1,068; replication n = 1,749) and whole exome sequencing of Caribbean Hispanic (CH) AD families.ResultsA 44-base pair deletion (rs142076058) was identified in all 77 risk genotype carriers, which shows that the deletion is in high linkage disequilibrium with the risk allele. The deletion was assessed in a large data set (531 cases and 527 controls) and, after adjustments for age, sex, and APOE status, was significantly associated with disease (p = 0.0002, odds ratio [OR] = 2.13 [95% confidence interval (CI): 1.42-3.20]). An independent data set replicated the association (447 cases and 880 controls, p = 0.0117, OR = 1.65 [95% CI: 1.12-2.44]), and joint analysis increased the significance (p = 1.414 × 10(-5), OR = 1.81 [95% CI: 1.38-2.37]). The deletion is common in AA cases (15.2%) and AA controls (9.74%), but in only 0.12% of our non-Hispanic white cohort. Whole exome sequencing of multiplex, CH families identified the deletion cosegregating with disease in a large sibship. The deleted allele produces a stable, detectable RNA strand and is predicted to result in a frameshift mutation (p.Arg578Alafs) that could interfere with protein function.ConclusionsThis common ABCA7 deletion could represent an ethnic-specific pathogenic alteration in AD.
Published: 2016

18. Assessment of the genetic variance of late-onset Alzheimer's disease

Author: Ridge, Perry G, Hoyt, Kaitlyn B, Boehme, Kevin, Mukherjee, Shubhabrata, Crane, Paul K, Haines, Jonathan L, Mayeux, Richard, Farrer, Lindsay A, Pericak-Vance, Margaret A, Schellenberg, Gerard D, Kauwe, John SK, Consortium, Alzheimer's Disease Genetics, Adams, Perrie M, Albert, Marilyn S, Albin, Roger L, Apostolova, Liana G, Arnold, Steven E, Asthana, Sanjay, Atwood, Craig S, Baldwin, Clinton T, Barber, Robert C, Barmada, Michael M, Barnes, Lisa L, Barral, Sandra, Beach, Thomas G, Becker, James T, Beecham, Gary W, Beekly, Duane, Bennett, David A, Bigio, Eileen H, Bird, Thomas D, Blacker, Deborah, Boeve, Bradley F, Bowen, James D, Boxer, Adam, Burke, James R, Burns, Jeffrey M, Buxbaum, Joseph D, Cairns, Nigel J, Cantwell, Laura B, Cao, Chuanhai, Carlson, Chris S, Carlsson, Cynthia M, Carney, Regina M, Carrasquillo, Minerva M, Carroll, Steven L, Chui, Helena C, Clark, David G, Corneveaux, Jason, Cribbs, David H, Crocco, Elizabeth A, Cruchaga, Carlos, De Jager, Philip L, DeCarli, Charles, Demirci, F Yesim, Dick, Malcolm, Dickson, Dennis W, Doody, Rachelle S, Duara, Ranjan, Ertekin-Taner, Nilufer, Evans, Denis A, Faber, Kelley M, Fairchild, Thomas J, Fallon, Kenneth B, Fardo, David W, Farlow, Martin R, Ferris, Steven, Foroud, Tatiana M, Frosch, Matthew P, Galasko, Douglas R, Gearing, Marla, Geschwind, Daniel H, Ghetti, Bernardino, Gilbert, John R, Goate, Alison M, Graff-Radford, Neill R, Green, Robert C, Growdon, John H, Hakonarson, Hakon, Hamilton, Ronald L, Hamilton-Nelson, Kara L, Hardy, John, Harrell, Lindy E, Honig, Lawrence S, Huebinger, Ryan M, Huentelman, Matthew J, Hulette, Christine M, Hyman, Bradley T, Jarvik, Gail P, Jicha, Gregory A, Jin, Lee-Way, Jun, Gyungah, Kamboh, M Ilyas, Karydas, Anna, Katz, Mindy J, Kaye, Jeffrey A, Kim, Ronald, and Kowall, Neil W
Subjects: Biological Psychology, Biomedical and Clinical Sciences, Neurosciences, Psychology, Human Genome, Genetics, Brain Disorders, Aging, Alzheimer's Disease, Neurodegenerative, Dementia, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Acquired Cognitive Impairment, 2.1 Biological and endogenous factors, Neurological, Aged, Aged, 80 and over, Alzheimer Disease, Amyloid beta-Protein Precursor, Datasets as Topic, Female, Genetic Variation, Genome-Wide Association Study, Humans, Male, Membrane Glycoproteins, Netrin Receptors, Polymorphism, Single Nucleotide, Receptors, Cell Surface, Receptors, Immunologic, Risk, Alzheimer's Disease Genetics Consortium, Alzheimer's disease, Genetic variance, Clinical Sciences, Neurology & Neurosurgery, Biological psychology
Abstract: Alzheimer's disease (AD) is a complex genetic disorder with no effective treatments. More than 20 common markers have been identified, which are associated with AD. Recently, several rare variants have been identified in Amyloid Precursor Protein (APP), Triggering Receptor Expressed On Myeloid Cells 2 (TREM2) and Unc-5 Netrin Receptor C (UNC5C) that affect risk for AD. Despite the many successes, the genetic architecture of AD remains unsolved. We used Genome-wide Complex Trait Analysis to (1) estimate phenotypic variance explained by genetics; (2) calculate genetic variance explained by known AD single nucleotide polymorphisms (SNPs); and (3) identify the genomic locations of variation that explain the remaining unexplained genetic variance. In total, 53.24% of phenotypic variance is explained by genetics, but known AD SNPs only explain 30.62% of the genetic variance. Of the unexplained genetic variance, approximately 41% is explained by unknown SNPs in regions adjacent to known AD SNPs, and the remaining unexplained genetic variance outside these regions.
Published: 2016

19. PARK10 is a major locus for sporadic neuropathologically confirmed Parkinson disease

Author: Beecham, Gary W, Dickson, Dennis W, Scott, William K, Martin, Eden R, Schellenberg, Gerard, Nuytemans, Karen, Larson, Eric B, Buxbaum, Joseph D, Trojanowski, John Q, Van Deerlin, Vivianna M, Hurtig, Howard I, Mash, Deborah C, Beach, Thomas G, Troncoso, Juan C, Pletnikova, Olga, Frosch, Matthew P, Ghetti, Bernardino, Foroud, Tatiana M, Honig, Lawrence S, Marder, Karen, Vonsattel, Jean Paul, Goldman, Samuel M, Vinters, Harry V, Ross, Owen A, Wszolek, Zbigniew K, Wang, Liyong, Dykxhoorn, Derek M, Pericak-Vance, Margaret A, Montine, Thomas J, Leverenz, James B, Dawson, Ted M, and Vance, Jeffery M
Subjects: Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Genetics, Brain Disorders, Aging, Neurodegenerative, Prevention, Human Genome, Parkinson's Disease, Aetiology, 2.1 Biological and endogenous factors, Neurological, Aged, Aged, 80 and over, Chromosomes, Human, Pair 1, Female, Genetic Loci, Genome-Wide Association Study, Humans, Linkage Disequilibrium, Male, Parkinson Disease, Polymorphism, Single Nucleotide, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences
Abstract: ObjectiveTo minimize pathologic heterogeneity in genetic studies of Parkinson disease (PD), the Autopsy-Confirmed Parkinson Disease Genetics Consortium conducted a genome-wide association study using both patients with neuropathologically confirmed PD and controls.MethodsFour hundred eighty-four cases and 1,145 controls met neuropathologic diagnostic criteria, were genotyped, and then imputed to 3,922,209 variants for genome-wide association study analysis.ResultsA small region on chromosome 1 was strongly associated with PD (rs10788972; p = 6.2 × 10(-8)). The association peak lies within and very close to the maximum linkage peaks of 2 prior positive linkage studies defining the PARK10 locus. We demonstrate that rs10788972 is in strong linkage disequilibrium with rs914722, the single nucleotide polymorphism defining the PARK10 haplotype previously shown to be significantly associated with age at onset in PD. The region containing the PARK10 locus was significantly reduced from 10.6 megabases to 100 kilobases and contains 4 known genes: TCEANC2, TMEM59, miR-4781, and LDLRAD1.ConclusionsWe confirm the association of a PARK10 haplotype with the risk of developing idiopathic PD. Furthermore, we significantly reduce the size of the PARK10 region. None of the candidate genes in the new PARK10 region have been previously implicated in the biology of PD, suggesting new areas of potential research. This study strongly suggests that reducing pathologic heterogeneity may enhance the application of genetic association studies to PD.
Published: 2015

