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1. Genetic, transcriptomic, histological, and biochemical analysis of progressive supranuclear palsy implicates glial activation and novel risk genes

Author: Kurt Farrell, Jack Humphrey, Timothy Chang, Yi Zhao, Yuk Yee Leung, Pavel P. Kuksa, Vishakha Patil, Wan-Ping Lee, Amanda B. Kuzma, Otto Valladares, Laura B. Cantwell, Hui Wang, Ashvin Ravi, Claudia De Sanctis, Natalia Han, Thomas D. Christie, Robina Afzal, Shrishtee Kandoi, Kristen Whitney, Margaret M. Krassner, Hadley Ressler, SoongHo Kim, Diana Dangoor, Megan A. Iida, Alicia Casella, Ruth H. Walker, Melissa J. Nirenberg, Alan E. Renton, Bergan Babrowicz, Giovanni Coppola, Towfique Raj, Günter U. Höglinger, Ulrich Müller, Lawrence I. Golbe, Huw R. Morris, John Hardy, Tamas Revesz, Tom T. Warner, Zane Jaunmuktane, Kin Y. Mok, Rosa Rademakers, Dennis W. Dickson, Owen A. Ross, Li-San Wang, Alison Goate, Gerard Schellenberg, Daniel H. Geschwind, PSP Genetics Study Group, John F. Crary, and Adam Naj
Subjects: Science
Abstract: Abstract Progressive supranuclear palsy (PSP), a rare Parkinsonian disorder, is characterized by problems with movement, balance, and cognition. PSP differs from Alzheimer’s disease (AD) and other diseases, displaying abnormal microtubule-associated protein tau by both neuronal and glial cell pathologies. Genetic contributors may mediate these differences; however, the genetics of PSP remain underexplored. Here we conduct the largest genome-wide association study (GWAS) of PSP which includes 2779 cases (2595 neuropathologically-confirmed) and 5584 controls and identify six independent PSP susceptibility loci with genome-wide significant (P
Published: 2024
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2. Author Correction: Genetic, transcriptomic, histological, and biochemical analysis of progressive supranuclear palsy implicates glial activation and novel risk genes

Author: Kurt Farrell, Jack Humphrey, Timothy Chang, Yi Zhao, Yuk Yee Leung, Pavel P. Kuksa, Vishakha Patil, Wan-Ping Lee, Amanda B. Kuzma, Otto Valladares, Laura B. Cantwell, Hui Wang, Ashvin Ravi, Claudia De Sanctis, Natalia Han, Thomas D. Christie, Robina Afzal, Shrishtee Kandoi, Kristen Whitney, Margaret M. Krassner, Hadley Ressler, SoongHo Kim, Diana Dangoor, Megan A. Iida, Alicia Casella, Ruth H. Walker, Melissa J. Nirenberg, Alan E. Renton, Bergan Babrowicz, Giovanni Coppola, Towfique Raj, Günter U. Höglinger, Ulrich Müller, Lawrence I. Golbe, Huw R. Morris, John Hardy, Tamas Revesz, Tom T. Warner, Zane Jaunmuktane, Kin Y. Mok, Rosa Rademakers, Dennis W. Dickson, Owen A. Ross, Li-San Wang, Alison Goate, Gerard Schellenberg, Daniel H. Geschwind, PSP Genetics Study Group, John F. Crary, and Adam Naj
Subjects: Science
Published: 2024
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3. Vectorised spectral/hp element matrix-free operator for anisotropic heat transport in tokamak edge plasma

Author: Liu B, Cantwell CD, Moxey D, Mashy G, Sherwin SJ
Published: 2022
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4. Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease.

Author: Valentina Escott-Price, Céline Bellenguez, Li-San Wang, Seung-Hoan Choi, Denise Harold, Lesley Jones, Peter Holmans, Amy Gerrish, Alexey Vedernikov, Alexander Richards, Anita L DeStefano, Jean-Charles Lambert, Carla A Ibrahim-Verbaas, Adam C Naj, Rebecca Sims, Gyungah Jun, Joshua C Bis, Gary W Beecham, Benjamin Grenier-Boley, Giancarlo Russo, Tricia A Thornton-Wells, Nicola Denning, Albert V Smith, Vincent Chouraki, Charlene Thomas, M Arfan Ikram, Diana Zelenika, Badri N Vardarajan, Yoichiro Kamatani, Chiao-Feng Lin, Helena Schmidt, Brian Kunkle, Melanie L Dunstan, Maria Vronskaya, United Kingdom Brain Expression Consortium, Andrew D Johnson, Agustin Ruiz, Marie-Thérèse Bihoreau, Christiane Reitz, Florence Pasquier, Paul Hollingworth, Olivier Hanon, Annette L Fitzpatrick, Joseph D Buxbaum, Dominique Campion, Paul K Crane, Clinton Baldwin, Tim Becker, Vilmundur Gudnason, Carlos Cruchaga, David Craig, Najaf Amin, Claudine Berr, Oscar L Lopez, Philip L De Jager, Vincent Deramecourt, Janet A Johnston, Denis Evans, Simon Lovestone, Luc Letenneur, Isabel Hernández, David C Rubinsztein, Gudny Eiriksdottir, Kristel Sleegers, Alison M Goate, Nathalie Fiévet, Matthew J Huentelman, Michael Gill, Kristelle Brown, M Ilyas Kamboh, Lina Keller, Pascale Barberger-Gateau, Bernadette McGuinness, Eric B Larson, Amanda J Myers, Carole Dufouil, Stephen Todd, David Wallon, Seth Love, Ekaterina Rogaeva, John Gallacher, Peter St George-Hyslop, Jordi Clarimon, Alberto Lleo, Anthony Bayer, Debby W Tsuang, Lei Yu, Magda Tsolaki, Paola Bossù, Gianfranco Spalletta, Petra Proitsi, John Collinge, Sandro Sorbi, Florentino Sanchez Garcia, Nick C Fox, John Hardy, Maria Candida Deniz Naranjo, Paolo Bosco, Robert Clarke, Carol Brayne, Daniela Galimberti, Elio Scarpini, Ubaldo Bonuccelli, Michelangelo Mancuso, Gabriele Siciliano, Susanne Moebus, Patrizia Mecocci, Maria Del Zompo, Wolfgang Maier, Harald Hampel, Alberto Pilotto, Ana Frank-García, Francesco Panza, Vincenzo Solfrizzi, Paolo Caffarra, Benedetta Nacmias, William Perry, Manuel Mayhaus, Lars Lannfelt, Hakon Hakonarson, Sabrina Pichler, Minerva M Carrasquillo, Martin Ingelsson, Duane Beekly, Victoria Alvarez, Fanggeng Zou, Otto Valladares, Steven G Younkin, Eliecer Coto, Kara L Hamilton-Nelson, Wei Gu, Cristina Razquin, Pau Pastor, Ignacio Mateo, Michael J Owen, Kelley M Faber, Palmi V Jonsson, Onofre Combarros, Michael C O'Donovan, Laura B Cantwell, Hilkka Soininen, Deborah Blacker, Simon Mead, Thomas H Mosley, David A Bennett, Tamara B Harris, Laura Fratiglioni, Clive Holmes, Renee F A G de Bruijn, Peter Passmore, Thomas J Montine, Karolien Bettens, Jerome I Rotter, Alexis Brice, Kevin Morgan, Tatiana M Foroud, Walter A Kukull, Didier Hannequin, John F Powell, Michael A Nalls, Karen Ritchie, Kathryn L Lunetta, John S K Kauwe, Eric Boerwinkle, Matthias Riemenschneider, Mercè Boada, Mikko Hiltunen, Eden R Martin, Reinhold Schmidt, Dan Rujescu, Jean-François Dartigues, Richard Mayeux, Christophe Tzourio, Albert Hofman, Markus M Nöthen, Caroline Graff, Bruce M Psaty, Jonathan L Haines, Mark Lathrop, Margaret A Pericak-Vance, Lenore J Launer, Christine Van Broeckhoven, Lindsay A Farrer, Cornelia M van Duijn, Alfredo Ramirez, Sudha Seshadri, Gerard D Schellenberg, Philippe Amouyel, Julie Williams, and Cardiovascular Health Study (CHS)
Subjects: Medicine, Science
Abstract: BACKGROUND:Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. PRINCIPAL FINDINGS:In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4×10-6) and 14 (IGHV1-67 p = 7.9×10-8) which indexed novel susceptibility loci. SIGNIFICANCE:The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
Published: 2014
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5. The Edwards Aquifer Water Wars: The Final Chapter?

Author: Robert L. Gulley and Jenna B. Cantwell
Subjects: Edwards Aquifer, groundwater, Endangered Species Act, Habitat Conservation Plan, Water supply for domestic and industrial purposes, TD201-500
Abstract: On December 28, 2011, the Edwards Aquifer Authority’s Board of Directors approved the recommendations of the Edwards Aquifer Recovery Implementation Program with respect to a historic Habitat Conservation Plan. The Habitat Conservation Plan could resolve decades of acrimonious rancor and litigation over the use of the Edwards Aquifer. It provides the protection required by the federal Endangered Species Act for 8 listed species stemming from the use of the Edwards Aquifer and associated Comal and San Marcos springs while recognizing the region’s ever-growing need for water. The plan was developed by a diverse group of stakeholders through a consensus-based process and submitted to the U.S. Fish and Wildlife Service on January 5, 2012, in support of the Edwards Aquifer Recovery Implementation Program’s application for an Incidental Take Permit. The U.S. Fish and Wildlife Service noticed the availability of the Draft Environmental Impact Statement for public comment and conducted 7 public meetings to receive public comment. The public comment period closed on October 18, 2012. On February 15, 2013, the U. S. Fish and Wildlife Service issued its Record of Decision approving the issuance of the Incidental Take Permit and the Habitat Conservation Plan. This paper discusses the history of the dispute over the use of the aquifer, previous attempts to resolve the dispute, the strategic plan for protecting the aquifer, and the decision-making process used to develop the plan. Citation: Gulley RL, Cantwell JB. 2013. The Edwards Aquifer Water Wars: The Final Chapter? Texas Water Journal. 4(1):1-21. Available from: https://doi.org/10.21423/twj.v4i1.6423.
Published: 2013

6. LRP10 variants in progressive supranuclear palsy

Author: Leonie J.M. Vergouw, Li-San Wang, Guido J. Breedveld, Vincenzo Bonifati, Marialuisa Quadri, Gerard D. Schellenberg, Wang Z. Chiu, John C. van Swieten, Frank Jan de Jong, Adam C. Naj, Agnita J.W. Boon, Dennis W. Dickson, Shamiram Melhem, Owen A. Ross, Demy J.S. Kuipers, Elizabeth Mlynarksi, Laura Donker Kaat, Laura B. Cantwell, Neurology, and Clinical Genetics
Subjects: 0301 basic medicine, Male, Aging, medicine.medical_specialty, Disease, Article, Progressive supranuclear palsy, Cohort Studies, 03 medical and health sciences, symbols.namesake, 0302 clinical medicine, Internal medicine, Exome Sequencing, medicine, Humans, LDL-Receptor Related Proteins, Aged, Sanger sequencing, business.industry, Dementia with Lewy bodies, General Neuroscience, Genetic Variation, Exons, Middle Aged, medicine.disease, eye diseases, 030104 developmental biology, Cohort, symbols, Female, Neurology (clinical), Supranuclear Palsy, Progressive, Geriatrics and Gerontology, business, Validation cohort, 030217 neurology & neurosurgery, Developmental Biology
Abstract: The aim of this study was to explore whether variants in LRP10, recently associated with Parkinson's disease and dementia with Lewy bodies, are observed in 2 large cohorts (discovery and validation cohort) of patients with progressive supranuclear palsy (PSP). A total of 950 patients with PSP were enrolled: 246 patients with PSP (n = 85 possible (35%), n = 128 probable (52%), n = 33 definite (13%)) in the discovery cohort and 704 patients with definite PSP in the validation cohort. Sanger sequencing of all LRP10 exons and exon-intron boundaries was performed in the discovery cohort, and whole-exome sequencing was performed in the validation cohort. Two patients from the discovery cohort and 8 patients from the validation cohort carried a rare, heterozygous, and possibly pathogenic LRP10 variant (p.Gly326Asp, p.Asp389Asn, and p.Arg158His, p.Cys220Tyr, p.Thr278Ala, p.Gly306Asp, p.Glu486Asp, p.Arg554∗, p.Arg661Cys). In conclusion, possibly pathogenic LRP10 variants occur in a small fraction of patients with PSP and may be overrepresented in these patients compared with controls. This suggests that possibly pathogenic LRP10 variants may play a role in the development of PSP.
Published: 2020

7. Whole exome sequencing study identifies novel rare and common Alzheimer’s-Associated variants involved in immune response and transcriptional regulation

Author: Joshua C. Bis, Li-San Wang, Waleed Nasser, Giuseppe Tosto, Jean-Charles Lambert, Gary W. Beecham, Lucinda Fulton, Eric Boerwinkle, Reinhold Schmidt, Kara L. Hamilton-Nelson, Josée Dupuis, Cornelia M. van Duijn, Yuning Chen, Stéphanie Debette, Devanshi Patel, Philippe Amouyel, Gaël Nicolas, Farid Rajabli, Mark J. Daly, Richard Redon, Hilkka Soininen, Anita L. DeStefano, Aki S. Havulinna, Weixin Wang, Margaret A. Pericak-Vance, Chloé Sarnowski, Gerard D. Schellenberg, William S. Bush, Eden R. Martin, John J. Farrell, Richard A. Gibbs, Richard Mayeux, Emmanuelle Génin, Yi Zhao, Kwangsik Nho, Céline Bellenguez, Kari Mattila, Jean-François Deleuze, William J Salerno, Alzheimer’s Disease Sequencing, Brian W. Kunkle, Dominique Campion, Mikko Hiltunen, Richard K. Wilson, Sudha Seshadri, Paul K. Crane, Otto Valladares, Jennifer E. Below, Adam C. Naj, Timothy A. Thornton, Stacey Gabriel, Jan Konrad, Markus Perola, Mark Lathrop, Namrata Gupta, Badri N. Vardarajan, Bruce M. Psaty, Seppo Helisalmi, Jonathan L. Haines, Yiyi Ma, Honghuang Lin, Laura B. Cantwell, Carlos Cruchaga, Alan E. Renton, Terho Lehtimäki, Anne M. Remes, Michael A. Schmidt, Benjamin M. Neale, M. Arfan Ikram, Lindsay A. Farrer, Myriam Fornage, Daniel P. Howrigan, Ellen M. Wijsman, Mitja I. Kurki, Helena Schmidt, Aarno Palotie, Daniel Lancour, Camille Charbonnier, Daniela Witten, Liming Qu, Najaf Amin, Eric S. Lander, Alison Goate, Donna M. Muzny, Kathryn L. Lunetta, Jaakko Kaprio, Edoardo Marcora, Amanda B. Kuzma, Sven J. van der Lee, Shahzad Ahmad, Kim C. Worley, Christophe Tzourio, Benjamin Grenier-Boley, Jean-François Dartigues, L. Adrienne Cupples, Veikko Salomaa, Jaeyoon Chung, Christiane Reitz, Xueqiu Jian, Xiaoling Zhang, Olivier Quenez, Medicum, Institute for Molecular Medicine Finland, Complex Disease Genetics, University of Helsinki, Centre of Excellence in Complex Disease Genetics, Research Programs Unit, Aarno Palotie / Principal Investigator, Genomics of Neurological and Neuropsychiatric Disorders, HUS Helsinki and Uusimaa Hospital District, Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Rouen, Normandie Université (NU), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Centre National de Recherche en Génomique Humaine (CNRGH), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Epidemiology
Subjects: Male, 0301 basic medicine, DYSBINDIN GENE DTNBP1, Transcription, Genetic, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, SORL1, PROTEIN, Diseases, Genome-wide association study, SUSCEPTIBILITY, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, DISEASE, ABCA7, 0302 clinical medicine, Exome sequencing, Aged, 80 and over, Genetics, RISK, 3. Good health, Psychiatry and Mental health, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, Female, RNA, Long Noncoding, Alzheimer's disease, Immunoglobulin gene, EXPRESSION, Kruppel-Like Transcription Factors, Biology, Article, CODING MUTATIONS, 03 medical and health sciences, Cellular and Molecular Neuroscience, Apolipoproteins E, Alzheimer Disease, Exome Sequencing, medicine, Humans, GENOME-WIDE ASSOCIATION, Molecular Biology, Gene, Genotyping, Aged, Amyloid beta-Peptides, Polymorphism, Genetic, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], Haplotype, Immunity, 3112 Neurosciences, Correction, medicine.disease, 030104 developmental biology, Gene Expression Regulation, Haplotypes, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Immunoglobulin G, 3111 Biomedicine, 030217 neurology & neurosurgery
Abstract: The Alzheimer’s Disease Sequencing Project (ADSP) undertook whole exome sequencing in 5,740 late-onset Alzheimer disease (AD) cases and 5,096 cognitively normal controls primarily of European ancestry (EA), among whom 218 cases and 177 controls were Caribbean Hispanic (CH). An age-, sex- and APOE based risk score and family history were used to select cases most likely to harbor novel AD risk variants and controls least likely to develop AD by age 85 years. We tested ~1.5 million single nucleotide variants (SNVs) and 50,000 insertion-deletion polymorphisms (indels) for association to AD, using multiple models considering individual variants as well as gene-based tests aggregating rare, predicted functional, and loss of function variants. Sixteen single variants and 19 genes that met criteria for significant or suggestive associations after multiple-testing correction were evaluated for replication in four independent samples; three with whole exome sequencing (2,778 cases, 7,262 controls) and one with genome-wide genotyping imputed to the Haplotype Reference Consortium panel (9,343 cases, 11,527 controls). The top findings in the discovery sample were also followed-up in the ADSP whole-genome sequenced family-based dataset (197 members of 42 EA families and 501 members of 157 CH families). We identified novel and predicted functional genetic variants in genes previously associated with AD. We also detected associations in three novel genes: IGHG3 (p = 9.8 × 10−7), an immunoglobulin gene whose antibodies interact with β-amyloid, a long non-coding RNA AC099552.4 (p = 1.2 × 10−7), and a zinc-finger protein ZNF655 (gene-based p = 5.0 × 10−6). The latter two suggest an important role for transcriptional regulation in AD pathogenesis.
Published: 2018
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8. National outbreak of Salmonella serotype saintpaul infections: importance of Texas restaurant investigations in implicating jalapeño peppers.