20. Rarity of the Alzheimer Disease-Protective APP A673T Variant in the United States

Author: Wang, Li-San, Naj, Adam C, Graham, Robert R, Crane, Paul K, Kunkle, Brian W, Cruchaga, Carlos, Murcia, Josue D. Gonzalez, Cannon-Albright, Lisa, Baldwin, Clinton T, Zetterberg, Henrik, Blennow, Kaj, Kukull, Walter A, Faber, Kelley M, Schupf, Nicole, Norton, Maria C, Tschanz, JoAnn T, Munger, Ronald G, Corcoran, Christopher D, Rogaeva, Ekaterina, Lin, Chiao-Feng, Dombroski, Beth A, Cantwell, Laura B, Partch, Amanda, Valladares, Otto, Hakonarson, Hakon, St George-Hyslop, Peter, Green, Robert C, Goate, Alison M, Foroud, Tatiana M, Carney, Regina M, Larson, Eric B, Behrens, Timothy W, Kauwe, John S. K, Haines, Jonathan L, Farrer, Lindsay A, Pericak-Vance, Margaret A, Mayeux, Richard, Schellenberg, Gerard D, Albert, Marilyn S, Albin, Roger L, Apostolova, Liana G, Arnold, Steven E, Barber, Robert, Barmada, M. Michael, Barnes, Lisa L, Beach, Thomas G, Becker, James T, Beecham, Gary W, Beekly, Duane, Bennett, David A, Bigio, Eileen H, Bird, Thomas D, Blacker, Deborah, Boeve, Bradley F, Bowen, James D, Boxer, Adam, Burke, James R, Buxbaum, Joseph D, Cairns, Nigel J, Cao, Chuanhai, Carlson, Chris S, Carroll, Steven L, Chui, Helena C, Clark, David G, Cribbs, David H, Crocco, Elizabeth A, DeCarli, Charles, DeKosky, Steven T, Demirci, F. Yesim, Dick, Malcolm, Dickson, Dennis W, Duara, Ranjan, Ertekin-Taner, Nilufer, Fallon, Kenneth B, Farlow, Martin R, Ferris, Steven, Frosch, Matthew P, Galasko, Douglas R, Ganguli, Mary, Gearing, Marla, Geschwind, Daniel H, Ghetti, Bernardino, Gilbert, John R, Glass, Jonathan D, Graff-Radford, Neill R, Growdon, John H, Hamilton, Ronald L, Hamilton-Nelson, Kara L, Harrell, Lindy E, Head, Elizabeth, Honig, Lawrence S, Hulette, Christine M, Hyman, Bradley T, Jarvik, Gail P, Jicha, Gregory A, Jin, Lee-Way, Jun, Gyungah, Kamboh, M. Ilyas, Karydas, Anna, and Kaye, Jeffrey A
Published: 2015

21. Effects of Multiple Genetic Loci on Age at Onset in Late-Onset Alzheimer Disease

Author: Naj, Adam C, Jun, Gyungah, Reitz, Christiane, Kunkle, Brian W, Perry, William, Park, Yo Son, Beecham, Gary W, Rajbhandary, Ruchita A, Hamilton-Nelson, Kara L, Wang, Li-San, Kauwe, John S. K, Huentelman, Matthew J, Myers, Amanda J, Bird, Thomas D, Boeve, Bradley F, Baldwin, Clinton T, Jarvik, Gail P, Crane, Paul K, Rogaeva, Ekaterina, Barmada, M. Michael, Demirci, F. Yesim, Cruchaga, Carlos, Kramer, Patricia L, Ertekin-Taner, Nilufer, Hardy, John, Graff-Radford, Neill R, Green, Robert C, Larson, Eric B, St. George-Hyslop, Peter H, Buxbaum, Joseph D, Evans, Denis A, Schneider, Julie A, Lunetta, Kathryn L, Kamboh, M. Ilyas, Saykin, Andrew J, Reiman, Eric M, De Jager, Philip L, Bennett, David A, Morris, John C, Montine, Thomas J, Goate, Alison M, Blacker, Deborah, Tsuang, Debby W, Hakonarson, Hakon, Kukull, Walter A, Foroud, Tatiana M, Martin, Eden R, Haines, Jonathan L, Mayeux, Richard P, Farrer, Lindsay A, Schellenberg, Gerard D, Pericak-Vance, Margaret A, Albert, Marilyn S, Albin, Roger L, Apostolova, Liana G, Arnold, Steven E, Barber, Robert, Barnes, Lisa L, Beach, Thomas G, Becker, James T, Beekly, Duane, Bigio, Eileen H, Bowen, James D, Boxer, Adam, Burke, James R, Cairns, Nigel J, Cantwell, Laura B, Cao, Chuanhai, Carlson, Chris S, Carney, Regina M, Carrasquillo, Minerva M, Carroll, Steven L, Chui, Helena C, Clark, David G, Corneveaux, Jason, Cribbs, David H, Crocco, Elizabeth A, DeCarli, Charles, DeKosky, Steven T, Dick, Malcolm, Dickson, Dennis W, Duara, Ranjan, Faber, Kelley M, Fallon, Kenneth B, Farlow, Martin R, Ferris, Steven, Frosch, Matthew P, Galasko, Douglas R, Ganguli, Mary, Gearing, Marla, Geschwind, Daniel H, Ghetti, Bernardino, Gilbert, John R, Glass, Jonathan D, Growdon, John H, Hamilton, Ronald L, Harrell, Lindy E, Head, Elizabeth, Honig, Lawrence S, and Hulette, Christine M
Published: 2014

22. Tau and Amyloid Plasma Biomarker Analysis in Alzheimer’s Disease Cohorts from Diverse Genetic Ancestries

Author: Griswold, Anthony J., primary, Rajabli, Farid, additional, Gu, Tianjie, additional, Garcia‐Serje, Catherine, additional, Arvizu, Jamie, additional, Golightly, Charles G., additional, Whitehead, Patrice, additional, Hamilton‐Nelson, Kara L., additional, Adams, Larry D., additional, Celis, Katrina, additional, Sanchez, Jose Javier, additional, Tejada, Sergio J., additional, Mena, Pedro R., additional, Starks, Takiyah D., additional, Cornejo‐Olivas, Mario, additional, Illanes‐Manrique, Maryenela Z, additional, Silva‐Vergara, Concepcion, additional, Cuccaro, Michael L., additional, Vance, Jeffery M., additional, Feliciano‐Astacio, Briseida E., additional, Byrd, Goldie S., additional, Beecham, Gary W., additional, Haines, Jonathan L., additional, and Pericak‐Vance, Margaret A., additional
Published: 2023
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23. Impact of COVID‐19 in cognitively unimpaired individuals and dementia caregivers from the Peruvian Alzheimer Disease Initiative (PeADI)

Author: Illanes‐Manrique, Maryenela, primary, Mena, Pedro R., additional, Cubas‐Montecino, Diana, additional, Adams, Larry D., additional, Sarapura‐Castro, Elison, additional, Castro‐Suarez, Sheila, additional, Rios‐Pinto, Julia, additional, Mejía, Koni K., additional, Medina‐Colque, Angel, additional, Beecham, Gary W., additional, Cornejo‐Herrera, Ivan, additional, Vance, Jeffery M., additional, Ochoa‐Valle, Edward, additional, Cuccaro, Michael L., additional, Cornejo‐Olivas, Mario, additional, and Pericak‐Vance, Margaret A., additional
Published: 2023
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24. Assessing the functional effect of the Presenilin‐1 G206A variant on age of onset of Alzheimer Disease in the Puerto Rican population

Author: Celis, Katrina, primary, Rajabli, Farid, additional, Griswold, Anthony J., additional, Adams, Larry D., additional, Tejada, Sergio J., additional, Sanchez, Jose Javier, additional, Simon, Shaina A., additional, Hamilton‐Nelson, Kara L., additional, Gomez, Nicholas R, additional, Whitehead, Patrice, additional, Mena, Pedro R., additional, Arvizu, Jamie, additional, Golightly, Charles G., additional, Silva, Concepcion, additional, Acosta, Heriberto, additional, Cuccaro, Michael L., additional, Vance, Jeffery M., additional, Beecham, Gary W., additional, Feliciano‐Astacio, Briseida E., additional, Dykxhoorn, Derek M., additional, Young, Juan I., additional, and Pericak‐Vance, Margaret A., additional
Published: 2023
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25. Cerebral amyloid angiopathy and neuritic plaques impact tangle burden and cognitive decline in a heterogeneous clinical population

Author: Godrich, Dana, primary, Pasteris, Jeremy, additional, Martin, Eden R., additional, Schellenberg, Gerald D., additional, Pericak‐Vance, Margaret A., additional, Cuccaro, Michael L., additional, Scott, William K., additional, Rundek, Tatjana, additional, Kukull, Walter A., additional, Montine, Thomas J., additional, and Beecham, Gary W., additional
Published: 2023
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26. Recruitment and Retention in the Puerto Rico Alzheimer’s Disease Initiative