Author: Rajal K Mody, Sharon A Greene, Linda Gaul, Adrianne Sever, Sarah Pichette, Ingrid Zambrana, Thi Dang, Angie Gass, René Wood, Karen Herman, Laura B Cantwell, Gerhard Falkenhorst, Kathleen Wannemuehler, Robert M Hoekstra, Isaac McCullum, Amy Cone, Lou Franklin, Jana Austin, Kristin Delea, Casey Barton Behravesh, Samir V Sodha, J Christopher Yee, Brian Emanuel, Sufian F Al-Khaldi, Val Jefferson, Ian T Williams, Patricia M Griffin, and David L Swerdlow
Subjects: Medicine, Science
Abstract: BACKGROUND: In May 2008, PulseNet detected a multistate outbreak of Salmonella enterica serotype Saintpaul infections. Initial investigations identified an epidemiologic association between illness and consumption of raw tomatoes, yet cases continued. In mid-June, we investigated two clusters of outbreak strain infections in Texas among patrons of Restaurant A and two establishments of Restaurant Chain B to determine the outbreak's source. METHODOLOGY/PRINCIPAL FINDINGS: We conducted independent case-control studies of Restaurant A and B patrons. Patients were matched to well controls by meal date. We conducted restaurant environmental investigations and traced the origin of implicated products. Forty-seven case-patients and 40 controls were enrolled in the Restaurant A study. Thirty case-patients and 31 controls were enrolled in the Restaurant Chain B study. In both studies, illness was independently associated with only one menu item, fresh salsa (Restaurant A: matched odds ratio [mOR], 37; 95% confidence interval [CI], 7.2-386; Restaurant B: mOR, 13; 95% CI 1.3-infinity). The only ingredient in common between the two salsas was raw jalapeño peppers. Cultures of jalapeño peppers collected from an importer that supplied Restaurant Chain B and serrano peppers and irrigation water from a Mexican farm that supplied that importer with jalapeño and serrano peppers grew the outbreak strain. CONCLUSIONS/SIGNIFICANCE: Jalapeño peppers, contaminated before arrival at the restaurants and served in uncooked fresh salsas, were the source of these infections. Our investigations, critical in understanding the broader multistate outbreak, exemplify an effective approach to investigating large foodborne outbreaks. Additional measures are needed to reduce produce contamination.
Published: 2011
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9. Fibrillation and molecular characteristics are coherent with clinical and pathological features of 4-repeat tauopathy caused by MAPT variant G273R

Author: Marla Gearing, Laura B. Cantwell, Helen Ling, John Hardy, Stefan Thor, Per Hammarström, Lea R'Bibo, Allan I. Levey, Kin Y. Mok, Tamas Revesz, Samuel P.S. Svensson, Nicholas W. Wood, Alexander Sandberg, Beth A. Dombroski, Josefin Fernius, Gerard D. Schellenberg, and Sofie Nyström
Subjects: 0301 basic medicine, 4-repeat tau, Biology, G273R, medicine.disease_cause, lcsh:RC321-571, Progressive supranuclear palsy, 03 medical and health sciences, 0302 clinical medicine, Basal Ganglia Diseases, Microtubule, mental disorders, MAPT, Pathology, medicine, Corticobasal degeneration, Animals, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Exome sequencing, Medicinsk genetik, Neurons, Mutation, Tauopathy, CBD, PSP, Aggregation propensity, Parkinsonism, Brain, medicine.disease, In vitro, Cell biology, 030104 developmental biology, Neurology, Tauopathies, Drosophila, Supranuclear Palsy, Progressive, Medical Genetics, Neuroglia, 030217 neurology & neurosurgery
Abstract: Microtubule Associated Protein Tau (MAPT) forms proteopathic aggregates in several diseases. The G273R tau mutation, located in the first repeat region, was found by exome sequencing in a patient who presented with dementia and parkinsonism. We herein return to pathological examination which demonstrated tau immunoreactivity in neurons and glia consistent of mixed progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) features. To rationalize the pathological findings, we used molecular biophysics to characterize the mutation in more detail in vitro and in Drosophila. The G273R mutation increases the aggregation propensity of 4-repeat (4R) tau and alters the tau binding affinity towards microtubules (MTs) and F-actin. Tau aggregates in PSP and CBD are predominantly 4R tau. Our data suggest that the G273R mutation induces a shift in pool of 4R tau by lower F-actin affinity, alters the conformation of MT bound 4R tau, while increasing chaperoning of 3R tau by binding stronger to F-actin. The mutation augmented fibrillation of 4R tau initiation in vitro and in glial cells in Drosophila and showed preferential seeding of 4R tau in vitro suggestively causing a late onset 4R tauopathy reminiscent of PSP and CBD. Funding Agencies|Karin & Sten Mortstedt CBD Solutions research grant [512385]; Swedish Research CouncilSwedish Research Council [201504521, 2019-04405]; Goran Gustafsson Foundation; Swedish Alzheimer Foundation; Swedish Brain foundation; Goizueta Alzheimers Disease Research Center at Emory University [NIH P50 AG025688]; UK Dementia Research Institute, from DRI Ltd.; UK Medical Research CouncilMedical Research Council UK (MRC); Alzheimers Society; Alzheimers Research UKAlzheimers Research UK (ARUK); Medical Research CouncilMedical Research Council UK (MRC) [MR/N026004/1]; Wellcome TrustWellcome Trust [202903/Z/16/Z]; Dolby Family Fund; National Institute for Health Research (NIHR) Biomedical Research Centre(BRC) at University College London Hospitals NHS Foundation TrustNational Institute for Health Research (NIHR); University College London; Michael J Fox Foundation; Michael J Fox Foundation.
Published: 2019

10. Novel Alzheimer Disease Risk Loci and Pathways in African American Individuals Using the African Genome Resources Panel

Author: James B. Brewer, Marilyn S. Albert, Bradley T. Hyman, Takiyah D. Starks, Russell H. Swerdlow, Jeffery M. Vance, Mary Sano, Gerard D. Schellenberg, Jennifer J. Manly, Walter A. Kukull, Jaeyoon Chung, Temitope Ayodele, Tatiana Foroud, Christiane Reitz, Thomas Wisniewski, Lindsay A. Farrer, Eric B. Larson, Laura B. Cantwell, David A. Bennett, Victor W. Henderson, Kara L. Hamilton-Nelson, Neill R. Graff-Radford, Hugh C. Hendrie, Denis A. Evans, Charles DeCarli, Scott A. Small, Joe D. Buxbaum, Paul K. Crane, M. Ilyas Kamboh, Robert Vassar, Suzanne Craft, M. Daniele Fallin, Richard Mayeux, Jonathan L. Haines, Melissa Jean-Francois, Izri Martinez, Thomas O. Obisesan, Li Sao Wang, John Q. Trojanowski, Jeffrey Kaye, Kathryn L. Lunetta, Frank M. LaFerla, Linda J. Van Eldik, Andrew J. Saykin, Bruce L. Miller, Lisa L. Barnes, Roger N. Rosenberg, John C. Morris, Michael A. Schmidt, Ronald C. Petersen, Eric M. Reiman, Kathleen S. Hall, Michael L. Cuccaro, Gyungah Jun, Goldie S. Byrd, Rodney C.P. Go, Oscar L. Lopez, Alison Goate, Margaret A. Pericak-Vance, Hans-Ulrich Klein, Jesse Mez, Brian W. Kunkle, Adam C. Naj, Thomas J. Grabowski, Eden R. Martin, Allan I. Levey, Larry D. Adams, Henry L. Paulson, James B. Leverenz, Stephen M. Strittmatter, Nilufer Ertekin-Taner, Todd E. Golde, Sanjay Asthana, Neil W. Kowall, Mark W. Logue, Amanda B. Kuzma, Helena C. Chui, and Phil De Jager
Subjects: Male, Apolipoprotein E, Genome-wide association study, Locus (genetics), 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, Humans, Medicine, Genetic Predisposition to Disease, 030212 general & internal medicine, Aged, Genetic association, Genetics, business.industry, TREM2, Correction, Middle Aged, medicine.disease, Black or African American, Genetic Loci, Meta-analysis, Etiology, Female, Neurology (clinical), Alzheimer's disease, business, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: Importance Compared with non-Hispanic White individuals, African American individuals from the same community are approximately twice as likely to develop Alzheimer disease. Despite this disparity, the largest Alzheimer disease genome-wide association studies to date have been conducted in non-Hispanic White individuals. In the largest association analyses of Alzheimer disease in African American individuals,ABCA7,TREM2, and an intergenic locus at 5q35 were previously implicated. Objective To identify additional risk loci in African American individuals by increasing the sample size and using the African Genome Resource panel. Design, Setting, and Participants This genome-wide association meta-analysis used case-control and family-based data sets from the Alzheimer Disease Genetics Consortium. There were multiple recruitment sites throughout the United States that included individuals with Alzheimer disease and controls of African American ancestry. Analysis began October 2018 and ended September 2019. Main Outcomes and Measures Diagnosis of Alzheimer disease. Results A total of 2784 individuals with Alzheimer disease (1944 female [69.8%]) and 5222 controls (3743 female [71.7%]) were analyzed (mean [SD] age at last evaluation, 74.2 [13.6] years). Associations with 4 novel common loci centered near the intracellular glycoprotein trafficking geneEDEM1(3p26;P = 8.9 × 10−7), near the immune response geneALCAM(3q13;P = 9.3 × 10−7), withinGPC6(13q31;P = 4.1 × 10−7), a gene critical for recruitment of glutamatergic receptors to the neuronal membrane, and withinVRK3(19q13.33;P = 3.5 × 10−7), a gene involved in glutamate neurotoxicity, were identified. In addition, several loci associated with rare variants, including a genome-wide significant intergenic locus nearIGF1Rat 15q26 (P = 1.7 × 10−9) and 6 additional loci with suggestive significance (P ≤ 5 × 10−7) such asAPI5 at 11p12 (P = 8.8 × 10−8) andRBFOX1at 16p13 (P = 5.4 × 10−7) were identified. Gene expression data from brain tissue demonstrate association ofALCAM, ARAP1, GPC6, andRBFOX1with brain β-amyloid load. Of 25 known loci associated with Alzheimer disease in non-Hispanic White individuals, onlyAPOE,ABCA7,TREM2,BIN1,CD2AP,FERMT2, andWWOXwere implicated at a nominal significance level or stronger in African American individuals. Pathway analyses strongly support the notion that immunity, lipid processing, and intracellular trafficking pathways underlying Alzheimer disease in African American individuals overlap with those observed in non-Hispanic White individuals. A new pathway emerging from these analyses is the kidney system, suggesting a novel mechanism for Alzheimer disease that needs further exploration. Conclusions and Relevance While the major pathways involved in Alzheimer disease etiology in African American individuals are similar to those in non-Hispanic White individuals, the disease-associated loci within these pathways differ.
Published: 2021
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11. P4‐044: THE GCAD CLOUD‐BASED WORKFLOW FOR PROCESSING WHOLE EXOME AND WHOLE GENOME DATA FROM THE ALZHEIMER'S DISEASE SEQUENCING PROJECT

Author: William J. Salerno, Yi-Fan Chou, Laura B. Cantwell, Adam C. Naj, John Malamon, Gerard D. Schellenberg, Liming Qu, Otto Valladares, Li-San Wang, Yi Zhao, Han-Jen Lin, Prabhakaran Gangadharan, Yuk Yee Leung, and Amanda B. Kuzma
Subjects: Epidemiology, Computer science, business.industry, Health Policy, Cloud computing, Computational biology, Disease, Genome, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Workflow, Developmental Neuroscience, Neurology (clinical), Geriatrics and Gerontology, business, Exome
Published: 2018
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12. P1‐149: THE ALZHEIMER'S DISEASE SEQUENCING PROJECT (ADSP) DATA UPDATE 2018

Author: Jason Waligorski, John J. Farrell, Eric Boerwinkle, Yuk Yee Leung, Laura B. Cantwell, Amanda B. Kuzma, Seung Hoan Choi, Sudha Seshadri, Elizabeth L. Appelbaum, Tatiana Foroud, Adam C. Naj, Namrata Gupta, Gerard D. Schellenberg, Kelley Faber, Otto Valladares, Joshua C. Bis, Li-San Wang, Liming Qu, Kara L. Hamilton-Nelson, Anita L. DeStefano, Yi Zhao, Donna M. Muzny, Briana Vogel, Robert S. Fulton, Dolly Reyes-Dumeyer, and William J Salerno
Subjects: Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, business.industry, Health Policy, Medicine, Neurology (clinical), Computational biology, Disease, Geriatrics and Gerontology, business
Published: 2018
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13. Convergent genetic and expression data implicate immunity in Alzheimer's disease