Author: Feliciano‐Astacio, Briseida E., primary, Rajabli, Farid, additional, Prough, Michael B., additional, Hamilton‐Nelson, Kara L., additional, Adams, Larry D., additional, Mena, Pedro R., additional, Tejada, Sergio J., additional, Sanchez, Jose Javier, additional, Celis, Katrina, additional, Silva‐Vergara, Concepcion, additional, Whitehead, Patrice, additional, Acosta, Heriberto, additional, Feliciano, Nereida I, additional, Chinea, Angel, additional, McInerney, Katalina, additional, Vance, Jeffery M., additional, Cuccaro, Michael L., additional, Beecham, Gary W., additional, and Pericak‐Vance, Margaret A., additional
Published: 2023
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27. Genomic editing of APOE4/4 to APOE3/3 in iPSCs bearing African or European local ancestry surrounding APOE

Author: Oron, Oded, primary, DeRosa, Brooke A., additional, Rajabli, Farid, additional, Celis, Katrina, additional, Feliciano‐Astacio, Briseida E., additional, Silva‐Vergara, Concepcion, additional, Beecham, Gary W., additional, Adams, Larry D., additional, Tejada, Sergio J., additional, Mena, Pedro R., additional, Whitehead, Patrice, additional, Hamilton‐Nelson, Kara L., additional, Starks, Takiyah D., additional, Byrd, Goldie S., additional, Cuccaro, Michael L., additional, Young, Juan I., additional, Pericak‐Vance, Margaret A., additional, Vance, Jeffery M., additional, and Dykxhoorn, Derek M., additional
Published: 2023
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28. MCI in Caribbean Hispanics shows increased impairment in attention and working memory domains relative to non‐Hispanic White individuals

Author: McInerney, Katalina, primary, Zaman, Andrew, additional, Mena, Pedro R., additional, Adams, Larry D., additional, Tejada, Sergio J., additional, Sanchez, Jose Javier, additional, Celis, Katrina, additional, Hamilton‐Nelson, Kara L., additional, Feliciano‐Astacio, Briseida E., additional, Rajabli, Farid, additional, Beecham, Gary W., additional, Vance, Jeffery M., additional, Cuccaro, Michael L., additional, and Pericak‐Vance, Margaret A., additional
Published: 2023
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29. Uncovering the Role of an ABCA7 Frameshift Deletion in African American Alzheimer’s Disease Cellular Pathology

Author: DeRosa, Brooke A., primary, Nam, Younji, additional, Golightly, Charles G., additional, Simon, Shaina A., additional, Arvizu, Jamie, additional, Adams, Larry D., additional, Starks, Takiyah D., additional, Laverde‐Paz, Juliana, additional, Cukier, Holly N., additional, Vance, Jeffery M., additional, Cuccaro, Michael L., additional, Haines, Jonathan L., additional, Byrd, Goldie S., additional, Beecham, Gary W., additional, Pericak‐Vance, Margaret A., additional, and Dykxhoorn, Derek M., additional
Published: 2023
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30. Linkage analysis of multiplex Caribbean Hispanic families loaded for unexplained early-onset cases identifies novel Alzheimer's disease loci

Author: Cheng, Rong, Tang, Min, Martinez, Izri, Ayodele, Temitope, Baez, Penelope, Reyes-Dumeyer, Dolly, Lantigua, Rafael, Medrano, Martin, Jimenez-Velazquez, Ivonne, Lee, Joseph H., Beecham, Gary W., and Reitz, Christiane
Published: 2018
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31. C9ORF72 intermediate repeat copies are a significant risk factor for Parkinson disease.

Author: Nuytemans, Karen, Bademci, Güney, Kohli, Martin M, Beecham, Gary W, Wang, Liyong, Young, Juan I, Nahab, Fatta, Martin, Eden R, Gilbert, John R, Benatar, Michael, Haines, Jonathan L, Scott, William K, Züchner, Stephan, Pericak-Vance, Margaret A, and Vance, Jeffery M
Subjects: Humans, Parkinson Disease, Genetic Predisposition to Disease, Proteins, Risk Factors, Case-Control Studies, Pedigree, Repetitive Sequences, Nucleic Acid, Genotype, Gene Dosage, Phenotype, Adolescent, Adult, Aged, Aged, 80 and over, Middle Aged, Child, Young Adult, C9ORF72 repeat, Parkinson disease, association, risk factor, C9orf72 Protein, Genetics & Heredity, Clinical Sciences
Abstract: We set out to determine whether expansions in the C9ORF72 repeat found in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) families are associated with Parkinson disease (PD). We determined the repeat size in a total of 889 clinically ascertained patients (including PD and essential tremor plus Parkinsonism (ETP)) and 1144 controls using a repeat-primed PCR assay. We found that large C9ORF72 repeat expansions (>30 repeats) were not contributing to PD risk. However, PD and ETP cases had a significant increase in intermediate (>20 to 30+) repeat copies compared to controls. Overall, 14 cases (13 PD, 1 ETP) and three controls had >20 repeat copies (Fisher's exact test p = 0.002). Further, seven cases and no controls had >23 repeat copies (p = 0.003). Our results suggest that intermediate copy numbers of the C9ORF72 repeat contribute to risk for PD and ETP. This also suggests that PD, ALS and FTD share some pathophysiological mechanisms of disease. Further studies are needed to elucidate the contribution of the C9ORF72 repeat in the overall PD population and to determine whether other common genetic risk factors exist between these neurodegenerative disorders.
Published: 2013

32. Novel late-onset Alzheimer disease loci variants associate with brain gene expression.

Author: Allen, Mariet, Zou, Fanggeng, Chai, High Seng, Younkin, Curtis S, Crook, Julia, Pankratz, V Shane, Carrasquillo, Minerva M, Rowley, Christopher N, Nair, Asha A, Middha, Sumit, Maharjan, Sooraj, Nguyen, Thuy, Ma, Li, Malphrus, Kimberly G, Palusak, Ryan, Lincoln, Sarah, Bisceglio, Gina, Georgescu, Constantin, Schultz, Debra, Rakhshan, Fariborz, Kolbert, Christopher P, Jen, Jin, Haines, Jonathan L, Mayeux, Richard, Pericak-Vance, Margaret A, Farrer, Lindsay A, Schellenberg, Gerard D, Petersen, Ronald C, Graff-Radford, Neill R, Dickson, Dennis W, Younkin, Steven G, Ertekin-Taner, Nilüfer, Alzheimer's Disease Genetics Consortium (ADGC), Apostolova, Liana G, Arnold, Steven E, Baldwin, Clinton T, Barber, Robert, Barmada, Michael M, Beach, Thomas, Beecham, Gary W, Beekly, Duane, Bennett, David A, Bigio, Eileen H, Bird, Thomas D, Blacker, Deborah, Boeve, Bradley F, Bowen, James D, Boxer, Adam, Burke, James R, Buros, Jacqueline, Buxbaum, Joseph D, Cairns, Nigel J, Cantwell, Laura B, Cao, Chuanhai, Carlson, Chris S, Carney, Regina M, Carroll, Steven L, Chui, Helena C, Clark, David G, Corneveaux, Jason, Cotman, Carl W, Crane, Paul K, Cruchaga, Carlos, Cummings, Jeffrey L, De Jager, Philip L, DeCarli, Charles, DeKosky, Steven T, Demirci, F Yesim, Diaz-Arrastia, Ramon, Dick, Malcolm, Dombroski, Beth A, Duara, Ranjan, Ellis, William D, Evans, Denis, Faber, Kelley M, Fallon, Kenneth B, Farlow, Martin R, Ferris, Steven, Foroud, Tatiana M, Frosch, Matthew, Galasko, Douglas R, Gallins, Paul J, Ganguli, Mary, Gearing, Marla, Geschwind, Daniel H, Ghetti, Bernardino, Gilbert, John R, Gilman, Sid, Giordani, Bruno, Glass, Jonathan D, Goate, Alison M, Green, Robert C, Growdon, John H, Hakonarson, Hakon, Hamilton, Ronald L, Hardy, John, Harrell, Lindy E, Head, Elizabeth, Honig, Lawrence S, and Huentelman, Matthew J
Subjects: Alzheimer's Disease Genetics Consortium, Temporal Lobe, Humans, Alzheimer Disease, Genetic Predisposition to Disease, RNA, Autopsy, Linear Models, Risk Factors, Gene Expression, Brain Chemistry, Genotype, Gene Dosage, Polymorphism, Single Nucleotide, Alleles, Aged, Female, Male, Apolipoprotein E4, Clinical Research, Alzheimer's Disease, Aging, Acquired Cognitive Impairment, Human Genome, Neurosciences, Dementia, Neurodegenerative, Genetics, Brain Disorders, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Aetiology, 2.1 Biological and endogenous factors, Neurological, Clinical Sciences, Cognitive Sciences, Neurology & Neurosurgery
Abstract: ObjectiveRecent genome-wide association studies (GWAS) of late-onset Alzheimer disease (LOAD) identified 9 novel risk loci. Discovery of functional variants within genes at these loci is required to confirm their role in Alzheimer disease (AD). Single nucleotide polymorphisms that influence gene expression (eSNPs) constitute an important class of functional variants. We therefore investigated the influence of the novel LOAD risk loci on human brain gene expression.MethodsWe measured gene expression levels in the cerebellum and temporal cortex of autopsied AD subjects and those with other brain pathologies (∼400 total subjects). To determine whether any of the novel LOAD risk variants are eSNPs, we tested their cis-association with expression of 6 nearby LOAD candidate genes detectable in human brain (ABCA7, BIN1, CLU, MS4A4A, MS4A6A, PICALM) and an additional 13 genes ±100 kb of these SNPs. To identify additional eSNPs that influence brain gene expression levels of the novel candidate LOAD genes, we identified SNPs ±100 kb of their location and tested for cis-associations.ResultsCLU rs11136000 (p = 7.81 × 10(-4)) and MS4A4A rs2304933/rs2304935 (p = 1.48 × 10(-4)-1.86 × 10(-4)) significantly influence temporal cortex expression levels of these genes. The LOAD-protective CLU and risky MS4A4A locus alleles associate with higher brain levels of these genes. There are other cis-variants that significantly influence brain expression of CLU and ABCA7 (p = 4.01 × 10(-5)-9.09 × 10(-9)), some of which also associate with AD risk (p = 2.64 × 10(-2)-6.25 × 10(-5)).ConclusionsCLU and MS4A4A eSNPs may at least partly explain the LOAD risk association at these loci. CLU and ABCA7 may harbor additional strong eSNPs. These results have implications in the search for functional variants at the novel LOAD risk loci.
Published: 2012