Author: John R. Gilbert, Simon Lovestone, Diana Zelenika, Walter A. Kukull, Peter Passmore, Chiao-Feng Lin, Nathalie Fievet, Brian W. Kunkle, Dominique Campion, Philip L. De Jager, Adam C. Naj, Kara L. Hamilton-Nelson, Lina Keller, Jean-Charles Lambert, Denise Harold, Paul K. Crane, John Powell, Kathryn L. Lunetta, Paolo Caffarra, Lei Yu, Anthony Bayer, Tricia A. Thornton-Wells, Christiane Reitz, Eric B. Larson, Florentino Sanchez Garcia, Lindsay A. Farrer, Charlene Thomas, Ekaterina Rogaeva, Victoria Alavarez, Alfredo Ramirez, Pascale Barberger-Gateau, Dan Rujescu, Paul Hollingworth, Margaret A. Pericak-Vance, Daniela Galimberti, J. Kornhuber, Alexey Vedernikov, Philippe Amouyel, Peter Holmans, Gianfranco Spalletta, Carole Dufouil, Wolfgang Maier, Patrick G. Kehoe, Florence Pasquier, Lesley Jones, Harald Hampel, Stephen Todd, Valur Emilsson, Pau Pastor, Manuel Mayhaus, Claudine Berr, Seth Love, Michelangelo Mancuso, Mikko Hiltunen, Simon Mead, Hilkka Soininen, Vincent Deramecourt, Bernadette McGuinness, Magda Tsolaki, Jean-François Dartigues, Jordi Clarimón, Marie-Thérèse Bihoreau, Laura Fratiglioni, Duane Beekly, Sabrina Pichler, Caroline Graff, Albert V. Smith, Nick C. Fox, Amy Gerrish, Karen Ritchie, Carlos Cruchaga, John Hardy, Benedetta Nacmias, Maria Candida Deniz Naranjo, Christine Van Broeckhoven, Laura B. Cantwell, Minerva M. Carrasquillo, Richard Mayeux, Karolien Bettens, Vincent Chouraki, Clive Holmes, Thomas H. Mosley, David C. Rubinsztein, Gyungah Jun, Anita L. DeStefano, Lenore J. Launer, Alexander Richards, Jerome I. Rotter, Lars Lannfelt, Annette L. Fitzpatrick, Fanggeng Zou, Joseph D. Buxbaum, Cristina Razquin, Mercè Boada, Najaf Amin, Palmi V. Jonsson, Martin Dichgans, Thomas J. Montine, Yoichiro Kamatani, Debby W. Tsuang, Alexis Brice, Hakon Hakonarson, John Collinge, Albert Hofman, Eden R. Martin, Oscar L. Lopez, Olivier Hanon, Melanie L. Dunstan, Kevin Morgan, Nicola Jones, Cornelia M. van Duijn, Valentina Escott-Price, Vilmundur Gudnason, Susanne Moebus, Peter St George-Hyslop, Michael Conlon O'Donovan, Michael Gill, Tim Becker, Markus M. Nöthen, Sandro Sorbi, Céline Bellenguez, Mike A. Nalls, Martin Ingelsson, Otto Valladares, Kristel Sleegers, Sudha Seshadri, Gerard D. Schellenberg, María J. Bullido, Patrizia Mecocci, Eric Boerwinkle, Michael John Owen, Helena Schmidt, Kristelle Brown, Julie Williams, Renée F.A.G. de Bruijn, Jonathan L. Haines, Mark Lathrop, Maria Del Zompo, Denis A. Evans, Rebecca Sims, Badri N. Vardarajan, John S. K. Kauwe, Luc Letteneur, Agustín Ruiz, David Craig, Steven G. Younkin, Bruce M. Psaty, Ignacio Mateo, Tatiana Foroud, David Wallon, P. Bosco, Alberti Lleò, Amanda J. Myers, Alberto Pilotto, Petra Proitsi, Reinhold Schmidt, Matthew J. Huentelman, David A. Bennett, Onofre Combarros, Kelley Faber, Gudny Eiriksdottir, M. Arfan Ikram, Lluís Tárraga, Francesco Panza, Carla A. Ibrahim-Verbaas, Joshua C. Bis, Li-San Wang, Matthias Riemenschneider, Gary W. Beecham, Alison Goate, Seung Hoan Choi, John Gallacher, Robert Clarke, Didier Hannequin, Deborah Blacker, Frank Jessen, Christophe Tzourio, Tamara B. Harris, Benjamin Grenier-Boley, Paola Bossù, Janet A. Johnston, M. Ilyas Kamboh, Giancarlo Russo, Timothy Stone, Carol Brayne, Eliecer Coto, French National Foundation on Alzheimer’s Disease and Related Disorders, Institut Pasteur, National Institutes of Health (US), Centre National de Genotypage (France), Fédération pour la Recherche sur le Cerveau (France), Erasmus University Rotterdam, Medical Research Council (UK), International Genomics of Alzheimer's Disease Consortium (IGAP), Neurology, and Epidemiology
Subjects: Pathway analysis, Epidemiology, ALIGATOR, Alzheimer's disease, Cholesterol metabolism, Dementia, Endocytosis, Immune response, Neurodegeneration, Ubiquitination, Weighted gene co-expression network analysis, Medizin, Genome-wide association study, genetics [Alzheimer Disease], Gene expression, Genetics, education.field_of_study, Health Policy, Brain, Single Nucleotide, 3. Good health, Psychiatry and Mental Health, Algorithms, Alzheimer Disease, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Genetic Predisposition to Disease, Developmental Neuroscience, Neurology (clinical), Geriatrics and Gerontology, Cellular and Molecular Neuroscience, Alzheimer’s disease, metabolism [Alzheimer Disease], Population, Genomics, Biology, Aligator, Article, Biological pathway, SDG 3 - Good Health and Well-being, medicine, ddc:610, Polymorphism, education, medicine.disease, Protein ubiquitination, metabolism [Brain], Human medicine
Abstract: © 2015, Elsevier Inc. All rights reserved. Background: Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis. Methods: The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results: ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 × 10-12 after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 × 10-11), cholesterol transport (P = 2.96 × 10-9), and proteasome-ubiquitin activity (P = 1.34 × 10-6). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P =.002-.05). Conclusions: The immune response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics., Medical Research Council, Alzheimer’s Research UK, and theWelsh Assembly Government. ADGC and CHARGE were supported by the National Institutes of Health, National Institute on Aging (NIH-NIA). CHARGE was also supported by Erasmus Medical Center and Erasmus University. IGAP was funded by the French National Foundation on Alzheimer’s Disease and Related Disorders, the Centre National de Genotypage and the Institut Pasteur de Lille, Inserm, FRC (Fondation pour la Recherche sur le Cerveau), and Rotary. This work has been developed and supported by the LABEX (Laboratory of Excellence Program Investment for the Future) DISTALZ grant (Development of Innovative Strategies for a Transdisciplinary approach to ALZheimer’s disease).
Published: 2015
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14. Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