33. Evidence of novel fine-scale structural variation at autism spectrum disorder candidate loci

Author: Hedges, Dale J, Hamilton-Nelson, Kara L, Sacharow, Stephanie J, Nations, Laura, Beecham, Gary W, Kozhekbaeva, Zhanna M, Butler, Brittany L, Cukier, Holly N, Whitehead, Patrice L, Ma, Deqiong, Jaworski, James M, Nathanson, Lubov, Lee, Joycelyn M, Hauser, Stephen L, Oksenberg, Jorge R, Cuccaro, Michael L, Haines, Jonathan L, Gilbert, John R, and Pericak-Vance, Margaret A
Abstract: Abstract Background Autism spectrum disorders (ASD) represent a group of neurodevelopmental disorders characterized by a core set of social-communicative and behavioral impairments. Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain, acting primarily via the GABA receptors (GABR). Multiple lines of evidence, including altered GABA and GABA receptor expression in autistic patients, indicate that the GABAergic system may be involved in the etiology of autism. Methods As copy number variations (CNVs), particularly rare and de novo CNVs, have now been implicated in ASD risk, we examined the GABA receptors and genes in related pathways for structural variation that may be associated with autism. We further extended our candidate gene set to include 19 genes and regions that had either been directly implicated in the autism literature or were directly related (via function or ancestry) to these primary candidates. For the high resolution CNV screen we employed custom-designed 244 k comparative genomic hybridization (CGH) arrays. Collectively, our probes spanned a total of 11 Mb of GABA-related and additional candidate regions with a density of approximately one probe every 200 nucleotides, allowing a theoretical resolution for detection of CNVs of approximately 1 kb or greater on average. One hundred and sixty-eight autism cases and 149 control individuals were screened for structural variants. Prioritized CNV events were confirmed using quantitative PCR, and confirmed loci were evaluated on an additional set of 170 cases and 170 control individuals that were not included in the original discovery set. Loci that remained interesting were subsequently screened via quantitative PCR on an additional set of 755 cases and 1,809 unaffected family members. Results Results include rare deletions in autistic individuals at JAKMIP1, NRXN1, Neuroligin4Y, OXTR, and ABAT. Common insertion/deletion polymorphisms were detected at several loci, including GABBR2 and NRXN3. Overall, statistically significant enrichment in affected vs. unaffected individuals was observed for NRXN1 deletions. Conclusions These results provide additional support for the role of rare structural variation in ASD.
Published: 2012

34. Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease

Author: Naj, Adam C, Jun, Gyungah, Beecham, Gary W, Wang, Li-San, Vardarajan, Badri Narayan, Buros, Jacqueline, Gallins, Paul J, Buxbaum, Joseph D, Jarvik, Gail P, Crane, Paul K, Larson, Eric B, Bird, Thomas D, Boeve, Bradley F, Graff-Radford, Neill R, De Jager, Philip L, Evans, Denis, Schneider, Julie A, Carrasquillo, Minerva M, Ertekin-Taner, Nilufer, Younkin, Steven G, Cruchaga, Carlos, Kauwe, John SK, Nowotny, Petra, Kramer, Patricia, Hardy, John, Huentelman, Matthew J, Myers, Amanda J, Barmada, Michael M, Demirci, F Yesim, Baldwin, Clinton T, Green, Robert C, Rogaeva, Ekaterina, George-Hyslop, Peter St, Arnold, Steven E, Barber, Robert, Beach, Thomas, Bigio, Eileen H, Bowen, James D, Boxer, Adam, Burke, James R, Cairns, Nigel J, Carlson, Chris S, Carney, Regina M, Carroll, Steven L, Chui, Helena C, Clark, David G, Corneveaux, Jason, Cotman, Carl W, Cummings, Jeffrey L, DeCarli, Charles, DeKosky, Steven T, Diaz-Arrastia, Ramon, Dick, Malcolm, Dickson, Dennis W, Ellis, William G, Faber, Kelley M, Fallon, Kenneth B, Farlow, Martin R, Ferris, Steven, Frosch, Matthew P, Galasko, Douglas R, Ganguli, Mary, Gearing, Marla, Geschwind, Daniel H, Ghetti, Bernardino, Gilbert, John R, Gilman, Sid, Giordani, Bruno, Glass, Jonathan D, Growdon, John H, Hamilton, Ronald L, Harrell, Lindy E, Head, Elizabeth, Honig, Lawrence S, Hulette, Christine M, Hyman, Bradley T, Jicha, Gregory A, Jin, Lee-Way, Johnson, Nancy, Karlawish, Jason, Karydas, Anna, Kaye, Jeffrey A, Kim, Ronald, Koo, Edward H, Kowall, Neil W, Lah, James J, Levey, Allan I, Lieberman, Andrew P, Lopez, Oscar L, Mack, Wendy J, Marson, Daniel C, Martiniuk, Frank, Mash, Deborah C, Masliah, Eliezer, McCormick, Wayne C, McCurry, Susan M, McDavid, Andrew N, McKee, Ann C, Mesulam, Marsel, and Miller, Bruce L
Subjects: Biological Sciences, Genetics, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Alzheimer's Disease, Neurodegenerative, Human Genome, Acquired Cognitive Impairment, Aging, Dementia, Neurosciences, Brain Disorders, 2.1 Biological and endogenous factors, Neurological, Adaptor Proteins, Signal Transducing, Age of Onset, Aged, Aged, 80 and over, Alzheimer Disease, Antigens, CD, Antigens, Differentiation, Myelomonocytic, Cohort Studies, Cytoskeletal Proteins, Databases, Genetic, Female, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Humans, Male, Membrane Proteins, Multigene Family, Polymorphism, Single Nucleotide, Receptor, EphA1, Sialic Acid Binding Ig-like Lectin 3, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract: The Alzheimer Disease Genetics Consortium (ADGC) performed a genome-wide association study of late-onset Alzheimer disease using a three-stage design consisting of a discovery stage (stage 1) and two replication stages (stages 2 and 3). Both joint analysis and meta-analysis approaches were used. We obtained genome-wide significant results at MS4A4A (rs4938933; stages 1 and 2, meta-analysis P (P(M)) = 1.7 × 10(-9), joint analysis P (P(J)) = 1.7 × 10(-9); stages 1, 2 and 3, P(M) = 8.2 × 10(-12)), CD2AP (rs9349407; stages 1, 2 and 3, P(M) = 8.6 × 10(-9)), EPHA1 (rs11767557; stages 1, 2 and 3, P(M) = 6.0 × 10(-10)) and CD33 (rs3865444; stages 1, 2 and 3, P(M) = 1.6 × 10(-9)). We also replicated previous associations at CR1 (rs6701713; P(M) = 4.6 × 10(-10), P(J) = 5.2 × 10(-11)), CLU (rs1532278; P(M) = 8.3 × 10(-8), P(J) = 1.9 × 10(-8)), BIN1 (rs7561528; P(M) = 4.0 × 10(-14), P(J) = 5.2 × 10(-14)) and PICALM (rs561655; P(M) = 7.0 × 10(-11), P(J) = 1.0 × 10(-10)), but not at EXOC3L2, to late-onset Alzheimer's disease susceptibility.
Published: 2011