Author: John Hardy, Nick C. Fox, Lena Lilius, Christine Van Broeckhoven, Mindy J. Katz, Carlos Cruchaga, Joshua W. Miller, Carol Brayne, Letizia Concari, Christopher Shaw, Minerva M. Carrasquillo, Richard Mayeux, Anne Boland, Charles DeCarli, Helena C. Chui, Laura B. Cantwell, Yoland Aladro Benito, Chuang Kuo Wu, Elaine R. Peskind, Andrew McDavid, M. Ilyas Kamboh, Amanda Smith, Pascual Sánchez-Juan, Jean-François Deleuze, Jayanadra J. Himali, Thomas H. Mosley, Thomas J. Montine, Chuanhai Cao, Andreas J. Forstner, Thomas G. Beach, Robert Barber, Miquel Aguilar, Liming Qu, Jerome I. Rotter, Matthew J. Huentelman, Christiane Reitz, Christopher J. O'Donnell, Steven G. Younkin, Bradley T. Hyman, Bruce L. Miller, Rachelle S. Doody, Eric B. Larson, Ronald L. Hamilton, Todd E. Golde, Steven E. Arnold, Melissa E. Garcia, Rachel Raybould, Lena Kilander, Mark A. Sager, Kevin Morgan, Kathryn L. Lunetta, William Perry, Joseph D. Buxbaum, Craig S. Atwood, Thomas D. Bird, Michael Conlon O'Donovan, Robert Olaso, Juan Fortea, Susanne Moebus, Lisa L. Barnes, Rachel Marshall, Huntington Potter, Mercè Boada, Shahzad Ahmad, Paolo Caffarra, Daniel C. Marson, Jonathan L. Haines, Perrie M. Adams, John M Olichney, Lars Lannfelt, Stefanie Heilmann-Heimbach, Markus M. Nöthen, Shubhabrata Mukherjee, John Malamon, Xue Wang, Christopher S. Carlson, Karen Ritchie, Roger N. Rosenberg, Paul K. Crane, Alexa S. Beiser, Céline Bellenguez, Robert C. Green, Maria Urbano, Petra Proitsi, John Powell, Elisa Majounie, Ammar Al-Chalabi, Hakon Hakonarson, Yogen Patel, Martin Scherer, Julie Williams, Richard B. Lipton, Vincent Dermecourt, Adam L. Boxer, Gerard D. Schellenberg, David G. Clark, Anita L. DeStefano, Joel H. Kramer, Victoria Alvarez, Nandini Badarinarayan, Oscar L. Lopez, Chris Corcoran, Ubaldo Bonuccelli, Donald R. Royall, James Bowen, Monica Diez Fairen, Tricia A. Thornton-Wells, Nilufer Ertekin-Taner, Florence Pasquier, Martin Ingelsson, Yi Zhao, John R. Gilbert, Valentina Escott-Price, Amanda B. Kuzma, Fabienne Garzia, Reinhard Heun, Otto Valladares, Andrew J. Saykin, Sara Ortega-Cubero, Liana G. Apostolova, Henry L. Paulson, John K Kauwe, Imelda Barber, Carolina Ceballos Diaz, Douglas Galasko, M. Arfan Ikram, Lluís Tárraga, Carlo Caltagirone, Joan S. Reisch, Wolfgang Maier, Bruno Vellas, Rebecca Sims, Angela Hodges, Matthew P. Frosch, Isabel Henández, Annakaisa Haapasalo, Thor Aspelund, Håkan Thonberg, Aimee Pierce, Roger L. Albin, Wayne W. Poon, Rebecca Sussams, Amy Braddel, Ranjan Duara, Albert V. Smith, Kirk C. Wilhelmsen, Gianfranco Spalletta, Simon Lovestone, Peter Passmore, Ana Frank-García, Cynthia M. Carlsson, Jade Chapman, Nathan D. Price, Philip L. De Jager, John M. Ringman, Seung Hoan Choi, Nicola Denning, Michael John Owen, Clinton T. Baldwin, Amalia C. Bruni, Denis A. Evans, Rudolph E. Tanzi, Dominique Campion, Laura Fratiglioni, Alberto Lleó, Per Hoffmann, Carole Dufouil, Charlotte Forsell, Alun Meggy, Charlene Thomas, Robert S. Stern, James B. Leverenz, Tatiana Foroud, William W. Seeley, James J. Lah, Brian A. Lawlor, Kenneth B. Fallon, Matthias Riemenschneider, Ryan M. Huebinger, Regina M. Carney, Clinton B. Wright, Didier Hannequin, Deborah Blacker, Anne Kinhult-Ståhlbom, Ekaterina Rogaeva, Andrew P. Lieberman, Bernardino Ghetti, Linda J. Van Eldik, Bernadette McGuinness, Thomas Fairchild, Margaret A. Pericak-Vance, Ashok Raj, Reinhold Schmidt, Ronald C. Petersen, Harald Hampel, María J. Bullido, Steven L. Carroll, Maria Candida Deniz Naranjo, Kathleen A. Welsh-Bohmer, Myriam Fornage, Joseph F. Quinn, Caroline Graff, Claudia L. Satizabal, Patrice L. Whitehead, David Wallon, Christopher Medway, Lindsay A. Farrer, Vilmundur Gudnason, Peter St George-Hyslop, Pau Pastor, Frank Jessen, Erin L. Abner, Johanna Jakobsdottir, Hieab H.H. Adams, Roberta Cecchetti, Walter A. Kukull, Thomas S. Wingo, Michelle K. Lupton, Valur Emilsson, Susan M. McCurry, Simon Mead, Hilkka Soininen, Sandra Weintraub, Amy Gerrish, Lindy E. Harrell, Lina Keller, Jean-Charles Lambert, Denise Harold, Stephen Todd, Wei Gu, Maura Gallo, Najaf Amin, Lenore J. Launer, Eleonora Sacchinelli, Mikko Hiltunen, Cécile Dulary, Eliecer Coto, Xueqiu Jian, Nathalie Fievet, Patrizia Mecocci, Sarah Taylor, Eric Boerwinkle, Maria Serpente, Ronald G. Munger, Ina Giegling, Carlo Masullo, Aoibhinn Lynch, Eliezer Masliah, Anne M. Koivisto, Chang En Yu, Qiong Yang, Benedetta Nacmias, Wayne C. McCormick, Kristelle Brown, Alessio Squassina, Deborah C. Mash, Brian W. Kunkle, Makrina Daniilidou, Alison Goate, David Carrell, Kara L. Hamilton-Nelson, Sandra Barral, Vincent Chouraki, Kristel Sleegers, Frank J. Wolters, Joseph E. Parisi, Iwona Kłoszewska, Ronald C. Kim, Sonia Moreno-Grau, Marina Arcaro, Carmen Muñoz Fernadez, Vernon S. Pankratz, Duane Beekly, Sabrina Pichler, Gislain Septier, Delphine Bacq, Amanda J. Myers, Adam C. Naj, Frank Martiniuk, Sudha Seshadri, Badri N. Vardarajan, Joshua A. Sonnen, M.-Marsel Mesulam, Howard J. Rosen, James T. Becker, Chiara Fenoglio, Ge Li, Alberto Pilotto, Mary Sano, Olivier Hanon, Honghuang Lin, Jean Paul G. Vonsattel, W. T. Longstreth, Daniela Galimberti, David C. Rubinsztein, RoseMarie Brundin, Vilmantas Giedraitis, Christine M. Hulette, Peter Holmans, Martin Dichgans, Maria Vronskaya, Céline Derbois, Michelangelo Mancuso, Constantine G. Lyketsos, Christophe Tzourio, Jacques Epelbaum, Raffaele Maletta, Mariet Allen, Hong-Dong Li, James R. Burke, Rik Vandenberghe, David G. Mann, Bruce M. Psaty, Lawrence S. Honig, Beth A. Dombroski, Erik D. Roberson, Cornelia M. van Duijn, Benjamin Grenier-Boley, Seppo Helisalmi, Jean-François Dartigues, Russell H. Swerdlow, Paola Bossù, Ashley R. Winslow, Elio Scarpini, Lesley Jones, Sebastien Engelborghs, John Q. Trojanowski, Jeffrey Kaye, Jenny Lord, Chiara Cupidi, Janet A. Johnston, Dan Rujescu, Feroze Golamaully, Anne Braae, Rafael Blesa, L. Adrienne Cupples, Dennis W. Dickson, Gail P. Jarvik, David W. Fardo, David H. Cribbs, Michael Gill, Jose Bras, Allan I. Levey, Jennifer Williamson, Rhodri Thomas, John C. Morris, Lei Yu, Debby W. Tsuang, Annette M. Hartmann, John H. Growdon, John Collinge, Claudine Berr, Fernando Rivadeneira, Oliver Peters, Albert Hofman, Frank M. LaFerla, Vivianna M. Van Deerlin, James Uphill, David A. Bennett, Onofre Combarros, Gudny Eiriksdottir, Jeremy D. Burgess, Melanie L. Dunstan, Elizabeth Crocco, Keeley J. Brookes, Robert R. Graham, Lon S. Schneider, Eden R. Martin, Matt Hill, Neill R. Graff-Radford, Joseph T. Hughes, Vincenzo Solfrizzi, Taniesha Morgan, Antonio Ciaramella, Bruno Dubois, Juan C. Troncoso, Paolo Bosco, Jordi Clarimón, Daniel H. Geschwind, Virginia Boccardi, Barry Reisberg, Timothy W. Behrens, Annette L. Fitzpatrick, Salvatore Spina, Alexis Brice, Eileen H. Bigio, Marla Gearing, Jeffrey M. Burns, Carol A. Miller, Marilyn S. Albert, Sven J. van der Lee, Sandro Sorbi, C. Dirk Keene, Daniel Levy, Antonio Daniele, Eric M. Reiman, Paramita Chakrabarty, Oscar Sotolongo-Grau, Helena Schmidt, Francesco Panza, Murray A. Raskind, Rita Guerreiro, Gyungah Jun, Anna Karydas, Markus Leber, Harry V. Vinters, Cory C. Funk, Charles C. White, Jill R. Murrell, Sid E. O'Bryant, Nigel J. Cairns, Josée Dupuis, Ann C. McKee, Julie A. Schneider, Megan L. Grove, Malcolm B. Dick, Bradley F. Boeve, Jennifer A. Brody, Sanjay Asthana, Agustín Ruiz, Stefan Herms, Yuning Chen, David Craig, Neil W. Kowall, Maria Donata Orfei, JoAnn T. Tschanz, Florentino Sanchez Garcia, Manuel Mayhaus, Alfredo Ramirez, James Turton, André G. Uitterlinden, Davide Seripa, Lee-Way Jin, Kelley Faber, Maria C. Norton, Shuo Li, Steven H. Ferris, Steffi G. Riedel-Heller, Joshua C. Bis, Li-San Wang, Johannes Kornhuber, Peter Paul De Deyn, Martin R. Farlow, Randall L. Woltjer, Gary W. Beecham, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Hospital of the University of Pennsylvania (HUP), Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Icelandic Heart Association [Kopavogur, Iceland] (IHA), John P. Hussman Institute for Human Genomics [Miami, FL, USA], University of Miami [Coral Gables], Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Department of Medicine, University of Washington [Seattle], Dr. John T. Macdonald Foundation [Miami, FL, USA] (Department of Human Genetics), Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Department of Genomics [Bonn, Germany] (Institute of Human Genetics), University of Bonn-Institute of Human Genetics [Bonn, Germany], Department of Molecular Genetics, Institut Català de Neurociències Aplicades [Barcelona, Spain], Well Advanced Solutions, Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Translational Centre for Regenerative Medicine (TRM), Department of Cell Therapy, Universität Leipzig [Leipzig]-Universität Leipzig [Leipzig], The University of Texas Health Science Center at Houston (UTHealth), Columbia University [New York], University of Eastern Finland, Life & Brain Center - Department of Genomics, Rheinische Friedrich-Wilhelms-Universität Bonn, Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), John P. Hussman Institute for Human Genomics, Neurobiologie de la Croissance et de la Senescence, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Emmy Noether Project (SFB 833), Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Boston University [Boston] (BU), Department of Genomics, Institute for Systems Biology [Seattle, WA, USA], Universitätsklinikum Bonn (UKB), Centre of Excellence for Robotic Vision [Canberra], Australian Research Council [Canberra] (ARC), Neuroscience and Mental Health Research Institute [Cardiff, UK] (School of Medicine), Boston University School of Medicine (BUSM), Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, University of Pennsylvania [Philadelphia], Section of Neuroscience and Clinical Pharmacology, University of Cagliari, Department of Epidemiology and Biostatistics, ERASMUS, Hospital Universitario Doctor Negrín [Las Palmas de Gran Canaria, Spain], Department of Neurodegenerative Diseases, University of Mississippi Medical Center (UMMC), Pathology and Laboratory Medicine [Philadelphia, PA, USA] (Penn Neurodegeneration Genomics Center), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Génétique du cancer et des maladies neuropsychiatriques (GMFC), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bioinformatics, GlaxoSmithKline, Aging Research Center [Karolinska Institutet] (ARC ), Stockholm University-Karolinska Institutet [Stockholm], University of Nottingham, UK (UON), University of Texas Health Science Center, Department of Neurobiology, Caring Sciences and Society (NVS), University of Bari Aldo Moro (UNIBA), Ageing Group, Centre for Public Health, Queen's University [Belfast] (QUB), Mayo Clinic [Jacksonville], Maurice Wohl Clinical Neuroscience Institut, King‘s College London, Istituto di Ricovero e Cura a Carattere Scientifico, Ospedale Casa Sollievo della Sofferenza [San Giovanni Rotondo] (IRCCS), Università degli Studi di Perugia (UNIPG), Framingham Heart Study, Boston University [Boston] (BU)-National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), CHU Rouen, Normandie Université (NU), Universidad Autonoma de Madrid (UAM), Centro de Investigacion Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III [Madrid] (ISC), National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), University of Florida [Gainesville] (UF), University of Parma = Università degli studi di Parma [Parme, Italie], Center for Cognitive Disorders AUSL [Parma, Italy], School of Public Health [Boston], Uppsala University, Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Université Pierre et Marie Curie - Paris 6 (UPMC), National Institute on Aging [Bethesda, USA] (NIA), National Institutes of Health [Bethesda] (NIH), Xi'an Jiaotong University (Xjtu), Department of Public health and Caring Sciences, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden, Institute of Gerontology and Geriatrics, Troubles cognitifs dégénératifs et vasculaires - U 1171 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Geriatric Medicine and Metabolic Diseases, Departments of Nuclear Medicine, University Medical Centre Hamburg-Eppendorf [Hamburg, Germany], University of Texas Southwestern Medical Center [Dallas], University of Cologne, Laboratoire d'Etudes et de Recherche en Informatique d'Angers (LERIA), Université d'Angers (UA), Johns Hopkins University (JHU), Universität Leipzig [Leipzig], University of Iceland [Reykjavik], Metacohorts Consortium, Harvard School of Public Health, Catholic University of Rome, Medical University Graz, Baylor College of Medicine (BCM), Baylor University, University of North Texas Health Science Center [Fort Worth], Santa Lucia Foundation (IRCCS), Nextel S.A. [Bilbao], Massachusetts General Hospital [Boston], Department of Pathology and Laboratory Medicine and Indiana Alzheimer disease Center, Indiana University School of Medicine, Indiana University System-Indiana University System, Joint Institute for the Study of the Atmosphere and Ocean (JISAO), Beijing University of Technology, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), Saul B. Korey Department of Neurology, Albert Einstein College of Medicine [New York]-Yeshiva University, Utah State University (USU), Fundació per la Recerca Biomèdica i Social Mútua Terrassa [Barcelona, Spain], Hospital Universitario Mutua de Terrassa, Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), Department of neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland, Department of neurology, University of Eastern Finland-University Hospital of Kuopio-University of Eastern Finland-University Hospital of Kuopio, Medical University of Łódź (MUL), University of Leicester, MRC Prion Unit, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, University of Milan, Fondazione Istituto di Ricerca e Cura Carattere Scientifico [Rome], Università degli Studi di Roma Tor Vergata [Roma], Saarland University Hospital, Universitat Autònoma de Barcelona (UAB), Regional Neurogenetic Centre [Lamezia Terme, Italy] (CRN - ASP Catanzaro), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Institute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, Universidade do Porto, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Experimental and Clinical Pharmacology, St. James Hospital and Trinity College [Dublin, Ireland], School of Medicine [Dublin], Trinity College Dublin, University of Sheffield [Sheffield], Lancaster University, University of Michigan [Ann Arbor], University of Michigan System, David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California-University of California, University of Wisconsin-Madison, Rush Alzheimer Disease Center [Chicago, IL, États-Unis], Rush University Medical Center [Chicago], Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), School of Engineering [Cardiff], Department of Psychiatry [Pittsburgh], University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), Northwestern University Feinberg School of Medicine, Mayo Clinic [Rochester], Swedish Medical Center [Seattle, WA, USA], University of California [San Francisco] (UCSF), University of California, Duke University [Durham], University of Kansas Medical Center [Lawrence], Laboratory of Molecular Neuropsychiatry, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Washington University in Saint Louis (WUSTL), University of South Florida [Tampa] (USF), Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Medical University of South Carolina [Charleston] (MUSC), University of Southern California (USC), Los Alamos National Laboratory (LANL), Centre de biologie du développement (CBD), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre de Biologie Intégrative (CBI), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Neurology Department, University of California, Davis (UCDavis-Neuro), University of California [Davis] (UC Davis), University of California [Irvine] (UCI), Mount Sinai Medical Center, Indiana State University, University of Alabama at Birmingham [ Birmingham] (UAB), University of Kentucky, New York University [New York] (NYU), NYU System (NYU), Department of Medical and Molecular Genetics, Department of Epidemiology and biostatistics, VU University Medical Center [Amsterdam], Emory University [Atlanta, GA], Department of Neurology, University of California-University of California-David Geffen School of Medicine [Los Angeles], Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), Department of Medical Genetics, HMNC Brain Health, Alzheimer Disease Research Laboratory, Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Oregon Health and Science University [Portland] (OHSU), Cleveland Clinic, Laboratoire d'Informatique, Systèmes, Traitement de l'Information et de la Connaissance (LISTIC), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Department of Psychiatry, School of Medicine-Johns Hopkins University and Johns Hopkins Bayview Medical Center, Douglas Mental Health University Institute [Montréal], McGill University = Université McGill [Montréal, Canada], Department of neurosciences, University of California [San Diego] (UC San Diego), Department of Physics and Astronomy [Fort Worth], Texas Christian University (TCU), Department of Computer Science [University of California, Davis], Indiana University System, Institute for Aging and Alzheimer’s Disease Research [Fort Worth] (IAADR), Department of Laboratory Medicine and Pathology, Mayo Clinic, Institute for Memory Impairments and Neurological Disorders [Irvine], University of Colorado Anschutz [Aurora], Tanz Center Research in Neurodegenerative Diseases [Toronto], University of Toronto, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Keck School of Medicine [Los Angeles], Indiana University [South Bend], Massachusetts General Hospital, Novartis Institutes for Biomedical Research [Cambridge, MA, USA], Departments of Pathology and Laboratory Medicine (Neuropathology) and Neurology, UCLA Medical Center-David Geffen School of Medicine [Los Angeles], University of California-University of California-University of California [Los Angeles] (UCLA), University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), Institut de Génomique d'Evry (IG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, University of Antwerp (UA), Institute Born-Bunge, Karolinska Institutet [Stockholm], Karolinska University Hospital [Stockholm], University of Kuopio, Centre Mémoire de Ressources et de Recherche [Lille-Bailleul] (CMRR), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Hôpital Roger Salengro [Lille], Laboratoire d'Analyse Génomique, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Inserm-U1167, Dpt Gériatrie [CHU Broca], AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Neuroépidémiologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Alzheimer Precision Medicine [CHU Pitié-Salpétriêre] (GRC 21 AMP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Department of Epidemiology, University of Washington, School of Medicine [Los Angeles], Albert Einstein College of Medicine [New York], IdiPAZ - Instituto de Investigación La Paz [Madrid, Spain], Instituto de Física Teórica UAM/CSIC (IFT), Universidad Autonoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Department of Internal Medicine, University of Central Asturias [Oviedo, Spain], Human Genome Sequencing Center, Baylor College of Medicine, Baylor University-Baylor University, Department of Epidemiology, Erasmus Medical Centre, Translational Genomics Research Institute [Phoenix, AZ, USA], University of Arizona, Banner Alzheimer's Institute [Phoenix, AZ, États-Unis], University of Texas Health Science Center at San Antonio [San Antonio], Mount Sinai School of Medicine, Department of Psychiatry-Icahn School of Medicine at Mount Sinai [New York] (MSSM), Department. of Neurological Sciences, University of Milan, IRCCS Ospedale Maggiore Policlinico, Centre for Research in Neurodegenerative Diseases, VA Puget Sound Health Care System/GRECC [Seattle, WA, USA], University of Pisa - Università di Pisa, Pfizer Worldwide Research and Development [Cambridge, MA, USA], Università cattolica del Sacro Cuore [Piacenza e Cremona] (Unicatt), Texas Tech University Health Sciences Center, Texas Tech University [Lubbock] (TTU), Saarland University [Saarbrücken], University of Bonn, Department of Public Health and Primary Care, University of Cambridge [UK] (CAM), Cambridge Institute for Medical Research (CIMR), Department of Molecular Neurosciences, Institute of Neurology, UCL, Institute of Psychiatry, Institute of psychiatry, University of British Columbia (UBC), the Clinical Neuroscience Research Group, University of Manchester [Manchester]-Greater Manchester Neurosciences Centre, Aristotle University of Thessaloniki, Memory and Dementia Centre, 3rd Department of Neurology, G. Pa, University of Barcelona, University of Southampton, Department of Psychiatry [Oxford] (POWIC), University of Oxford [Oxford]-The Warneford Hospital, School of Psychology [Cardiff University], Department of Medical Sciences, UCL, Institute of Neurology [London], Washington University School of Medicine, Netherlands Genomics Initiative, Netherlands Consortium for Healthy Aging [Leiden, Netherlands] (NCHA), School of Medecine, Center for Translational and Computational Neuroimmunology [New York, NY, États-Unis] (CTCN), Department of Neurology [New York, NY, États-Unis], Columbia University Medical Center (CUMC), Columbia University [New York]-Columbia University [New York]-Columbia University Medical Center (CUMC), Columbia University [New York]-Columbia University [New York], School of Life Sciences, Department of Neuroscience, Mayo Clinic Jacksonville, Icelandic Heart Association, Heart Preventive Clinic and Research Institute, Klinik für Psychiatrie, Martin-Luther-University Halle-Wittenberg, Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), The Center for Applied Genomics, Children’s Hospital of Philadelphia (CHOP ), Clínica Universidad de Navarra [Pamplona], Neurodegenerative Brain Diseases Group, VIB, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University-Medical Research Council, Brigham Young University (BYU), Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, The Gertrude H Sergivesky Center, Columbia University College of Physicians and Surgeons, Genetic Epidemiology Unit, Section of Clinical and Molecular Neurogenetics, Universität zu Lübeck [Lübeck], University of Pennsylvania - Department of Pathology & Laboratory Medecine, Framingham Heart Study [Framingham, MA, USA], ANR-10-IAHU-0006,IHU-A-ICM,Institut de Neurosciences Translationnelles de Paris(2010), European Project: 29845,LSH-ACC-MENTOR, University of Pennsylvania-University of Pennsylvania, Universität Bonn = University of Bonn-Institute of Human Genetics [Bonn, Germany], Universität Leipzig-Universität Leipzig, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), University of Pennsylvania, Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Università degli Studi di Perugia = University of Perugia (UNIPG), Universidad Autónoma de Madrid (UAM), Università degli studi di Parma = University of Parma (UNIPR), Institut de la Mémoire et de la Maladie d'Alzheimer [CHU Pitié-Salpétriêre] (IM2A), Université Pierre et Marie Curie - Paris 6 (UPMC)-CHU Pitié-Salpêtrière [AP-HP], Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Universität Leipzig, Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), Yeshiva University- Albert Einstein College of Medicine [New York], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Università degli Studi di Milano = University of Milan (UNIMI), Saarland University Hospital (UKS), Università degli Studi di Firenze = University of Florence (UniFI), Universidade do Porto = University of Porto, University of California (UC)-University of California (UC), University of California [San Francisco] (UC San Francisco), University of California (UC), University of Kansas Medical Center [Kansas City, KS, USA], Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), University of California [Irvine] (UC Irvine), University of Kentucky (UK), University of California (UC)-University of California (UC)-David Geffen School of Medicine [Los Angeles], Department of Computer Science [Univ California Davis] (CS - UC Davis), University of California (UC)-University of California (UC)-University of California [Los Angeles] (UCLA), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Groupe de recherche clinique Alzheimer Precision Medicine (GRC 21 - APM), Sorbonne Université (SU), Universidad Autónoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), University of Texas Health Science Center at San Antonio [San Antonio, Tx, USA], Universität Bonn = University of Bonn, University of Oxford-The Warneford Hospital, Medical Research Council-Cardiff University, Universität zu Lübeck = University of Lübeck [Lübeck], Epidemiology, Neurology, Gastroenterology & Hepatology, Internal Medicine, Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement (Inserm U1167 - RID-AGE - Institut Pasteur), Génétique, Reproduction et Développement - Clermont Auvergne (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Eberhard Karls Universität Tübingen, IRCCS 'Casa Sollievo della Sofferenza', Centro de Investigación Biomédica en Red para Enfermedades Neurodegenerativas (Ciberned), University of Florida [Gainesville], University of Parma, Troubles cognitifs dégénératifs et vasculaires (U1171), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-INSERM, Yeshiva University- Albert Einstein College of Medicine, Institut d’Électronique, de Microélectronique et de Nanotechnologie (IEMN) - UMR 8520 (IEMN), Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Université Polytechnique Hauts-de-France (UPHF)-Ecole Centrale de Lille-Université Polytechnique Hauts-de-France (UPHF)-Institut supérieur de l'électronique et du numérique (ISEN), Autonomous University of Barcelona (UAB), Università degli Studi di Firenze [Firenze], Universidade do Porto [Porto], Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Washington University in St Louis, University of South Florida (USF), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, McGill University, Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Centre National de la Recherche Scientifique (CNRS), Neuropsychiatrie : recherche épidémiologique et clinique, Alzheimer Precision Medicine GRC n°21 (APM), CHU Pitié-Salpêtrière [APHP], Albert Einstein College of Medicine, Universidad Autonoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Spain] (CSIC), Università Cattolica del S. Cuore - Catholic University of the Sacred Hearth, University of Florence (UNIFI), CIBER de Enfermedades Neurodegenerativas (CIBERNED), Universität zu Lübeck [Lübeck] - University of Lübeck [Lübeck], [ANR-10-IAIHU-06],« Investissements d'avenir » ,Agence nationale de la recherche (ANR), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Icahn School of Medicine at Mount Sinai [New York] (MSSM)-Department of Psychiatry, van der Lee, Sven J [0000-0003-1606-8643], Naj, Adam C [0000-0002-9621-2942], Badarinarayan, Nandini [0000-0002-6944-748X], Chouraki, Vincent [0000-0002-4698-1794], Graham, Robert R [0000-0001-7151-4277], Hoffmann, Per [0000-0002-6573-983X], Smith, Albert V [0000-0003-1942-5845], Satizabal, Claudia L [0000-0002-1115-4430], Brody, Jennifer A [0000-0001-8509-148X], Wolters, Frank J [0000-0003-2226-4050], Lupton, Michelle K [0000-0002-7274-7299], Lin, Honghuang [0000-0003-3043-3942], Adams, Hieab H [0000-0003-3687-2508], Giedraitis, Vilmantas [0000-0003-3423-2021], Pasquier, Florence [0000-0001-9880-9788], Chen, Yuning [0000-0002-7358-7055], Bossù, Paola [0000-0002-1432-0078], Ghetti, Bernardino [0000-0002-1842-8019], Yang, Qiong [0000-0002-3658-1375], Aspelund, Thor [0000-0002-7998-5433], Bullido, María J [0000-0002-6477-1117], Rivadeneira, Fernando [0000-0001-9435-9441], Rubinsztein, David C [0000-0001-5002-5263], Al-Chalabi, Ammar [0000-0002-4924-7712], Tsolaki, Magda [0000-0002-2072-8010], De Jager, Philip L [0000-0002-8057-2505], Dickson, Dennis W [0000-0001-7189-7917], Van Broeckhoven, Christine [0000-0003-0183-7665], Ikram, M Arfan [0000-0003-0372-8585], Amouyel, Philippe [0000-0001-9088-234X], Lambert, Jean-Charles [0000-0003-0829-7817], Apollo - University of Cambridge Repository, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Alzheimer Precision Medicine [CHU Pitié-Salpétriêre] (GRC 21 APM), Berr, Claudine, Institut de Neurosciences Translationnelles de Paris - - IHU-A-ICM2010 - ANR-10-IAHU-0006 - IAHU - VALID, and Mentoring of LifeSciHealth-Multipliers in the Accession Candidate Countries - LSH-ACC-MENTOR - 29845 - OLD
Subjects: 0301 basic medicine, Linkage disequilibrium, [SDV]Life Sciences [q-bio], Medizin, Sequence Homology, Genome-wide association study, genetics [Alzheimer Disease], metabolism [Microglia], Linkage Disequilibrium, 0302 clinical medicine, genetics [Protein Interaction Maps], genetics [Membrane Glycoproteins], Gene Frequency, Immunologic, genetics [Adaptor Proteins, Signal Transducing], Receptors, genetics [Exome], Odds Ratio, Innate, genetics [Receptors, Immunologic], Exome, Protein Interaction Maps, genetics [Genetic Predisposition to Disease], Receptors, Immunologic, ABI3 protein, human, Genetics, Adaptor Proteins, Signal Transducing, Alzheimer Disease, Amino Acid Sequence, Case-Control Studies, Gene Expression Profiling, Genetic Predisposition to Disease, Genotype, Humans, Immunity, Innate, Membrane Glycoproteins, Microglia, Phospholipase C gamma, Sequence Homology, Amino Acid, Polymorphism, Single Nucleotide, Adaptor Proteins, Single Nucleotide, 3. Good health, [SDV] Life Sciences [q-bio], Amino Acid, Settore MED/26 - NEUROLOGIA, genetics [Phospholipase C gamma], [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Alzheimer's disease, Common disease-common variant, Biology, Article, 03 medical and health sciences, ddc:570, medicine, Journal Article, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Polymorphism, Allele frequency, TREM2 protein, human, TREM2, Case-control study, Signal Transducing, Immunity, medicine.disease, R1, Minor allele frequency, genetics [Immunity, Innate], 030104 developmental biology, Human medicine, 030217 neurology & neurosurgery
Abstract: International audience; 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
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15. [P3–090]: THE ALZHEIMER's DISEASE SEQUENCING PROJECT (ADSP) DATA UPDATE 2017