35. Neuropsychiatric features in a multi‐ethnic population with Alzheimer disease and mild cognitive impairment

Author: Celis, Katrina, primary, Zaman, Andrew, additional, Adams, Larry Deon, additional, Gardner, Olivia, additional, Farid, Rajabli, additional, Starks, Takiyah D., additional, Lacroix, Faina C., additional, Hamilton‐Nelson, Kara, additional, Mena, Pedro, additional, Tejada, Sergio, additional, Laux, Renee, additional, Song, Yeunjoo E., additional, Caban‐Holt, Allison, additional, Feliciano‐Astacio, Briseida, additional, Vance, Jeffery M., additional, Haines, Jonathan L., additional, Byrd, Goldie S., additional, Beecham, Gary W., additional, Pericak‐Vance, Margaret A., additional, and Cuccaro, Michael L., additional
Published: 2023
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36. LATE-NC risk alleles (in TMEM106B, GRN, and ABCC9 genes) among persons with African ancestry

Author: Katsumata, Yuriko, primary, Fardo, David W, additional, Shade, Lincoln M P, additional, Bowen, James D, additional, Crane, Paul K, additional, Jarvik, Gail P, additional, Keene, C Dirk, additional, Larson, Eric B, additional, McCormick, Wayne C, additional, McCurry, Susan M, additional, Mukherjee, Shubhabrata, additional, Kowall, Neil W, additional, McKee, Ann C, additional, Honig, Robert A, additional, Lawrence, S, additional, Vonsattel, Jean Paul, additional, Williamson, Jennifer, additional, Small, Scott, additional, Burke, James R, additional, Hulette, Christine M, additional, Welsh-Bohmer, Kathleen A, additional, Gearing, Marla, additional, Lah, James J, additional, Levey, Allan I, additional, Wingo, Thomas S, additional, Apostolova, Liana G, additional, Farlow, Martin R, additional, Ghetti, Bernardino, additional, Saykin, Andrew J, additional, Spina, Salvatore, additional, Albert, Marilyn S, additional, Lyketsos, Constantine G, additional, Troncoso, Juan C, additional, Frosch, Matthew P, additional, Green, Robert C, additional, Growdon, John H, additional, Hyman, Bradley T, additional, Tanzi, Rudolph E, additional, Potter, Huntington, additional, Dickson, Dennis W, additional, Ertekin-Taner, Nilufer, additional, Graff-Radford, Neill R, additional, Parisi, Joseph E, additional, Petersen, Ronald C, additional, Duara, Ranjan, additional, Buxbaum, Joseph D, additional, Goate, Alison M, additional, Sano, Mary, additional, Masurkar, Arjun V, additional, Wisniewski, Thomas, additional, Bigio, Eileen H, additional, Mesulam, Marsel, additional, Weintraub, Sandra, additional, Vassar, Robert, additional, Kaye, Jeffrey A, additional, Quinn, Joseph F, additional, Woltjer, Randall L, additional, Barnes, Lisa L, additional, Bennett, David A, additional, Schneider, Julie A, additional, Yu, Lei, additional, Henderson, Victor, additional, Fallon, Kenneth B, additional, Harrell, Lindy E, additional, Marson, Daniel C, additional, Roberson, Erik D, additional, DeCarli, Charles, additional, Jin, Lee-Way, additional, Olichney, John M, additional, Kim, Ronald, additional, LaFerla, Frank M, additional, Monuki, Edwin, additional, Head, Elizabeth, additional, Sultzer, David, additional, Geschwind, Daniel H, additional, Vinters, Harry V, additional, Chesselet, Marie-Francoise, additional, Galasko, Douglas R, additional, Brewer, James B, additional, Boxer, Adam, additional, Karydas, Anna, additional, Kramer, Joel H, additional, Miller, Bruce L, additional, Rosen, Howard J, additional, Seeley, William W, additional, Burns, Jeffrey M, additional, Swerdlow, Russell H, additional, Abner, Erin, additional, Van Eldik, Linda J, additional, Albin, Roger L, additional, Lieberman, Andrew P, additional, Paulson, Henry L, additional, Arnold, Steven E, additional, Trojanowski, John Q, additional, Van Deerlin, Vivianna M, additional, Hamilton, Ronald L, additional, Kamboh, M Ilyas, additional, Lopez, Oscar L, additional, Becker, James T, additional, Cao, Chuanhai, additional, Raj, Ashok, additional, Smith, Amanda G, additional, Chui, Helena C, additional, Miller, Carol A, additional, Ringman, John M, additional, Schneider, Lon S, additional, Bird, Thomas D, additional, Sonnen, Joshua A, additional, Yu, Chang-En, additional, Grabowski, Thomas, additional, Peskind, Elaine, additional, Raskind, Murray, additional, Li, Ge, additional, Tsuang, Debby W, additional, Asthana, Sanjay, additional, Atwood, Craig S, additional, Carlsson, Cynthia M, additional, Sager, Mark A, additional, Chin, Nathaniel A, additional, Craft, Suzanne, additional, Cairns, Nigel J, additional, Morris, John C, additional, Cruchaga, Carlos, additional, Strittmatter, Stephen, additional, Reiman, Eric M, additional, Beach, Thomas G, additional, Huentelman, Matthew J, additional, Hardy, John, additional, Myers, Amanda J, additional, Kauwe, John S K, additional, Hakonarson, Hakon, additional, Blacker, Deborah, additional, Montine, Thomas J, additional, Baldwin, Clinton T, additional, Farrer, Lindsay A, additional, Jun, Gyungah, additional, Lunetta, Kathryn L, additional, Bush, William S, additional, Haines, Jonathan L, additional, Lerner, Alan J, additional, Zhou, Xiongwei, additional, Barral, Sandra, additional, Reitz, Christiane, additional, Vardarajan, Badri N, additional, Mayeux, Richard, additional, Beecham, Gary W, additional, Carney, Regina M, additional, Cuccaro, Michael L, additional, Gilbert, John R, additional, Hamilton-Nelson, Kara L, additional, Kunkle, Brian W, additional, Martin, Eden R, additional, Pericak-Vance, Margaret A, additional, Vance, Jeffery M, additional, Cantwell, Laura B, additional, Kuzma, Amanda P, additional, Malamon, John, additional, Naj, Adam C, additional, Qu, Liming, additional, Schellenberg, Gerard D, additional, Valladares, Otto, additional, Wang, Li-San, additional, Zhao, Yi, additional, Leverenz, James B, additional, De Jager, Philip L, additional, Evans, Denis A, additional, Katz, Mindy J, additional, Lipton, Richard B, additional, Boeve, Bradley F, additional, Allen, Mariet, additional, Carrasquillo, Minerva M, additional, Younkin, Steven G, additional, Kukull, Walter A, additional, Faber, Kelley M, additional, Foroud, Tatiana M, additional, Pavlik, Valory, additional, Massman, Paul, additional, Darby, Eveleen, additional, Rodriguear, Monica, additional, Khaleeq, Aisha, additional, Royall, Donald R, additional, Stevens, Alan, additional, Ory, Marcia, additional, DeToledo, John C, additional, Wilms, Henrick, additional, Johnson, Kim, additional, Perez, Victoria, additional, Hernandez, Michelle, additional, Wilhelmsen, Kirk C, additional, Tilson, Jeffrey, additional, Chasse, Scott, additional, Barber, Robert C, additional, Fairchild, Thomas J, additional, O’Bryant, Sid E, additional, Knebl, Janice, additional, Hall, James R, additional, Johnson, Leigh, additional, Mains, Douglas, additional, Alvarez, Lisa, additional, Gamboa, Adriana, additional, Paydarfar, David, additional, Bertelson, John, additional, Woon, Martin, additional, Ayres, Gayle, additional, Aguirre, Alyssa, additional, Palmer, Raymond, additional, Polk, Marsha, additional, Adams, Perrie M, additional, Huebinger, Ryan M, additional, Reisch, Joan S, additional, Rosenberg, Roger N, additional, Cullum, Munro, additional, Williams, Benjamin, additional, Quiceno, Mary, additional, Hynan, Linda, additional, Smith, Janet, additional, Davis, Barb, additional, Nguyen, Trung, additional, Rogaeva, Ekaterina, additional, George-Hyslop, Peter St, additional, and Nelson, Peter T, additional
Published: 2023
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37. Multi-ancestry genome-wide meta-analysis of 56,241 individuals identifiesLRRC4C, LHX5-AS1and nominates ancestry-specific lociPTPRK,GRB14, andKIAA0825as novel risk loci for Alzheimer’s disease: the Alzheimer’s Disease Genetics Consortium