Author: Rebecca Cweibel, Elizabeth L. Appelbaum, John J. Farrell, Robert S. Fulton, Otto Valladares, Sudha Seshadri, Eric Boerwinkle, Laura B. Cantwell, Tatiana Foroud, Adam C. Naj, Seung Hoan Choi, Namrata Gupta, Liming Qu, Jason Waligorski, Mike Feolo, Gerard D. Schellenberg, Kara L. Hamilton-Nelson, Yuk Yee Leung, Amanda B. Kuzma, Anita L. DeStefano, Han-Jen Lin, Adam Stine, Dolly Reyes-Dumeyer, William J Salerno, Donna M. Muzny, Joshua C. Bis, Li-San Wang, and Kelley Faber
Subjects: Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, business.industry, Health Policy, Medicine, Neurology (clinical), Computational biology, Disease, Geriatrics and Gerontology, business
Published: 2017
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16. VCPA: genomic variant calling pipeline and data management tool for Alzheimer’s Disease Sequencing Project

Author: Laura B. Cantwell, Alzheimer’s Disease Sequencing, Yi-Fan Chou, Otto Valladares, Li-San Wang, Gerard D. Schellenberg, Prabhakaran Gangadharan, Liming Qu, Han-Jen Lin, Yuk Yee Leung, Amanda B. Kuzma, and William J Salerno
Subjects: 0301 basic medicine, Statistics and Probability, Source code, Computer science, Data management, media_common.quotation_subject, 0206 medical engineering, Genomics, 02 engineering and technology, computer.software_genre, Genome, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, Humans, Indel, Molecular Biology, Exome sequencing, Data Management, media_common, 030304 developmental biology, 0303 health sciences, Database, business.industry, Process (computing), High-Throughput Nucleotide Sequencing, Applications Notes, Pipeline (software), Computer Science Applications, Computational Mathematics, 030104 developmental biology, Computational Theory and Mathematics, 030220 oncology & carcinogenesis, Corrigendum, business, Sequence Analysis, computer, Software, 020602 bioinformatics, 030217 neurology & neurosurgery
Abstract: Summary: We report VCPA, our SNP/Indel Variant Calling Pipeline and data management tool used for analysis of whole genome and exome sequencing (WGS/WES) for the Alzheimer’s Disease Sequencing Project. VCPA consists of two independent but linkable components: pipeline and tracking database. The pipeline is coded in Workflow Description Language and is fully optimized for the Amazon elastic compute cloud environment. This includes steps for processing raw sequence reads including read alignment, and all the way up to variant calling using GATK. The tracking database allows users to dynamically view the statuses of jobs running and the quality metrics reported by the pipeline. Users can thus monitor the production process and diagnose if any problem arises during the procedure. All quality metrics (>100 collected per processed genome) are stored in the database, thus facilitating users to compare, share and visualize the results. To summarize, VCPA is functional equivalent to the CCDG/TOPMed pipeline. Together with the dockerized database (also available as Amazon Machine Image), users can easily process any WGS/WES data on Amazon cloud with minimal installation.Availability: VCPA is released under the MIT license and is available for academic and nonprofit use for free. The pipeline source code and step-by-step instructions are available from the National Institute on Aging Genetics of Alzheimer’s Disease Data Storage Site (http://www.niagads.org/VCPA).Contact:yyee@pennmedicine.upenn.edu or lswang@pennmedicine.upenn.eduSupplementary information: Supplementary data are available at Bioinformatics online.
Published: 2019
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17. F1‐01‐02: Alzheimer's Disease Sequencing Project: Search for Alzheimer's Disease Resilience Genes That May Modify Disease Susceptibility in Specific Apoe Genotype Backgrounds

Author: Marilyn M. Miller, Adam C. Naj, Joshua C. Bis, Li-San Wang, Gary W. Beecham, Richard Mayeux, Myriam Fornage, Manav Kapoor, Gerard D. Schellenberg, Adam Felsenfeld, Alison Goate, Eric Boerwinkle, Alan E. Renton, Eduardo Marcora, Margaret A. Pericak-Vance, Mugdha Khaladkar, Badri N. Vardarajan, Yiyi Ma, Keoni Kauwe, Sudha Seshadri, Laura B. Cantwell, Amanda Partch, Rebecca Cweibel, Dan Kobolt, Carlos Cruchaga, and Lindsay A. Farrer
Subjects: Apolipoprotein E, Genetics, Epidemiology, Health Policy, Disease, Biology, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Disease susceptibility, Developmental Neuroscience, Genotype, Neurology (clinical), Geriatrics and Gerontology, Resilience (network), Gene
Published: 2016
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18. P2‐097: The Alzheimer’s Disease Sequencing Project (ADSP): Data Production, Management, and Availability

Author: Seung Hoan Choi, Rebecca Cweibel, Tatiana Foroud, Amanda Partch, Mike Feolo, Daniel Micah Childress, Dan Kobolt, Sudha Seshadri, Eric Boerwinkle, Otto Valladares, Prabhakaran Gangadharan, Shannon Stiening, Gerard D. Schellenberg, Kelley Faber, Laura B. Cantwell, Joshua C. Bis, Li-San Wang, Shannon Dugan-Rocha, Namrata Gupta, Anita L. DeStefano, Adam Stine, Dolly Reyes-Dumeyer, and William J Salerno
Subjects: 0301 basic medicine, Epidemiology, business.industry, Health Policy, Disease, Biology, Bioinformatics, Biotechnology, 03 medical and health sciences, Psychiatry and Mental health, Cellular and Molecular Neuroscience, 030104 developmental biology, 0302 clinical medicine, Developmental Neuroscience, Production manager, Neurology (clinical), Geriatrics and Gerontology, business, 030217 neurology & neurosurgery
Published: 2016
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19. Common genetic variants in the CLDN2 and PRSS1-PRSS2 loci alter risk for alcohol-related and sporadic pancreatitis

Author: Marla Gearing, David G. Clark, Steven L. Carroll, Marianne Johnstone, Darwin L. Conwell, Gregory A. Cote, Sandra Weintraub, Matthew P. Frosch, Stuart Sherman, Badri N. Vardarajan, Joshua A. Sonnen, Lindy E. Harrell, Peter B. Cotton, Lisa L. Barnes, Lawrence S. Honig, Carol A. Miller, Adam Slivka, Michelle A. Anderson, Nadine M. Melhem, David A. Bennett, Joel H. Kramer, Jill P. Smith, Michele D. Lewis, Mary Ganguli, Jean Paul Vonsatte, Thomas J. Montine, Lee-Way Jin, Kenneth B. Fallon, Marilyn S. Albert, Eliezer Masliah, John H. Growdon, Barry Reisberg, Chuanhai Cao, Patricia L. Kramer, Douglas J. Hartman, Allan I. Levey, Jennifer Williamson, Vivianna M. Van Deerlin, Wayne W. Poon, Alison Goate, Vijay P. Singh, Bernie Devlin, Christiane Reitz, Ann C. McKee, Amanda Smith, Neill R. Graff-Radford, Walter A. Kukul, John Baillie, Andres Gelrud, Ranjan Duara, Thomas D. Bird, Clinton B. Wright, Deborah Blacker, Chiao-Feng Lin, Ge Li, Ronald C. Kim, Deborah C. Mash, Debby W. Tsuang, John P. Neoptolemos, Timothy B. Gardner, Kathryn L. Lunetta, Steven G. Younkin, Kara L. Hamilton-Nelson, Ronald L. Hamilton, F. Yesim Demirci, Eric M. Reiman, Charles DeCarli, John M Olichney, Richard Mayeux, Gregory A. Jicha, Michael R. O'Connell, Matt Tector, Eileen H. Bigio, Jonathan D. Glass, M. Ilyas Kamboh, Randall E. Brand, Christopher Lawrence, Steven E. Arnold, Jessica LaRusch, Elaine R. Peskind, David H. Cribbs, M.-Marsel Mesulam, Constantine G. Lyketsos, Michelle L. Kienholz, Frank M. LaFerla, Duane Beekly, Kelley Faber, Salvatore Spina, Gyungah Jun, Thiruvengadam Muniraj, Erik D. Roberson, Anna Karydas, Steven H. Ferris, Bruce L. Miller, Randall L. Woltjer, Li-San Wang, Lon S. Schneider, John C. Morris, John Q. Trojanowski, Jeffrey Kaye, Joseph E. Parisi, Nilufer Ertekin-Taner, Harry V. Vinters, Lidiya Orlichenko, Robert Barber, Chris E. Forsmark, Mary Sano, Bimaljit S. Sandhu, Peter A. Banks, Martin R. Farlow, Bradley T. Hyman, Joseph F. Quinn, Gary W. Beecham, James A. DiSario, Hakon Hakonarson, Daniel C. Marson, Adam C. Naj, Frank Martiniuk, Oscar L. Lopez, Mary E. Money, Julia Mayerle, William Greenhalf, Kathryn Roeder, Adam L. Boxer, Christine M. Hulette, Gerard D. Schellenberg, Georgios I. Papachristou, Douglas Galasko, James R. Burke, Donna B. Stolz, Murray A. Raskind, Peter Simon, Linda J. Van Eldik, Robert A. Hawes, Chang En Yu, Tatiana Foroud, Jonathan L. Haines, Stephen R. Wisniewski, William W. Seeley, Dhiraj Yadav, James J. Lah, C. Mel Wilcox, Sid Gilman, Liana G. Apostolova, Howard J. Rosen, Clinton T. Baldwin, Robert S. Stern, Narcis O. Zarnescu, Dennis W. Dickson, Margaret A. Pericak-Vance, Ashok Raj, Stephen T. Amann, Joseph D. Buxbaum, Ronald C. Petersen, Robert C. Green, David C. Whitcomb, Rudolph E. Tanzi, Lindsay A. Farrer, Helena C. Chui, Laura B. Cantwell, Wendy J. Mack, Samer Alkaade, Nigel J. Cairns, Thomas G. Beach, Frank Ulrich Weiss, Alyssa M. Krasinskas, Elizabeth Head, Nalini M. Guda, Julie A. Schneider, Malcolm B. Dick, Roger N. Rosenberg, Jill R. Murrel, Otto Valladares, Andrew J. Saykin, Huntington Potter, John R. Gilbert, Neil W. Kowall, Joseph Romagnuolo, Markus M. Lerch, Aimee Pierce, Roger L. Albin, John M. Ringman, James B. Leverenz, Carlos Cruchaga, Joshua W. Miller, Lei Yu, M. Michael Barmada, Lambertus Klei, Andrew P. Lieberman, Bernardino Ghetti, Robert Sutton, Kathleen A. Welsh-Bohmer, Juan C. Troncoso, Edward H. Koo, Elizabeth Crocco, Eden R. Martin, Daniel H. Geschwind, and Regina M. Carney
Subjects: Male, Pancreatic disease, Pancreatitis, Alcoholic, Genome-wide association study, Biology, Article, 03 medical and health sciences, 0302 clinical medicine, Sex Factors, Gene Frequency, Genotype, Genetics, medicine, PRSS2, Humans, Genetic Predisposition to Disease, Trypsin, Allele, Allele frequency, Homozygote, Genetic Variation, medicine.disease, 3. Good health, Hemizygote, 030220 oncology & carcinogenesis, Immunology, Claudins, Mutation, Trypsinogen, Pancreatitis, 030211 gastroenterology & hepatology, Female, Genome-Wide Association Study
Abstract: Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR and SPINK1 variants were associated with pancreatitis risk. We now report two associations at genome-wide significance identified and replicated at PRSS1-PRSS2 (P < 1 × 10(-12)) and X-linked CLDN2 (P < 1 × 10(-21)) through a two-stage genome-wide study (stage 1: 676 cases and 4,507 controls; stage 2: 910 cases and 4,170 controls). The PRSS1 variant likely affects disease susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous (or hemizygous in males) CLDN2 genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men (male hemizygote frequency is 0.26, whereas female homozygote frequency is 0.07).
Published: 2012

20. Identification of common variants influencing risk of the tauopathy Progressive Supranuclear Palsy

Author: Marla Gearing, Jean Paul G. Vonsattel, Anna Karydas, Manuela Apfelbacher, Herbert Budka, Bernie Devlin, Alessandro Padovani, Wallace W. Tourtellotte, Andrew J. Lees, Karin Srulijes, Li-San Wang, Klaus Seppi, Gianni Pezzoli, Yvette Bordelon, Claudia Trenkwalder, Ryan J. Uitti, Peter Paul De Deyn, Nicole A. Finch, Roger L. Albin, Ranjan Duara, Gerard D. Schellenberg, Alberto Rábano, Kelly E. Lyons, Rosa Rademakers, Douglas Galasko, Giorgio Sacilotto, Dennis W. Dickson, Günter U. Höglinger, Silvana Tesei, John Hardy, Carlo Colosimo, Eliezer Masliah, Pia Winter, Joseph Jankovic, William W. Seeley, Claudio Mariani, David E. Riley, Matthew J. Farrer, Angelo Antonini, Jens Carsten Möller, Alex Rajput, Hans A. Kretzschmar, Nenad Bogdanovic, Nadine M. Melhem, Ulrich Müller, Steven E. Arnold, Wolfgang H. Oertel, Jorge L. Juncos, Rachel G. Gross, Daniela Berg, Rajesh Pahwa, Deborah A. Hall, Alexandra Durr, Chris Zarow, Lili-Naz Hazrati, Virginia M.-Y. Lee, Justo Garcãa De Yebenes, Donatella Ottaviani, John C. van Swieten, Tamas Revesz, John Q. Trojanowski, Zbigniew K. Wszolek, Sigrun Roeber, Werner Poewe, Matthias Höllerhage, Neill R. Graff-Radford, Laura B. Cantwell, Elena Alonso, Irene Litvan, Claire Troakes, Patrick M. A. Sleiman, Peter St George-Hyslop, Isabelle Leber, Lawrence I. Golbe, Chang En Yu, Allissa Dillman, Anna Zecchinelli, Stephen G. Reich, Stefano Goldwurm, Salvatore Spina, Eduardo Tolosa, Vivianna M. Van Deerlin, Charles L. White, Agnita J.W. Boon, Andrew B. Singleton, Huw R. Morris, Mi Ryung Han, Dena G. Hernandez, Carles Gaig, Matthew P. Frosch, Sebastiaan Engelborghs, Juan C. Troncoso, Roberto Cilia, Catriona McLean, Thomas Gasser, Robyn Flook, Barbara Borroni, Rohan de Silva, Murray Grossman, Martin N. Rossor, Bruce L. Miller, Sean S. O'Sullivan, Hakon Hakonarson, Walter Maetzler, Thomas D. Bird, David G. Standaert, Gesine Respondek, Marcel P. van der Brug, Sherry Beecher, Howard I. Hurtig, Gregor K. Wenning, J. Raphael Gibbs, Alexis Brice, Stuart Pickering-Brown, Jonathan D. Rohrer, Christopher Morris, Jana Vandrovcova, Giovanni Fabbrini, Jesús Avila, Owen A. Ross, Margherita Canesi, Lambertus Klei, Andrew P. Lieberman, Bernardino Ghetti, Laura Silveira-Moriyama, Peter Heutink, Pau Pastor, Nicoletta Meucci, Evan T. Geller, Luke A. Massey, Wang Zheng Chiu, Laura Donker Kaat, Maria Stamelou, Brit Mollenhauer, Mark R. Cookson, Thomas G. Beach, Novartis, Federal Ministry of Education and Research (Germany), Helmholtz Association, European Commission, Human genetics, NCA - Neurodegeneration, Neurology, Foundation for the National Institutes of Health, National Institute of Mental Health (US), German Genomics Initiative, German Research Foundation, Medical Research Council (UK), NIHR Biomedical Research Centre (UK), Harvard Brain Tissue Resource Center, Telethon Italia, Canadian Institutes of Health Research, Mayo Clinic, Nafarroako Gobernua, Fondazione Grigioni per il Morbo di Parkinson, De Deyn, Peter Paul, Engelborghs, Sebastiaan, and PSP Genetics Study Group
Subjects: pathology [Tauopathies], Genome-wide association study, Neurodegenerative, Medical and Health Sciences, Cohort Studies, 0302 clinical medicine, Degenerative disease, Risk Factors, Corticobasal degeneration, GWAS, 2.1 Biological and endogenous factors, Supranuclear Palsy, Chromosomes, Human, EIF2AK3, Aetiology, Genetics, Pediatric, 0303 health sciences, genetics [Supranuclear Palsy, Progressive], Single Nucleotide, Biological Sciences, Prognosis, 3. Good health, Frontotemporal Dementia (FTD), Tauopathies, Neurological, genetics [Polymorphism, Single Nucleotide], Tauopathy, Brain diseases, Supranuclear Palsy, Progressive, Palsy, Human, pathology [Supranuclear Palsy, Progressive], Single-nucleotide polymorphism, MAPT protein, human, tau Proteins, Neuropathology, Progressive Supranuclear Palsy, Biology, genetics [Chromosomes, Human], Polymorphism, Single Nucleotide, Chromosomes, Article, Progressive supranuclear palsy, PSP Genetics Study Group, 03 medical and health sciences, Rare Diseases, Progressive, ddc:570, medicine, Acquired Cognitive Impairment, Humans, Genetic Predisposition to Disease, Polymorphism, 030304 developmental biology, Cerebral Palsy, Prevention, Human Genome, genetics [Tauopathies], Neurosciences, Genetic Variation, Perinatal Period - Conditions Originating in Perinatal Period, medicine.disease, eye diseases, Brain Disorders, genetics [tau Proteins], Genetic Loci, Case-Control Studies, Dementia, Human medicine, 030217 neurology & neurosurgery, Developmental Biology, Genome-Wide Association Study
Abstract: Progressive supranuclear palsy (PSP) is a movement disorder with prominent tau neuropathology. Brain diseases with abnormal tau deposits are called tauopathies, the most common being Alzheimer’s disease. Environmental causes of tauopathies include repetitive head trauma associated with some sports. To identify common genetic variation contributing to risk for tauopathies, we carried out a genome-wide association study of 1,114 PSP cases and 3,247 controls (Stage 1) followed up by a second stage where 1,051 cases and 3,560 controls were genotyped for Stage 1 SNPs that yielded P ≤ 10−3. We found significant novel signals (P < 5 × 10−8) associated with PSP risk at STX6, EIF2AK3, and MOBP. We confirmed two independent variants in MAPT affecting risk for PSP, one of which influences MAPT brain expression. The genes implicated encode proteins for vesicle-membrane fusion at the Golgi-endosomal interface, for the endoplasmic reticulum unfolded protein response, and for a myelin structural component., T.G. serves as an editorial board member of Movement Disorders and Parkinsonism and Related Disorders and is funded by Novartis Pharma, the Federal Ministry of Education and Research (BMBF) (NGFN-Plus and ERA-Net NEURON), the Helmholtz Association (HelMA, Helmholtz Alliance for Health in an Ageing Society) and the European Community (MeFoPa, Medndelian Forms of Parkinsonism). T.G. received speakers honoraria from Novartis, Merck-Serono, Schwarz Pharma, Boehringer Ingelheim and Valeant Pharma and royalties for his consulting activities from Cefalon Pharma and Merck-Serono. T.G. holds a patent concerning the LRRK2 gene and neurodegenerative disorders. J.H. is consulting for Merck Serono and Eisai. I.Litvan is the founder of the Litvan Neurological Research Foundation, whose mission is to increase awareness, determine the cause/s and search for a cure for neurodegenerative disorders presenting with either parkinsonian or dementia symptoms (501c3).
Published: 2011
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21. Common variants in MS4A4/MS4A6E, CD2uAP, CD33, and EPHA1 are associated with late-onset Alzheimer’s disease

Author: Bradley T. Hyman, Tatiana Foroud, James J. Lah, Roger N. Rosenberg, Philip L. De Jager, John M. Ringman, Thomas D. Bird, Ramon Diaz-Arrastia, Wayne W. Poon, Barry Reisberg, Juan C. Troncoso, Peter St George-Hyslop, Deborah Blacker, Ronald C. Kim, Adam L. Boxer, Gerard D. Schellenberg, Douglas Galasko, John Hardy, Erik D. Roberson, Minerva M. Carrasquillo, Richard Mayeux, Steven L. Carroll, Elaine R. Peskind, Walter A. Kukull, Marla Gearing, Lee-Way Jin, Paul K. Crane, James D. Bowen, Deborah C. Mash, Carol A. Miller, Eileen H. Bigio, Duane Beekly, Kenneth B. Fallon, Bruce L. Miller, Eliezer Masliah, Charles DeCarli, Gyungah Jun, Mary Ganguli, M. Ilyas Kamboh, Steven E. Arnold, Patricia L. Kramer, Gregory A. Jicha, David G. Clark, Lon S. Schneider, William G. Ellis, Anna Karydas, Alison Goate, Michael A. Slifer, Matthew P. Frosch, Steven G. Younkin, Steven T. DeKosky, F. Yesim Demirci, John Q. Trojanowski, Jeffrey Kaye, Sandra Weintraub, Jonathan D. Glass, Lindy E. Harrell, Adam C. Naj, Frank Martiniuk, Harry V. Vinters, Gail P. Jarvik, Ronald L. Hamilton, Ruchita Rajbhandary, Wayne C. McCormick, Neill R. Graff-Radford, Allan I. Levey, Jennifer Williamson, Daniel C. Marson, Andrew McDavid, John R. Gilbert, Thomas H. Beach, Christine M. Hulette, David A. Bennett, William P. Seeley, Christopher S. Carlson, Amanda J. Myers, Hakon Hakonarson, Debby W. Tsuang, Kathryn L. Lunetta, James R. Burke, Sid Gilman, John C. Morris, Bradley F. Boeve, Oscar L. Lopez, Nilufer Ertekin-Taner, Thomas J. Montine, Daniel P. Perl, Eric M. Reiman, Joseph F. Quinn, Susan M. McCurry, Paul Gallins, Murray A. Raskind, Badri N. Vardarajan, Joshua A. Sonnen, Robert S. Stern, Denis A. Evans, Lawrence S. Honig, Ekaterina Rogaeva, John H. Growdon, Michael L. Shelanski, Vivianna M. Van Deerlin, Joseph E. Parisi, Mary Sano, Dennis W. Dickson, Steven H. Ferris, Randall L. Woltjer, Li-San Wang, Jonathan L. Haines, Bruno Giordani, Martin R. Farlow, Jason J. Corneveaux, Gary W. Beecham, Clinton T. Baldwin, Ann C. McKee, Jean Paul Vonsattel, Julie A. Schneider, Malcolm B. Dick, Kelley Faber, John S. K. Kauwe, Neil W. Kowall, Wendy J. Mack, W Marsel Mesulam, Nigel J. Cairns, Nancy Johnson, Jacqueline L. Buros, Eric B. Larson, Ronald C. Petersen, Laura B. Cantwell, Margaret A. Pericak-Vance, Elizabeth Head, Petra Nowotny, Joseph D. Buxbaum, Andrew J. Saykin, Robert C. Green, Lindsay A. Farrer, Carlos Cruchaga, Joshua W. Miller, Matthew J. Huentelman, Rudolph E. Tanzi, Beth A. Dombroski, Andrew P. Lieberman, Daniel H. Geschwind, Robert W Barber, Jeffrey L. Cummings, Charles D. Smith, Bernardino Ghetti, Salvatore Spina, Regina M. Carney, Kathleen A. Welsh-Bohmer, Jason Karlawish, Edward H. Koo, Eden R. Martin, M. Michael Barmada, Carl W. Cotman, and Helena C. Chui
Subjects: Male, Sialic Acid Binding Ig-like Lectin 3, Antigens, Differentiation, Myelomonocytic, Late onset, Joint analysis, Biology, Polymorphism, Single Nucleotide, Article, Cohort Studies, 03 medical and health sciences, Disease susceptibility, 0302 clinical medicine, Alzheimer Disease, Antigens, CD, Databases, Genetic, Genetics, Humans, Genetic Predisposition to Disease, Age of Onset, 030304 developmental biology, Adaptor Proteins, Signal Transducing, Aged, Aged, 80 and over, 0303 health sciences, Receptor, EphA1, Genetic Variation, Membrane Proteins, Molecular biology, 3. Good health, Cytoskeletal Proteins, Multigene Family, Female, 030217 neurology & neurosurgery, Genome-Wide Association Study
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

22. Association of Long Runs of Homozygosity With Alzheimer Disease Among African American Individuals

Author: Lee-Way Jin, Rudolph E. Tanzi, Lisa L. Barnes, Neill R. Graff-Radford, Joel H. Kramer, Tatiana Foroud, John R. Gilbert, Wayne W. Poon, Philip L. De Jager, Lei Yu, John M. Ringman, James J. Lah, Marla Gearing, David A. Bennett, Susan M. McCurry, Kenneth B. Fallon, Clinton B. Wright, Deborah Blacker, Bradley T. Hyman, Patricia L. Kramer, Joseph F. Quinn, Alison Goate, Gail P. Jarvik, Allan I. Levey, Jennifer Williamson, Mary Ganguli, Carlos Cruchaga, Julie A. Schneider, Amanda Smith, Eric M. Reiman, Lon S. Schneider, Steven H. Ferris, Richard Mayeux, Randall L. Woltjer, Li-San Wang, Goldie S. Byrd, Malcolm B. Dick, Towfique Raj, Steven L. Carroll, Carol A. Miller, Bradley F. Boeve, John S. K. Kauwe, Elaine R. Peskind, Hugh C. Hendrie, R. C. Kim, Jonathan D. Glass, Helena C. Chui, Guiqing Cai, Deborah C. Mash, Gyungah Jun, James Bowen, Marilyn S. Albert, Kathryn L. Lunetta, Huntington Potter, Walter A. Kukull, Paul K. Crane, Neil W. Kowall, Mark W. Logue, Lindsay A. Farrer, Jean Paul G. Vonsattel, Chang-En Yu, Thomas G. Beach, Gary W. Beecham, Erik D. Roberson, John M Olichney, Gerard D. Schellenberg, Harry V. Vinters, Chiao-Feng Lin, Bruce L. Miller, Duane Beekly, Daniel H. Geschwind, Murray A. Raskind, Kara L. Hamilton-Nelson, Jill R. Murrell, Linda J. Van Eldik, Wendy J. Mack, A. Karydas, Douglas Galasko, Barry Reisberg, Thomas O. Obisesan, Aimee Pierce, Andrew McDavid, Salvatore Spina, M.-Marsel Mesulam, Steven T. DeKosky, Andrew P. Lieberman, Ann C. McKee, Robert Barber, Nigel J. Cairns, Roger L. Albin, Bernardino Ghetti, Nilufer Ertekin-Taner, Kathleen A. Welsh-Bohmer, James B. Leverenz, M. Michael Barmada, F. Yesim Demirci, Hakon Hakonarson, Rodney C.P. Go, Oscar L. Lopez, Joseph D. Buxbaum, Adam C. Naj, Frank Martiniuk, Charles DeCarli, Otto Valladares, Andrew J. Saykin, Kelley Faber, Christine M. Hulette, John C. Morris, M. Ilyas Kamboh, Eliezer Masliah, Christine Sato, Steven E. Arnold, James R. Burke, Daniel C. Marson, Edward H. Koo, Ronald C. Petersen, David G. Clark, William W. Seeley, Robert C. Green, Constantine G. Lyketsos, Rosalyn Lang-Walker, John Q. Trojanowski, Jeffrey Kaye, Eileen H. Bigio, Laura B. Cantwell, Matthew P. Frosch, Jonathan L. Haines, Debby W. Tsuang, Juan C. Troncoso, Joshua W. Miller, Denis A. Evans, Kathleen S. Hall, Frank M. LaFerla, Joseph E. Parisi, Elizabeth Crocco, Mary Sano, Mahdi Ghani, Patrick Griffith, Margaret A. Pericak-Vance, Ashok Raj, Christopher S. Carlson, Jennifer J. Manly, Sid Gilman, Thomas J. Montine, Chuanhai Cao, A. Boxer, Ekaterina Rogaeva, Steven G. Younkin, Ronald L. Hamilton, Rong Cheng, Vahram Haroutunian, Peter St George-Hyslop, Liana G. Apostolova, M. Daniele Fallin, Clinton T. Baldwin, Ruchita Rajbhandary, Robert S. Stern, Sandra Weintraub, David H. Cribbs, Lindy E. Harrell, Wayne C. McCormick, Ge Li, Christiane Reitz, Eric B. Larson, Thomas D. Bird, Gregory A. Jicha, Regina M. Carney, Badri N. Vardarajan, Joshua A. Sonnen, Lawrence S. Honig, Joseph H. Lee, John H. Growdon, and Vivianna M. Van Deerlin
Subjects: Genetics, Chicago, Indiana, business.industry, Haplotype, Homozygote, Case-control study, Single-nucleotide polymorphism, Genome-wide association study, Genes, Recessive, Runs of Homozygosity, Polymorphism, Single Nucleotide, Article, Black or African American, Alzheimer Disease, Case-Control Studies, SNP, Medicine, Humans, Neurology (clinical), business, Imputation (genetics), SNP array, Aged, Genome-Wide Association Study
Abstract: Importance Mutations in known causal Alzheimer disease (AD) genes account for only 1% to 3% of patients and almost all are dominantly inherited. Recessive inheritance of complex phenotypes can be linked to long (>1-megabase [Mb]) runs of homozygosity (ROHs) detectable by single-nucleotide polymorphism (SNP) arrays. Objective To evaluate the association between ROHs and AD in an African American population known to have a risk for AD up to 3 times higher than white individuals. Design, Setting, and Participants Case-control study of a large African American data set previously genotyped on different genome-wide SNP arrays conducted from December 2013 to January 2015. Global and locus-based ROH measurements were analyzed using raw or imputed genotype data. We studied the raw genotypes from 2 case-control subsets grouped based on SNP array: Alzheimer’s Disease Genetics Consortium data set (871 cases and 1620 control individuals) and Chicago Health and Aging Project–Indianapolis Ibadan Dementia Study data set (279 cases and 1367 control individuals). We then examined the entire data set using imputed genotypes from 1917 cases and 3858 control individuals. Main Outcomes and Measures The ROHs larger than 1 Mb, 2 Mb, or 3 Mb were investigated separately for global burden evaluation, consensus regions, and gene-based analyses. Results The African American cohort had a low degree of inbreeding ( F ~ 0.006). In the Alzheimer’s Disease Genetics Consortium data set, we detected a significantly higher proportion of cases with ROHs greater than 2 Mb ( P = .004) or greater than 3 Mb ( P = .02), as well as a significant 114-kilobase consensus region on chr4q31.3 (empirical P value 2 = .04; ROHs >2 Mb). In the Chicago Health and Aging Project–Indianapolis Ibadan Dementia Study data set, we identified a significant 202-kilobase consensus region on Chr15q24.1 (empirical P value 2 = .02; ROHs >1 Mb) and a cluster of 13 significant genes on Chr3p21.31 (empirical P value 2 = .03; ROHs >3 Mb). A total of 43 of 49 nominally significant genes common for both data sets also mapped to Chr3p21.31. Analyses of imputed SNP data from the entire data set confirmed the association of AD with global ROH measurements (12.38 ROHs >1 Mb in cases vs 12.11 in controls; 2.986 Mb average size of ROHs >2 Mb in cases vs 2.889 Mb in controls; and 22% of cases with ROHs >3 Mb vs 19% of controls) and a gene-cluster on Chr3p21.31 (empirical P value 2 = .006-.04; ROHs >3 Mb). Also, we detected a significant association between AD and CLDN17 (empirical P value 2 = .01; ROHs >1 Mb), encoding a protein from the Claudin family, members of which were previously suggested as AD biomarkers. Conclusions and Relevance To our knowledge, we discovered the first evidence of increased burden of ROHs among patients with AD from an outbred African American population, which could reflect either the cumulative effect of multiple ROHs to AD or the contribution of specific loci harboring recessive mutations and risk haplotypes in a subset of patients. Sequencing is required to uncover AD variants in these individuals.
Published: 2015

23. O3‐05‐03: Multiple deletion copy number variants (CNVs) are associated with late‐onset Alzheimer's disease: The Alzheimer's disease genetics consortium

Author: Chiao-Feng Lin, Weixin Wang, Otto Valladares, Adam C. Naj, Li-San Wang, Laura B. Cantwell, Gerard D. Schellenberg, and Amanda Partch
Subjects: Genetics, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Multiple deletion, Late onset, Neurology (clinical), Copy-number variation, Disease, Geriatrics and Gerontology, Biology
Published: 2015
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24. Genome-wide association study of corticobasal degeneration identifies risk variants shared with progressive supranuclear palsy