Author: Rajabli, Farid, primary, Benchek, Penelope, additional, Tosto, Giuseppe, additional, Kushch, Nicholas, additional, Sha, Jin, additional, Bazemore, Katrina, additional, Zhu, Congcong, additional, Lee, Wan-Ping, additional, Haut, Jacob, additional, Hamilton-Nelson, Kara L., additional, Wheeler, Nicholas R., additional, Zhao, Yi, additional, Farrell, John J., additional, Grunin, Michelle A., additional, Leung, Yuk Yee, additional, Kuksa, Pavel P., additional, Li, Donghe, additional, Lucio da Fonseca, Eder, additional, Mez, Jesse B., additional, Palmer, Ellen L., additional, Pillai, Jagan, additional, Sherva, Richard M., additional, Song, Yeunjoo E., additional, Zhang, Xiaoling, additional, Iqbal, Taha, additional, Pathak, Omkar, additional, Valladares, Otto, additional, Kuzma, Amanda B., additional, Abner, Erin, additional, Adams, Perrie M., additional, Aguirre, Alyssa, additional, Albert, Marilyn S., additional, Albin, Roger L., additional, Allen, Mariet, additional, Alvarez, Lisa, additional, Apostolova, Liana G., additional, Arnold, Steven E., additional, Asthana, Sanjay, additional, Atwood, Craig S., additional, Ayres, Gayle, additional, Baldwin, Clinton T., additional, Barber, Robert C., additional, Barnes, Lisa L., additional, Barral, Sandra, additional, Beach, Thomas G., additional, Becker, James T., additional, Beecham, Gary W., additional, Beekly, Duane, additional, Benitez, Bruno A., additional, Bennett, David, additional, Bertelson, John, additional, Bird, Thomas D., additional, Blacker, Deborah, additional, Boeve, Bradley F., additional, Bowen, James D., additional, Boxer, Adam, additional, Brewer, James, additional, Burke, James R., additional, Burns, Jeffrey M., additional, Buxbaum, Joseph D., additional, Cairns, Nigel J., additional, Cantwell, Laura B., additional, Cao, Chuanhai, additional, Carlson, Christopher S., additional, Carlsson, Cynthia M., additional, Carney, Regina M., additional, Carrasquillo, Minerva M., additional, Chasse, Scott, additional, Chesselet, Marie-Francoise, additional, Chin, Nathaniel A., additional, Chui, Helena C., additional, Chung, Jaeyoon, additional, Craft, Suzanne, additional, Crane, Paul K., additional, Cribbs, David H., additional, Crocco, Elizabeth A., additional, Cruchaga, Carlos, additional, Cuccaro, Michael L., additional, Cullum, Munro, additional, Darby, Eveleen, additional, Davis, Barbara, additional, De Jager, Philip L., additional, DeCarli, Charles, additional, DeToledo, John, additional, Dick, Malcolm, additional, Dickson, Dennis W., additional, Dombroski, Beth A., additional, Doody, Rachelle S., additional, Duara, Ranjan, additional, Ertekin-Taner, NIlüfer, additional, Evans, Denis A., additional, Faber, Kelley M., additional, Fairchild, Thomas J., additional, Fallon, Kenneth B., additional, Fardo, David W., additional, Farlow, Martin R., additional, Fernandez-Hernandez, Victoria, additional, Ferris, Steven, additional, Foroud, Tatiana M., additional, Frosch, Matthew P., additional, Fulton-Howard, Brian, additional, Galasko, Douglas R., additional, Gamboa, Adriana, additional, Gearing, Marla, additional, Geschwind, Daniel H., additional, Ghetti, Bernardino, additional, Gilbert, John R., additional, Goate, Alison M., additional, Grabowski, Thomas J., additional, Graff-Radford, Neill R., additional, Green, Robert C., additional, Growdon, John H., additional, Hakonarson, Hakon, additional, Hall, James, additional, Hamilton, Ronald L., additional, Harari, Oscar, additional, Hardy, John, additional, Harrell, Lindy E., additional, Head, Elizabeth, additional, Henderson, Victor W., additional, Hernandez, Michelle, additional, Hohman, Timothy, additional, Honig, Lawrence S., additional, Huebinger, Ryan M., additional, Huentelman, Matthew J., additional, Hulette, Christine M., additional, Hyman, Bradley T., additional, Hynan, Linda S., additional, Ibanez, Laura, additional, Jarvik, Gail P., additional, Jayadev, Suman, additional, Jin, Lee-Way, additional, Johnson, Kim, additional, Johnson, Leigh, additional, Kamboh, M. Ilyas, additional, Karydas, Anna M., additional, Katz, Mindy J., additional, Kauwe, John S., additional, Kaye, Jeffrey A., additional, Keene, C. Dirk, additional, Khaleeq, Aisha, additional, Kim, Ronald, additional, Knebl, Janice, additional, Kowall, Neil W., additional, Kramer, Joel H., additional, Kukull, Walter A., additional, LaFerla, Frank M., additional, Lah, James J., additional, Larson, Eric B., additional, Lerner, Alan, additional, Leverenz, James B., additional, Levey, Allan I., additional, Lieberman, Andrew P., additional, Lipton, Richard B., additional, Logue, Mark, additional, Lopez, Oscar L., additional, Lunetta, Kathryn L., additional, Lyketsos, Constantine G., additional, Mains, Douglas, additional, Margaret, Flanagan E., additional, Marson, Daniel C., additional, Martin, Eden R R., additional, Martiniuk, Frank, additional, Mash, Deborah C., additional, Masliah, Eliezer, additional, Massman, Paul, additional, Masurkar, Arjun, additional, McCormick, Wayne C., additional, McCurry, Susan M., additional, McDavid, Andrew N., additional, McDonough, Stefan, additional, McKee, Ann C., additional, Mesulam, Marsel, additional, Miller, Bruce L., additional, Miller, Carol A., additional, Miller, Joshua W., additional, Montine, Thomas J., additional, Monuki, Edwin S., additional, Morris, John C., additional, Mukherjee, Shubhabrata, additional, Myers, Amanda J., additional, Nguyen, Trung, additional, O’Bryant, Sid, additional, Olichney, John M., additional, Ory, Marcia, additional, Palmer, Raymond, additional, Parisi, Joseph E., additional, Paulson, Henry L., additional, Pavlik, Valory, additional, Paydarfar, David, additional, Perez, Victoria, additional, Peskind, Elaine, additional, Petersen, Ronald C., additional, Pierce, Aimee, additional, Polk, Marsha, additional, Poon, Wayne W., additional, Potter, Huntington, additional, Qu, Liming, additional, Quiceno, Mary, additional, Quinn, Joseph F., additional, Raj, Ashok, additional, Raskind, Murray, additional, Reiman, Eric M., additional, Reisberg, Barry, additional, Reisch, Joan S., additional, Ringman, John M., additional, Roberson, Erik D., additional, Rodriguear, Monica, additional, Rogaeva, Ekaterina, additional, Rosen, Howard J., additional, Rosenberg, Roger N., additional, Royall, Donald R., additional, Sager, Mark A., additional, Sano, Mary, additional, Saykin, Andrew J., additional, Schneider, Julie A., additional, Schneider, Lon S., additional, Seeley, William W., additional, Slifer, Susan H., additional, Small, Scott, additional, Smith, Amanda G., additional, Smith, Janet P., additional, Sonnen, Joshua A., additional, Spina, Salvatore, additional, St George-Hyslop, Peter, additional, Stern, Robert A., additional, Stevens, Alan B., additional, Strittmatter, Stephen M., additional, Sultzer, David, additional, Swerdlow, Russell H., additional, Tanzi, Rudolph E., additional, Tilson, Jeffrey L., additional, Trojanowski, John Q., additional, Troncoso, Juan C., additional, Tsuang, Debby W., additional, Van Deerlin, Vivianna M., additional, van Eldik, Linda J., additional, Vance, Jeffery M., additional, Vardarajan, Badri N., additional, Vassar, Robert, additional, Vinters, Harry V., additional, Vonsattel, Jean-Paul, additional, Weintraub, Sandra, additional, Welsh-Bohmer, Kathleen A., additional, Whitehead, Patrice L., additional, Wijsman, Ellen M., additional, Wilhelmsen, Kirk C., additional, Williams, Benjamin, additional, Williamson, Jennifer, additional, Wilms, Henrik, additional, Wingo, Thomas S., additional, Wisniewski, Thomas, additional, Woltjer, Randall L., additional, Woon, Martin, additional, Wright, Clinton B., additional, Wu, Chuang-Kuo, additional, Younkin, Steven G., additional, Yu, Chang-En, additional, Yu, Lei, additional, Zhu, Xiongwei, additional, Kunkle, Brian W., additional, Bush, William S., additional, Wang, Li-San, additional, Farrer, Lindsay A., additional, Haines, Jonathan L., additional, Mayeux, Richard, additional, Pericak-Vance, Margaret A., additional, Schellenberg, Gerard D., additional, Jun, Gyungah R., additional, Reitz, Christiane, additional, and Naj, Adam C., additional
Published: 2023
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38. African ancestryAPOEe4 non-carriers with higher educational attainment are resilient to Alzheimer disease pathology-specific blood biomarker pTau181

Author: Rajabli, Farid, primary, Seixas, Azizi A., additional, Akgun, Bilcag, additional, Adams, Larry D., additional, Inciute, Jovita, additional, Starks, Takiyah, additional, Laux, Renee, additional, Byrd, Goldie S, additional, Haines, Jonathan L, additional, Beecham, Gary W, additional, Vance, Jeffery M, additional, Cuccaro, Michael L, additional, and Pericak-Vance, Margaret A., additional
Published: 2023
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39. Transethnic genome-wide scan identifies novel Alzheimer's disease loci

Author: Adams, Perrie M., Albert, Marilyn S., Albin, Roger L., Apostolova, Liana G., Arnold, Steven E., Asthana, Sanjay, Atwood, Craig S., Barmada, Michjael M., Barnes, Lisa L., Beach, Thomas G., Becker, James T., Bigio, Eileen H., Bird, Thomas D., Blacker, Deborah, Boeve, Bradley F., Bowen, James D., Boxer, Adam, Burke, James R., Cairns, Nigel J., Cao, Chuanhai, Carlson, Chris S., Carlsson, Cynthia M., Carney, Regina M., Carrasquillo, Minerva M., Carroll, Steven L., Chui, Helena C., Clark, David G., Corneveaux, Jason, Cribbs, David H., Crocco, Elizabeth A., Cruchaga, Carlos, De Jager, Philip L., DeCarli, Charles, DeKosky, Steven T., Demirci, F. Yesim, Dick, Malcolm, Dickson, Dennis W., Doody, Rachelle S., Duara, Ranjan, Ertekin-Taner, Nilufer, Faber, Kelley M., Fairchild, Thomas J., Fallon, Kenneth B., Farlow, Martin R., Ferris, Steven, Frosch, Matthew P., Galasko, Douglas R., Gearing, Marla, Geschwind, Daniel H., Ghetti, Bernardino, Gilbert, John R., Glass, Jonathan D., Graff-Radford, Neill R., Green, Robert C., Growdon, John H., Hakonarson, Hakon, Hamilton, Ronald L., Hardy, John, Harrell, Lindy E., Head, Elizabeth, Honig, Lawrence S., Huebinger, Ryan M., Huentelman, Matthew J., Hulette, Christine M., Hyman, Bradley T., Jarvik, Gail P., Jicha, Gregory A., Jin, Lee-Way, Karydas, Anna, Kauwe, John S.K., Kaye, Jeffrey A., Kim, Ronald, Koo, Edward H., Kowall, Neil W., Kramer, Joel H., LaFerla, Frank M., Lah, James J., Leverenz, James B., Levey, Allan I., Li, Ge, Lieberman, Andrew P., Lin, Chiao-Feng, Lopez, Oscar L., Lyketsos, Constantine G., Mack, Wendy J., Marson, Daniel C., Martiniuk, Frank, Mash, Deborah C., Masliah, Eliezer, McCormick, Wayne C., McCurry, Susan M., McDavid, Andrew N., McKee, Ann C., Mesulam, Marsel, Miller, Bruce L., Miller, Carol A., Miller, Joshua W., Morris, John C., Mukherjee, Shubhabrata, Murrell, Jill R., Myers, Amanda J., O'Bryant, Sid, Olichney, John M., Pankratz, Vernon S., Parisi, Joseph E., Partch, Amanda, Paulson, Henry L., Perry, William, Peskind, Elaine, Petersen, Ronald C., Pierce, Aimee, Poon, Wayne W., Potter, Huntington, Quinn, Joseph F., Raj, Ashok, Raskind, Murray, Reisberg, Barry, Reisch, Joan S., Reitz, Christiane, Ringman, John M., Roberson, Erik D., Rogaeva, Ekaterina, Rosen, Howard J., Rosenberg, Roger N., Royall, Donald R., Sager, Mark A., Sano, Mary, Saykin, Andrew J., Schneider, Julie A., Schneider, Lon S., Seeley, William W., Smith, Amanda G., Sonnen, Joshua A., Spina, Salvatore, Stern, Robert A., Tanzi, Rudolph E., Thornton-Wells, Tricia A., Trojanowski, John Q., Troncoso, Juan C., Tsuang, Debby W., Van Deerlin, Vivianna M., Van Eldik, Linda J., Vardarajan, Badri N., Vinters, Harry V., Vonsattel, Jean Paul, Weintraub, Sandra, Welsh-Bohmer, Kathleen A., Williamson, Jennifer, Wishnek, Sarah, Woltjer, Randall L., Wright, Clinton B., Wu, Chuang-Kuo, Yu, Chang-En, Yu, Lei, Zhang, Xiaoling, Jun, Gyungah R., Chung, Jaeyoon, Mez, Jesse, Barber, Robert, Beecham, Gary W., Bennett, David A., Buxbaum, Joseph D., Byrd, Goldie S., Crane, Paul K., De Jager, Philip, Evans, Denis, Fallin, M. Danielle, Foroud, Tatiana M., Friedland, Robert P., Goate, Alison M., Hendrie, Hugh, Hall, Kathleen S., Hamilton-Nelson, Kara L., Inzelberg, Rivka, Kamboh, M. Ilyas, Kukull, Walter A., Kunkle, Brian W., Kuwano, Ryozo, Larson, Eric B., Logue, Mark W., Manly, Jennifer J., Martin, Eden R., Montine, Thomas J., Naj, Adam, Reiman, Eric M., Sherva, Richard, St. George-Hyslop, Peter H., Thornton, Timothy, Younkin, Steven G., Wang, Li-San, Wendlund, Jens R., Winslow, Ashley R., Haines, Jonathan, Mayeux, Richard, Pericak-Vance, Margaret A., Schellenberg, Gerard, Lunetta, Kathryn L., and Farrer, Lindsay A.
Published: 2017
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40. Late-onset vs nonmendelian early-onset Alzheimer disease: A distinction without a difference?

Author: Reitz, Christiane, Rogaeva, Ekaterina, and Beecham, Gary W.
Published: 2020
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41. Use of local genetic ancestry to assess TOMM40-523′ and risk for Alzheimer disease

Author: Bussies, Parker L., Rajabli, Farid, Griswold, Anthony, Dorfsman, Daniel A., Whitehead, Patrice, Adams, Larry D., Mena, Pedro R., Cuccaro, Michael, Haines, Jonathan L., Byrd, Goldie S., Beecham, Gary W., Pericak-Vance, Margaret A., Young, Juan I., and Vance, Jeffery M.
Published: 2020
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42. Genome-wide brain DNA methylation analysis suggests epigenetic reprogramming in Parkinson disease

Author: Young, Juan I., Sivasankaran, Sathesh K., Wang, Lily, Ali, Aleena, Mehta, Arpit, Davis, David A., Dykxhoorn, Derek M., Petito, Carol K., Beecham, Gary W., Martin, Eden R., Mash, Deborah C., Pericak-Vance, Margaret, Scott, William K., Montine, Thomas J., and Vance, Jeffery M.
Published: 2019
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43. Linkage of Alzheimer disease families with Puerto Rican ancestry identifies a chromosome 9 locus

Author: Rajabli, Farid, Feliciano-Astacio, Briseida E., Cukier, Holly N., Wang, Liyong, Griswold, Anthony J., Hamilton-Nelson, Kara L., Adams, Larry D., Rodriguez, Vanessa C., Mena, Pedro R., Tejada, Sergio, Celis, Katrina, Whitehead, Patrice L., Van Booven, Derek J., Hofmann, Natalia K., Bussies, Parker L., Prough, Michael, Chinea, Angel, Feliciano, Nereida I., Vardarajan, Badri N., Reitz, Christiane, Lee, Joseph H., Prince, Martin J., Jimenez, Ivonne Z., Mayeux, Richard P., Acosta, Heriberto, Dalgard, Clifton L., Haines, Jonathan L., Vance, Jeffery M., Cuccaro, Michael L., Beecham, Gary W., and Pericak-Vance, Margaret A.
Published: 2021
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44. Dissecting the role of Amerindian genetic ancestry and the ApoE ε4 allele on Alzheimer disease in an admixed Peruvian population

Author: Marca-Ysabel, Maria Victoria, Rajabli, Farid, Cornejo-Olivas, Mario, Whitehead, Patrice G., Hofmann, Natalia K., Illanes Manrique, Maryenela Zaida, Veliz Otani, Diego Martin, Milla Neyra, Ana Karina, Castro Suarez, Sheila, Meza Vega, Maria, Adams, Larry D., Mena, Pedro R., Rosario, Isasi, Cuccaro, Michael L., Vance, Jeffery M., Beecham, Gary W., Custodio, Nilton, Montesinos, Rosa, Mazzetti Soler, Pilar E., and Pericak-Vance, Margaret A.
Published: 2021
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45. Author Correction: Genomic evidence consistent with antagonistic pleiotropy may help explain the evolutionary maintenance of same-sex sexual behaviour in humans