Author: Gerard D. Schellenberg, Owen A. Ross, Rosa Rademakers, Matthew C. Baker, Laura B. Cantwell, Lawrence I. Golbe, Salvatore Spina, Beth A. Dombroski, Hyejin Yoon, Hakon Hakonarsen, Mi Ryung Han, Jorge L. Juncos, Bernardino Ghetti, Günter U. Höglinger, Daniel J. Serie, Alexandra I. Soto-Ortolaza, Marla Gearing, Curtis S. Younkin, John Q. Trojanowski, Zbigniew K. Wszolek, Jungsu Kim, Evan T. Geller, Bernie Devlin, Howard I. Hurtig, Sherry Beecher, Naomi Kouri, Rachel Goldmann Gross, Steven E. Arnold, Gregor K. Wenning, Keith A. Josephs, Nilufer Ertekin-Taner, Ulrich Müller, Bradley F. Boeve, Shinsuke Fujioka, Virginia M.-Y. Lee, Murray Grossman, Joseph E. Parisi, Steven G. Younkin, Ni Cole A. Finch, Jordan Grafman, Edward D. Huey, Charles L. White, Irene Litvan, Catriona McLean, Vivianna M. Van Deerlin, Neill R. Graff-Radford, Dennis W. Dickson, Julia E. Crook, Hans A. Kretzschmar, Sigrun Roeber, Jean Paul Vonsattel, Li-San Wang, Ryan J. Uitti, and Martin R. Farlow
Subjects: Male, genetics [Basal Ganglia Diseases], genetics [Kinesin], genetics [SOS1 Protein], Kinesins, General Physics and Astronomy, Genome-wide association study, genetics [RNA, Long Noncoding], Polymorphism (computer science), Corticobasal degeneration, Basal ganglia disease, Genetics, Aged, 80 and over, Cerebral Cortex, Multidisciplinary, KIF13B protein, human, genetics [Supranuclear Palsy, Progressive], Neurodegenerative Diseases, Kinesin, Middle Aged, ddc, 3. Good health, Female, RNA, Long Noncoding, Supranuclear Palsy, Progressive, ddc:500, SOS1 Protein, Engineering sciences. Technology, Myelin Proteins, Adult, genetics [Kinesins], Single-nucleotide polymorphism, MAPT protein, human, tau Proteins, Biology, Polymorphism, Single Nucleotide, Article, General Biochemistry, Genetics and Molecular Biology, genetics [Myelin Proteins], Progressive supranuclear palsy, Young Adult, Basal Ganglia Diseases, medicine, SNP, Humans, Aged, Case-control study, General Chemistry, medicine.disease, genetics [tau Proteins], Case-Control Studies, genetics [Neurodegenerative Diseases], MOBP protein, human, Genome-Wide Association Study
Abstract: Corticobasal degeneration (CBD) is a neurodegenerative disorder affecting movement and cognition, definitively diagnosed only at autopsy. Here, we conduct a genome-wide association study (GWAS) in CBD cases (n=152) and 3,311 controls, and 67 CBD cases and 439 controls in a replication stage. Associations with meta-analysis were 17q21 at MAPT (P=1.42 × 10−12), 8p12 at lnc-KIF13B-1, a long non-coding RNA (rs643472; P=3.41 × 10−8), and 2p22 at SOS1 (rs963731; P=1.76 × 10−7). Testing for association of CBD with top progressive supranuclear palsy (PSP) GWAS single-nucleotide polymorphisms (SNPs) identified associations at MOBP (3p22; rs1768208; P=2.07 × 10−7) and MAPT H1c (17q21; rs242557; P=7.91 × 10−6). We previously reported SNP/transcript level associations with rs8070723/MAPT, rs242557/MAPT, and rs1768208/MOBP and herein identified association with rs963731/SOS1. We identify new CBD susceptibility loci and show that CBD and PSP share a genetic risk factor other than MAPT at 3p22 MOBP (myelin-associated oligodendrocyte basic protein)., Corticobasal degeneration is a rare neurodegenerative disorder that can only be definitively diagnosed by autopsy. Here, Kouri et al. conduct a genome-wide-association study and identify two genetic susceptibility loci 17q21 (MAPT) and 3p12 (MOBP), and a novel susceptibility locus at 8p12.
Published: 2015
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25. Global and local ancestry in African-Americans: Implications for Alzheimer's disease risk

Author: Gerard D. Schellenberg, John Hardy, Rodney C.P. Go, Oscar L. Lopez, Richard Mayeux, Jonathan L. Haines, Denis A. Evans, Nilufer Ertekin-Taner, Lindsay A. Farrer, Philip L. De Jager, Walter A. Kukull, Eden R. Martin, Chiao-Feng Lin, Towfique Raj, Laura B. Cantwell, Alison Goate, Rosalyn Lang, Goldie S. Byrd, Mark W. Logue, Tatiana Foroud, Tricia A. Thornton-Wells, Neill R. Graff-Radford, Jeffrey M. Vance, M. Daniele Fallin, Patrick Griffith, Clinton T. Baldwin, Lisa L. Barnes, Margaret A. Pericak-Vance, Paul K. Crane, Adam C. Naj, Ruchita Rajbhandary, Badri N. Vardarajan, Zhi Liu, Joseph D. Buxbaum, Jill R. Murrell, Kathleen S. Hall, Michael L. Cuccaro, Robert C. Green, Thomas O. Obisesan, Timothy J. Hohman, Otto Valladares, Kathryn L. Lunetta, Li-San Wang, Gary W. Beecham, David A. Bennett, Gyungah Jun, Jennifer J. Manly, Christiane Reitz, Eric B. Larson, Regina M. Carney, M. Ilyas Kamboh, Jessica N. Cooke-Bailey, and Hugh C. Hendrie
Subjects: 0301 basic medicine, Gerontology, Apolipoprotein E, Male, Genotype, Epidemiology, Sialic Acid Binding Ig-like Lectin 3, Genetic admixture, Genome-wide association study, Disease, Polymorphism, Single Nucleotide, Article, Cohort Studies, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Apolipoproteins E, Developmental Neuroscience, Alzheimer Disease, Medicine, Humans, Genetic Predisposition to Disease, Genetic Association Studies, Aged, Aged, 80 and over, Chromosome Aberrations, Chi-Square Distribution, business.industry, Health Policy, medicine.disease, Black or African American, Psychiatry and Mental health, 030104 developmental biology, ATP-Binding Cassette Transporters, Female, Neurology (clinical), Geriatrics and Gerontology, Alzheimer's disease, business, Chi-squared distribution, 030217 neurology & neurosurgery, Demography, Cohort study
Abstract: Introduction African-American (AA) individuals have a higher risk for late-onset Alzheimer's disease (LOAD) than Americans of primarily European ancestry (EA). Recently, the largest genome-wide association study in AAs to date confirmed that six of the Alzheimer's disease (AD)-related genetic variants originally discovered in EA cohorts are also risk variants in AA; however, the risk attributable to many of the loci (e.g., APOE, ABCA7) differed substantially from previous studies in EA. There likely are risk variants of higher frequency in AAs that have not been discovered. Methods We performed a comprehensive analysis of genetically determined local and global ancestry in AAs with regard to LOAD status. Results Compared to controls, LOAD cases showed higher levels of African ancestry, both globally and at several LOAD relevant loci, which explained risk for AD beyond global differences. Discussion Exploratory post hoc analyses highlight regions with greatest differences in ancestry as potential candidate regions for future genetic analyses.
Published: 2014

26. P1–063: Association of TREM2 variants with Alzheimer's disease in African‐Americans: For the Alzheimer's Disease Genetics Consortium (ADGC)

Author: Jennifer J. Manly, Mark W. Logue, Alison Goate, Walter A. Kukull, Robert Green, Gerard D. Schellenberg, Goldie S. Byrd, Laura B. Cantwell, Eric B. Larson, David A. Bennett, Kathryn L. Lunetta, Philip L. De Jager, Jonathan L. Haines, Neill R. Graff-Radford, Denis A. Evans, Lindsay A. Farrer, Li-San Wang, Richard Mayeux, Badri N. Vardarajan, Joseph D. Buxbaum, Nilufer Ertekin-Taner, Tatiana Foroud, Oscar L. Lopez, Adam C. Naj, Gyungah Jun, Margaret A. Pericak-Vance, Christiane Reitz, Paul K. Crane, Kathleen S. Hall, Ilyas Kamboh, and Danielle Fallin
Subjects: Genetics, medicine.medical_specialty, History, Epidemiology, Health Policy, Public health, Columbia university, Human genomics, Miami, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, medicine, University medical, Neurology (clinical), Geriatrics and Gerontology
Abstract: P1-063 ASSOCIATION OF TREM2 VARIANTS WITH ALZHEIMER’S DISEASE IN AFRICANAMERICANS: FOR THE ALZHEIMER’S DISEASE GENETICS CONSORTIUM (ADGC) Christiane Reitz, Gyungah Jun, Adam Naj, Badri Vardarajan, Li-SanWang, Eric Larson, Neill Graff-Radford, Denis Evans, Philip De Jager, Paul Crane, Joseph Buxbaum, Nilufer Ertekin-Taner, Mark Logue, Robert Green, Laura Cantwell, Danielle Fallin, Jennifer Manly, Kathryn Lunetta, Ilyas Kamboh, Oscar Lopez, David Bennett, Kathleen Steele Hall, Alison Goate, Goldie Byrd, Walter Kukull, Tatiana Foroud, Jonathan Haines, Lindsay Farrer, Margaret Pericak-Vance, Gerard Schellenberg, Richard Mayeux, Columbia University, New York, New York, United States; Boston University School of Medicine, Boston, Massachusetts, United States; University of Miami Hussman Institute for Human Genomics, Miami, Florida, United States; Columbia University, Boston, Massachusetts, United States; University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States; Group Health Research Institute, Seattle, Washington, United States; Mayo Clinic Jacksonville, Jacksonville, Florida, United States; Rush University Medical Center, Chicago, Illinois, United States; Brigham & Women’s Hospital, Boston, Massachusetts, United States; Mt. Sinai Hospital, New York, New York, United States; Mayo, Jacksonville, Florida, United States; Boston University School of Medicine/Biomedical Genetics, Boston, Massachusetts, United States; University of Pittsburgh Schools of Nursing and Medicine, Pittsburgh, Pennsylvania, United States; University of Pennsylvania, Philadelphia, Pennsylvania, United States; Johns Hopkins University, Baltimore, Maryland, United States; Columbia University Medical Center, New York, New York, United States; Boston University School of Public Health, Boston,Massachusetts, United States; University of Pittsburgh, Pittsburgh, Pennsylvania, United States; University of Pittsburgh, Pittsburgh, Pennsylvania, United States; Rush University Medical Center, Chicago, Illinois, United States; Indiana University, Indianapolis, Indiana, United States; Washington University, St. Louis, Saint Louis, Missouri, United States; North Carolina AT National Alzheimer’s Coordinating Center, Seattle, Washington, United States; Indiana University School of Medicine, Indianapolis, Indiana, United States; Vanderbilt University, Nashville, Tennessee, United States; Boston University, Boston, Massachusetts, United States; Vanderbilt University, Nashville, Tennessee, United States; University of Pennsylvania, Philadelphia, Pennsylvania, United States. Contact e-mail: cr2101@columbia.edu
Published: 2013
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27. Assessment of the genetic variance of late-onset Alzheimer's disease

Author: Perry G. Ridge, Kaitlyn B. Hoyt, Kevin Boehme, Shubhabrata Mukherjee, Paul K. Crane, Jonathan L. Haines, Richard Mayeux, Lindsay A. Farrer, Margaret A. Pericak-Vance, Gerard D. Schellenberg, John S.K. Kauwe, Perrie M. Adams, Marilyn S. Albert, Roger L. Albin, Liana G. Apostolova, Steven E. Arnold, Sanjay Asthana, Craig S. Atwood, Clinton T. Baldwin, Robert C. Barber, Michael M. Barmada, Lisa L. Barnes, Sandra Barral, Thomas G. Beach, James T. Becker, Gary W. Beecham, Duane Beekly, David A. Bennett, Eileen H. Bigio, Thomas D. Bird, Deborah Blacker, Bradley F. Boeve, James D. Bowen, Adam Boxer, James R. Burke, Jeffrey M. Burns, Joseph D. Buxbaum, Nigel J. Cairns, Laura B. Cantwell, Chuanhai Cao, Chris S. Carlson, Cynthia M. Carlsson, Regina M. Carney, Minerva M. Carrasquillo, Steven L. Carroll, Helena C. Chui, David G. Clark, Jason Corneveaux, David H. Cribbs, Elizabeth A. Crocco, Carlos Cruchaga, Philip L. De Jager, Charles DeCarli, F. Yesim Demirci, Malcolm Dick, Dennis W. Dickson, Rachelle S. Doody, Ranjan Duara, Nilufer Ertekin-Taner, Denis A. Evans, Kelley M. Faber, Thomas J. Fairchild, Kenneth B. Fallon, David W. Fardo, Martin R. Farlow, Steven Ferris, Tatiana M. Foroud, Matthew P. Frosch, Douglas R. Galasko, Marla Gearing, Daniel H. Geschwind, Bernardino Ghetti, John R. Gilbert, Alison M. Goate, Neill R. Graff-Radford, Robert C. Green, John H. Growdon, Hakon Hakonarson, Ronald L. Hamilton, Kara L. Hamilton-Nelson, John Hardy, Lindy E. Harrell, Lawrence S. Honig, Ryan M. Huebinger, Matthew J. Huentelman, Christine M. Hulette, Bradley T. Hyman, Gail P. Jarvik, Gregory A. Jicha, Lee-Way Jin, Gyungah Jun, M. Ilyas Kamboh, Anna Karydas, Mindy J. Katz, Jeffrey A. Kaye, Ronald Kim, Neil W. Kowall, Joel H. Kramer, Walter A. Kukull, Brian W. Kunkle, Frank M. LaFerla, James J. Lah, Eric B. Larson, James B. Leverenz, Allan I. Levey, Ge Li, Andrew P. Lieberman, Chiao-Feng Lin, Richard B. Lipton, Oscar L. Lopez, Kathryn L. Lunetta, Constantine G. Lyketsos, Wendy J. Mack, Daniel C. Marson, Eden R. Martin, Frank Martiniuk, Deborah C. Mash, Eliezer Masliah, Wayne C. McCormick, Susan M. McCurry, Andrew N. McDavid, Ann C. McKee, Marsel Mesulam, Bruce L. Miller, Carol A. Miller, Joshua W. Miller, Thomas J. Montine, John C. Morris, Jill R. Murrell, Amanda J. Myers, Adam C. Naj, Sid O'Bryant, John M. Olichney, Vernon S. Pankratz, Joseph E. Parisi, Amanda Partch, Henry L. Paulson, William Perry, Elaine Peskind, Ronald C. Petersen, Aimee Pierce, Wayne W. Poon, Huntington Potter, Joseph F. Quinn, Ashok Raj, Murray Raskind, Eric M. Reiman, Barry Reisberg, Joan S. Reisch, Christiane Reitz, John M. Ringman, Erik D. Roberson, Ekaterina Rogaeva, Howard J. Rosen, Roger N. Rosenberg, Donald R. Royall, Mark A. Sager, Mary Sano, Andrew J. Saykin, Julie A. Schneider, Lon S. Schneider, William W. Seeley, Amanda G. Smith, Joshua A. Sonnen, Salvatore Spina, Peter St George-Hyslop, Robert A. Stern, Russell H. Swerdlow, Rudolph E. Tanzi, Tricia A. Thornton-Wells, John Q. Trojanowski, Juan C. Troncoso, Debby W. Tsuang, Otto Valladares, Vivianna M. Van Deerlin, Linda J. Van Eldik, Badri N. Vardarajan, Harry V. Vinters, Jean Paul Vonsattel, Li-San Wang, Sandra Weintraub, Kathleen A. Welsh-Bohmer, Jens R. Wendland, Kirk C. Wilhelmsen, Jennifer Williamson, Thomas S. Wingo, Ashley R. Winslow, Sarah Wishnek, Randall L. Woltjer, Clinton B. Wright, Chuang-Kuo Wu, Steven G. Younkin, Chang-En Yu, and Lei Yu
Subjects: 0301 basic medicine, Male, Risk, Aging, Neuroscience(all), Clinical Neurology, Datasets as Topic, Genome-wide association study, Single-nucleotide polymorphism, Receptors, Cell Surface, Biology, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, Amyloid beta-Protein Precursor, 0302 clinical medicine, Alzheimer Disease, Genetic variation, medicine, Genetics, Humans, Allele, Receptors, Immunologic, Genetic variance, Aged, Aged, 80 and over, Membrane Glycoproteins, TREM2, General Neuroscience, Genetic disorder, Genetic Variation, Alzheimer's disease, Explained variation, medicine.disease, Genetic architecture, 3. Good health, Ageing, 030104 developmental biology, Female, Neurology (clinical), Geriatrics and Gerontology, Netrin Receptors, 030217 neurology & neurosurgery, Genome-Wide Association Study, Developmental Biology
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
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28. P4‐116: The NIA Genetics of Alzheimer's Disease Data Storage Site (NIAGADS)

Author: Li-San Wang, Chiao-Feng Lin, Tatiana Foroud, Gerard D. Schellenberg, Otto Valladares, and Laura B. Cantwell
Subjects: Genetics, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Disease, Geriatrics and Gerontology, Biology
Published: 2012
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29. Novel late-onset Alzheimer disease loci variants associate with brain gene expression