Author: Zietsch, Brendan P., Sidari, Morgan J., Abdellaoui, Abdel, Maier, Robert, Långström, Niklas, Guo, Shengru, Beecham, Gary W., Martin, Eden R., Sanders, Alan R., and Verweij, Karin J. H.
Published: 2021
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46. The executive prominent/memory prominent spectrum in Alzheimer's disease is highly heritable

Author: Mez, Jesse, Mukherjee, Shubhabrata, Thornton, Timothy, Fardo, David W., Trittschuh, Emily, Sutti, Sheila, Sherva, Richard, Kauwe, John S., Naj, Adam C., Beecham, Gary W., Gross, Alden, Saykin, Andrew J., Green, Robert C., and Crane, Paul K.
Published: 2016
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47. Global and local ancestry in African-Americans: Implications for Alzheimer's disease risk

Author: Hohman, Timothy J., Cooke-Bailey, Jessica N., Reitz, Christiane, Jun, Gyungah, Naj, Adam, Beecham, Gary W., Liu, Zhi, Carney, Regina M., Vance, Jeffrey M., Cuccaro, Michael L., Rajbhandary, Ruchita, Vardarajan, Badri Narayan, Wang, Li-San, Valladares, Otto, Lin, Chiao-Feng, Larson, Eric B., Graff-Radford, Neill R., Evans, Denis, De Jager, Philip L., Crane, Paul K., Buxbaum, Joseph D., Murrell, Jill R., Raj, Towfique, Ertekin-Taner, Nilufer, Logue, Mark W., Baldwin, Clinton T., Green, Robert C., Barnes, Lisa L., Cantwell, Laura B., Fallin, M. Daniele, Go, Rodney C.P., Griffith, Patrick, Obisesan, Thomas O., Manly, Jennifer J., Lunetta, Kathryn L., Kamboh, M. Ilyas, Lopez, Oscar L., Bennett, David A., Hardy, John, Hendrie, Hugh C., Hall, Kathleen S., Goate, Alison M., Lang, Rosalyn, Byrd, Goldie S., Kukull, Walter A., Foroud, Tatiana M., Farrer, Lindsay A., Martin, Eden R., Pericak-Vance, Margaret A., Schellenberg, Gerard D., Mayeux, Richard, Haines, Jonathan L., and Thornton-Wells, Tricia A.
Published: 2016
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48. Genome-wide linkage analyses of non-Hispanic white families identify novel loci for familial late-onset Alzheimer's disease

Author: Kunkle, Brian W., Jaworski, James, Barral, Sandra, Vardarajan, Badri, Beecham, Gary W., Martin, Eden R., Cantwell, Laura S., Partch, Amanda, Bird, Thomas D., Raskind, Wendy H., DeStefano, Anita L., Carney, Regina M., Cuccaro, Michael, Vance, Jeffrey M., Farrer, Lindsay A., Goate, Alison M., Foroud, Tatiana, Mayeux, Richard P., Schellenberg, Gerard D., Haines, Jonathan L., and Pericak-Vance, Margaret A.
Published: 2016
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49. Rare genetic variation implicated in non-Hispanic white families with Alzheimer disease

Author: Beecham, Gary W., Vardarajan, Badri, Blue, Elizabeth, Bush, William, Jaworski, James, Barral, Sandra, DeStefano, Anita, Hamilton-Nelson, Kara, Kunkle, Brian, Martin, Eden R., Naj, Adam, Rajabli, Farid, Reitz, Christiane, Thornton, Timothy, van Duijn, Cornelia, Goate, Allison, Seshadri, Sudha, Farrer, Lindsay A., Boerwinkle, Eric, Schellenberg, Gerard, Haines, Jonathan L., Wijsman, Ellen, Mayeux, Richard, Pericak-Vance, Margaret A., English, Adam, Kalra, Divya, Muzny, Donna, Skinner, Evette, Doddapeneni, Harsha, Dinh, Huyen, Hu, Jianhong, Santibanez, Jireh, Jayaseelan, Joy, Worley, Kim, Bellair, Michelle, Gibbs, Richard A., Lee, Sandra, Dugan-Perez, Shannon, White, Simon, Korchina, Viktoriya, Nasser, Waleed, Salerno, William, Liu, Xiuping, Han, Yi, Zhu, Yiming, Liu, Yue, Khan, Ziad, Cupples, Adrienne, Beiser, Alexa, DeStefanos, Anita, Liu, Ching Ti, Sarnowski, Chloe, Satizabal, Claudia, Lancour, Dan, Patel, Devanshi, Sun, Fangui Jenny, Lin, Honghuang, Chung, Jaeyoon, Farrell, John, Dupuis, Josee, Lunetta, Kathy, Farrer, Lindsay, Seshadri, Sudha, Zhang, Xiaoling, Ma, Yiyi, Chen, Yuning, Banks, Eric, Gupta, Namrata, Choi, Seung Hoan, Gabriel, Stacey, Haines, Jonathan, Butkiewicz, Mariusz, Smieszek, Sandra, Bush, Will, Song, Yeunjoo, Vardarajan, Badri, Reitz, Christiane, Reyes, Dolly, Tosto, Giuseppe, De Jager, Phillip L, Mayeux, Richard, Barral, Sandra, Vanderspek, Ashley, van Duijn, Cornelia, Ikram, M Afran, Amin, Najaf, Amad, Shahzad, van der Lee, Sven, Faber, Kelley, Foroud, Tatiana, Schmidt, Helena, Schmidt, Reinhold, Renton, Alan, Goate, Alison, Marcora, Edoardo, Kapoor, Manav, Stine, Adam, Feolo, Michael, Launer, Lenore J., Bennett, David A, Xia, Li Charlie, Kunkle, Brian, Martin, Eden, Rajabli, Farid, Beecham, Gary, Jaworski, James, Hamilton-Nelson, Kara, Pericak-Vance, Margaret, Schmidt, Michael, Mosley, Thomas H., Kuzma, Amanda, Lin, Han-Jen, Qu, Liming, Wang, Micah Childress, Li-San, Valladares, Otto, Gangadharan, Prabhakaran, Cweibel, Rebecca, Zhao, Yi, Chou, Yi-Fan, Naj, Adam, Mlynarski, Elisabeth, Schellenberg, Gerard, Malamon, John, Cantwell, Laura, Zhang, Nancy, Wang, Weixin, Leung, Yuk Yee, Boerwinkle, Eric, Bressler, Jan, Below, Jennifer E., Fornage, Myriam, Liu, Xiaoming, Jian, Xueqiu, Nato, Alejandro Q, Jr., Horimoto, Andrea R, Wang, Bowen, Psaty, Bruce, Witten, Daniela, Tsuang, Debby, Blue, Elizabeth, Wijsman, Ellen, Sohi, Harkirat, Nguyen, Hiep, Bis, Joshua C., Rice, Kenneth, Brown, Lisa, Dorschner, Michael, Saad, Mohamad, Navas, Pat, Nafikov, Rafael, Thornton, Timothy, Day, Tyler, Cruchaga, Carlos, Koboldt, Daniel C., Larson, David E., Appelbaum, Elizabeth, Waligorski, Jason, Antonacci-Fulton, Lucinda, Wilson, Richard K., and Fulton, Robert S.
Published: 2018
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50. A haptoglobin (HP) structural variant alters the effect of APOE alleles on Alzheimer's disease.

Author: Bai, Haimeng, Naj, Adam C., Benchek, Penelope, Dumitrescu, Logan, Hohman, Timothy, Hamilton‐Nelson, Kara, Kallianpur, Asha R., Griswold, Anthony J., Vardarajan, Badri, Martin, Eden R., Beecham, Gary W., Below, Jennifer E., Schellenberg, Gerard, Mayeux, Richard, Farrer, Lindsay, Pericak‐Vance, Margaret A., Haines, Jonathan L., and Bush, William S.
Abstract: Background: Haptoglobin (HP) is an antioxidant of apolipoprotein E (APOE), and previous reports have shown HP binds with APOE and amyloid beta (Aβ) to aid its clearance. A common structural variant of the HP gene distinguishes it into two alleles: HP1 and HP2. Methods: HP genotypes were imputed in 29 cohorts from the Alzheimer's Disease Genetics Consortium (N = 20,512). Associations between the HP polymorphism and Alzheimer's disease (AD) risk and age of onset through APOE interactions were investigated using regression models. Results: The HP polymorphism significantly impacts AD risk in European‐descent individuals (and in meta‐analysis with African‐descent individuals) by modifying both the protective effect of APOE ε2 and the detrimental effect of APOE ε4. The effect is particularly significant among APOE ε4 carriers. Discussion: The effect modification of APOE by HP suggests adjustment and/or stratification by HP genotype is warranted when APOE risk is considered. Our findings also provided directions for further investigations on potential mechanisms behind this association. [ABSTRACT FROM AUTHOR]
Published: 2023
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784 results on '"Beecham, Gary W"'

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