Author: Mariet, Allen, Fanggeng, Zou, High Seng, Chai, Curtis S, Younkin, Julia, Crook, V Shane, Pankratz, Minerva M, Carrasquillo, Christopher N, Rowley, Asha A, Nair, Sumit, Middha, Sooraj, Maharjan, Thuy, Nguyen, Li, Ma, Kimberly G, Malphrus, Ryan, Palusak, Sarah, Lincoln, Gina, Bisceglio, Constantin, Georgescu, Debra, Schultz, Fariborz, Rakhshan, Christopher P, Kolbert, Jin, Jen, Jonathan L, Haines, Richard, Mayeux, Margaret A, Pericak-Vance, Lindsay A, Farrer, Gerard D, Schellenberg, Ronald C, Petersen, Neill R, Graff-Radford, Dennis W, Dickson, Steven G, Younkin, Nilüfer, Ertekin-Taner, Liana G, Apostolova, Steven E, Arnold, Clinton T, Baldwin, Robert, Barber, Michael M, Barmada, Thomas, Beach, Gary W, Beecham, Duane, Beekly, David A, Bennett, Eileen H, Bigio, Thomas D, Bird, Deborah, Blacker, Bradley F, Boeve, James D, Bowen, Adam, Boxer, James R, Burke, Jacqueline, Buros, Joseph D, Buxbaum, Nigel J, Cairns, Laura B, Cantwell, Chuanhai, Cao, Chris S, Carlson, Regina M, Carney, Steven L, Carroll, Helena C, Chui, David G, Clark, Jason, Corneveaux, Carl W, Cotman, Paul K, Crane, Carlos, Cruchaga, Jeffrey L, Cummings, Philip L, De Jager, Charles, DeCarli, Steven T, DeKosky, F Yesim, Demirci, Ramon, Diaz-Arrastia, Malcolm, Dick, Beth A, Dombroski, Ranjan, Duara, William D, Ellis, Denis, Evans, Kelley M, Faber, Kenneth B, Fallon, Martin R, Farlow, Steven, Ferris, Tatiana M, Foroud, Matthew, Frosch, Douglas R, Galasko, Paul J, Gallins, Mary, Ganguli, Marla, Gearing, Daniel H, Geschwind, Bernardino, Ghetti, John R, Gilbert, Sid, Gilman, Bruno, Giordani, Jonathan D, Glass, Alison M, Goate, Robert C, Green, John H, Growdon, Hakon, Hakonarson, Ronald L, Hamilton, John, Hardy, Lindy E, Harrell, Elizabeth, Head, Lawrence S, Honig, Matthew J, Huentelman, Christine M, Hulette, Bradley T, Hyman, Gail P, Jarvik, Gregory A, Jicha, Lee-Way, Jin, Gyungah, Jun, M Ilyas, Kamboh, Jason, Karlawish, Anna, Karydas, John S K, Kauwe, Jeffrey A, Kaye, Nancy, Kennedy, Ronald, Kim, Edward H, Koo, Neil W, Kowall, Patricia, Kramer, Walter A, Kukull, James J, Lah, Eric B, Larson, Allan I, Levey, Andrew P, Lieberman, Oscar L, Lopez, Kathryn L, Lunetta, Wendy J, Mack, Daniel C, Marson, Eden R, Martin, Frank, Martiniuk, Deborah C, Mash, Eliezer, Masliah, Wayne C, McCormick, Susan M, McCurry, Andrew N, McDavid, Ann C, McKee, Marsel, Mesulam, Bruce L, Miller, Carol A, Miller, Joshua W, Miller, Thomas J, Montine, John C, Morris, Amanda J, Myers, Adam C, Naj, Petra, Nowotny, Joseph E, Parisi, Daniel P, Perl, Elaine, Peskind, Wayne W, Poon, Huntington, Potter, Joseph F, Quinn, Ashok, Raj, Ruchita A, Rajbhandary, Murray, Raskind, Eric M, Reiman, Barry, Reisberg, Christiane, Reitz, John M, Ringman, Erik D, Roberson, Ekaterina, Rogaeva, Roger N, Rosenberg, Mary, Sano, Andrew J, Saykin, Julie A, Schneider, Lon S, Schneider, William, Seeley, Michael L, Shelanski, Michael A, Slifer, Charles D, Smith, Joshua A, Sonnen, Salvatore, Spina, Peter, St George-Hyslop, Robert A, Stern, Rudolph E, Tanzi, John Q, Trojanowski, Juan C, Troncoso, Debby W, Tsuang, Vivianna M, Van Deerlin, Badri Narayan, Vardarajan, Harry V, Vinters, Jean Paul, Vonsattel, Li-San, Wang, Sandra, Weintraub, Kathleen A, Welsh-Bohmer, Jennifer, Williamson, and Randall L, Woltjer
Subjects: Male, Candidate gene, Genotype, Apolipoprotein E4, Gene Dosage, Gene Expression, Single-nucleotide polymorphism, Genome-wide association study, Locus (genetics), Biology, Gene dosage, Polymorphism, Single Nucleotide, PICALM, Alzheimer Disease, Risk Factors, Humans, Genetic Predisposition to Disease, Alleles, Genetic association, Aged, Temporal cortex, Genetics, Brain Chemistry, Temporal Lobe, Linear Models, RNA, Female, Neurology (clinical), Autopsy
Abstract: Objective: Recent 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. Methods: We 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. Results: CLU 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 ). Conclusions: CLU 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

30. Evidence for a role of the rare p.A152T variant in MAPT in increasing the risk for FTD-spectrum and Alzheimer's diseases

Author: Jason Lee, Ranjan Duara, Michael A. Slifer, Kenneth B. Fallon, Thomas J. Montine, Beth A. Dombroski, Peter St George-Hyslop, Debby W. Tsuang, Patricia L. Kramer, Duane Beekly, Ronald C. Petersen, Carl W. Cotman, Helena C. Chui, Alison Goate, Michelle K. Lupton, Sid Gilman, Thomas G. Beach, A. Karydas, Andrew McDavid, Susan M. McCurry, William G. Ellis, Bradley T. Hyman, Badri N. Vardarajan, Joshua A. Sonnen, Neill R. Graff-Radford, Robert Barber, Elisavet Preza, Paul Gallins, Lawrence S. Honig, Adam C. Naj, Frank Martiniuk, Jacek Biernat, Christopher S. Carlson, Richard J. Caselli, Huntington Potter, Chris Zarow, Christine M. Hulette, Hakon Hakonarson, Oscar L. Lopez, Alexandra I. Soto-Ortolaza, Eric Klein, Margaret A. Pericak-Vance, Ashok Raj, Marla Gearing, Kathryn L. Lunetta, Adam L. Boxer, Gerard D. Schellenberg, John H. Growdon, Ramon Diaz-Arrastia, Wayne W. Poon, James R. Burke, Michael D. Geschwind, Douglas Galasko, Ruchita Rajbhandary, Eric M. Reiman, Gregory A. Jicha, Steven L. Carroll, Robert S. Stern, Vivianna M. Van Deerlin, Murray A. Raskind, Carol A. Miller, Ekaterina Rogaeva, Carlos Cruchaga, Joshua W. Miller, Matthew J. Huentelman, Joseph E. Parisi, Charles C. DeCarli, Eliezer Masliah, Didier Hannequin, Deborah Blacker, Michael L. Shelanski, Roger L. Albin, Mary Sano, Paul K. Crane, David G. Clark, Jean Paul G. Vonsattel, Mary Ganguli, John Hardy, John Powell, Charles DeCarli, Ronald C. Kim, Charles D. Smith, Jonathan D. Glass, M. Ilyas Kamboh, Steven E. Arnold, Gyungah Jun, Gail P. Jarvik, Anna Karydas, Suzee E. Lee, Carol F. Lippa, Allan I. Levey, Eckhard Mandelkow, Petra Nowotny, Dennis W. Dickson, Jennifer Williamson, John Q. Trojanowski, Isabelle Le Ber, Zbigniew K. Wszolek, Jeffrey Kaye, Eric B. Larson, Matthew P. Frosch, Harry V. Vinters, David A. Bennett, Joseph D. Buxbaum, Sandra Weintraub, Charles L. White, Lindy E. Harrell, Jonathan L. Haines, Minerva M. Carrasquillo, Robert O. Kenet, Lindsay A. Farrer, Robert C. Green, Wayne C. McCormick, Richard Mayeux, Denis A. Evans, Erik D. Roberson, Bruno Giordani, Liana G. Apostolova, Virginia M.-Y. Lee, Elizabeth Finger, Subashchandrabose Chinnathambi, Clinton T. Baldwin, Satish Kumar, Christiane Reitz, Steven H. Ferris, Randall L. Woltjer, Li-San Wang, Elaine R. Peskind, Thomas D. Bird, Eden R. Martin, Ryan J. Uitti, Martin R. Farlow, Amanda J. Myers, Jason J. Corneveaux, Gary W. Beecham, James D. Bowen, Juan C. Troncoso, Daniel H. Geschwind, Ann C. McKee, Roger N. Rosenberg, Bruce L. Miller, Daniel C. Marson, Jeffrey L. Cummings, Salvatore Spina, Regina M. Carney, Lee-Way Jin, Yvette Bordelon, Jean Paul Vonsattel, John R. Gilbert, Simon Lovestone, Kelley Faber, Mario F. Mendez, Laura B. Cantwell, Philip L. De Jager, John M. Ringman, Elizabeth Head, Wendy J. Mack, Giovanni Coppola, Nigel J. Cairns, Nilufer Ertekin-Taner, Nancy Johnson, Jacqueline L. Buros, Wallace W. Tourtellotte, Julie A. Schneider, Rosa Rademakers, Malcolm B. Dick, Ian R. A. Mackenzie, Andrew J. Saykin, Bradley F. Boeve, John S. K. Kauwe, Neil W. Kowall, Eva Maria Mandelkow, Andrew Kertesz, Lon S. Schneider, Joseph F. Quinn, F. Yesim Demirci, John C. Morris, Barry Reisberg, Andrew P. Lieberman, Bernardino Ghetti, Kathleen A. Welsh-Bohmer, Edward H. Koo, Alden Y. Huang, Walter A. Kukull, Alexis Brice, Eileen H. Bigio, M.-Marsel Mesulam, Steven T. DeKosky, Jorge L. Juncos, Neil Graff-Radford, M. Michael Barmada, Rudolph E. Tanzi, Owen A. Ross, Jason Karlawish, Tatiana Foroud, William W. Seeley, James J. Lah, Deborah C. Mash, Chuanhai Cao, Daniel P. Perl, A. Boxer, Matt Baker, Steven G. Younkin, Ronald L. Hamilton, Renee L. Sears, Jessica Lane, and Alzheimer's Dis Genetics Consortiu
Subjects: Risk, Genotype, epidemiology [Alzheimer Disease], Tau protein, epidemiology [Frontotemporal Dementia], Locus (genetics), genetics [Alzheimer Disease], MAPT protein, human, tau Proteins, Disease, Progressive supranuclear palsy, Alzheimer Disease, ddc:570, Genetic variation, Rare mutations, mental disorders, Genetics, medicine, Humans, Genetic Predisposition to Disease, Molecular Biology, Gene, Biology, genetics [Frontotemporal Dementia], Genetics (clinical), Aged, biology, Association Studies Articles, Genetic Variation, General Medicine, Middle Aged, medicine.disease, eye diseases, nervous system diseases, Chemistry, genetics [tau Proteins], Haplotypes, Clinical diagnosis, Frontotemporal Dementia, biology.protein, Human medicine
Abstract: Rare mutations in the gene encoding for tau (MAPT, microtubule-associated protein tau) cause frontotemporal dementia-spectrum (FTD-s) disorders, including FTD, progressive supranuclear palsy (PSP) and corticobasal syndrome, and a common extended haplotype spanning across the MAPT locus is associated with increased risk of PSP and Parkinson's disease. We identified a rare tau variant (p.A152T) in a patient with a clinical diagnosis of PSP and assessed its frequency in multiple independent series of patients with neurodegenerative conditions and controls, in a total of 15 369 subjects. Tau p.A152T significantly increases the risk for both FTD-s (n = 2139, OR = 3.0, CI: 1.6-5.6, P = 0.0005) and Alzheimer's disease (AD) (n = 3345, OR = 2.3, CI: 1.3-4.2, P = 0.004) compared with 9047 controls. Functionally, p.A152T (i) decreases the binding of tau to microtubules and therefore promotes microtubule assembly less efficiently; and (ii) reduces the tendency to form abnormal fibers. However, there is a pronounced increase in the formation of tau oligomers. Importantly, these findings suggest that other regions of the tau protein may be crucial in regulating normal function, as the p.A152 residue is distal to the domains considered responsible for microtubule interactions or aggregation. These data provide both the first genetic evidence and functional studies supporting the role of MAPT p.A152T as a rare risk factor for both FTD-s and AD and the concept that rare variants can increase the risk for relatively common, complex neurodegenerative diseases, but since no clear significance threshold for rare genetic variation has been established, some caution is warranted until the findings are further replicated.
Published: 2012
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31. National outbreak of Salmonella serotype saintpaul infections: importance of Texas restaurant investigations in implicating jalapeño peppers

Author: Adrianne Sever, Lou Franklin, Gerhard Falkenhorst, Val Jefferson, Jana L. Austin, Ingrid Zambrana, Angie Gass, Ian T. Williams, Robert M. Hoekstra, Kathleen Wannemuehler, Patricia M. Griffin, Kristin Delea, Brian P. Emanuel, Laura B. Cantwell, Karen M Herman, David L. Swerdlow, René Wood, Sharon A Greene, Amy Cone, Sarah Pichette, Samir V. Sodha, Rajal K. Mody, Sufian F. Al-Khaldi, Thi Dang, Isaac McCullum, Casey Barton Behravesh, Linda Gaul, and J. Christopher Yee
Subjects: Serotype, Bacterial Diseases, Male, Research Report, Salmonella, Veterinary medicine, Salmonellosis, Restaurants, Epidemiology, lcsh:Medicine, medicine.disease_cause, Disease Outbreaks, Gastrointestinal Infections, Child, lcsh:Science, Epidemiological Methods, Molecular Epidemiology, Multidisciplinary, Salmonella enterica, Middle Aged, Texas, Infectious Diseases, Child, Preschool, Salmonella Infections, Medicine, Female, Salmonella Food Poisoning, Public Health, Bacterial and Foodborne Illness, Capsicum, Research Article, Disease Ecology, Adult, medicine.medical_specialty, Infectious Disease Control, Adolescent, Gastroenterology and Hepatology, Infectious Disease Epidemiology, Young Adult, Environmental health, medicine, Humans, Serotyping, Aged, business.industry, lcsh:R, Case-control study, Pulsenet, Outbreak, Odds ratio, Case-Control Studies, lcsh:Q, business
Abstract: BACKGROUND: In May 2008, PulseNet detected a multistate outbreak of Salmonella enterica serotype Saintpaul infections. Initial investigations identified an epidemiologic association between illness and consumption of raw tomatoes, yet cases continued. In mid-June, we investigated two clusters of outbreak strain infections in Texas among patrons of Restaurant A and two establishments of Restaurant Chain B to determine the outbreak's source. METHODOLOGY/PRINCIPAL FINDINGS: We conducted independent case-control studies of Restaurant A and B patrons. Patients were matched to well controls by meal date. We conducted restaurant environmental investigations and traced the origin of implicated products. Forty-seven case-patients and 40 controls were enrolled in the Restaurant A study. Thirty case-patients and 31 controls were enrolled in the Restaurant Chain B study. In both studies, illness was independently associated with only one menu item, fresh salsa (Restaurant A: matched odds ratio [mOR], 37; 95% confidence interval [CI], 7.2-386; Restaurant B: mOR, 13; 95% CI 1.3-infinity). The only ingredient in common between the two salsas was raw jalapeño peppers. Cultures of jalapeño peppers collected from an importer that supplied Restaurant Chain B and serrano peppers and irrigation water from a Mexican farm that supplied that importer with jalapeño and serrano peppers grew the outbreak strain. CONCLUSIONS/SIGNIFICANCE: Jalapeño peppers, contaminated before arrival at the restaurants and served in uncooked fresh salsas, were the source of these infections. Our investigations, critical in understanding the broader multistate outbreak, exemplify an effective approach to investigating large foodborne outbreaks. Additional measures are needed to reduce produce contamination.
Published: 2011

32. Listening to Children

Author: L Trinder and B Cantwell
Subjects: Work (electrical), media_common.quotation_subject, Family court, Active listening, Psychology, Law, Social psychology, Welfare, media_common
Abstract: Brian Cantwell, Senior Family Court Welfare Officer in Humberside, and Liz Trinder, Research and Development Officer with Save the Children North and East Division in Hull, report the initial findings of their recent research survey of court welfare work. The Children Act's requirement upon courts to have regard to the ascertainable wishes and feelings of the child in contested applications has clearly places renewed practitioner emphasis on ascertaining children's wishes, but there remains considerable variation in interpretation of 'good practice'.
Published: 1993
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33. Meta-Analysis confirms CR1, CLU, and PICALM as Alzheimer’s disease risk loci and reveals interactions with APOE genotypes

Author: Hakon Hakonarson, Lindsay A. Farrer, Kathryn L. Lunetta, Deborah Blacker, Beth A. Dombroski, Rivka Inzelberg, Richard Mayeux, David A. Bennett, Adam C. Naj, Patricia L. Kramer, Duane Beekly, Gyungah Jun, Nilufer Ertekin-Taner, Jonathan L. Haines, L. Adrienne Cupples, Alison Goate, Walter A. Kukull, Jacqueline L. Buros, Tatiana Foroud, Gerard D. Schellenberg, Debby W. Tsuang, Thomas J. Montine, Peter St George-Hyslop, Ekaterina Rogaeva, Eric M. Reiman, M. Daniele Fallin, Margaret A. Pericak-Vance, Li-San Wang, Paul Gallins, Joseph D. Buxbaum, John C. Morris, Gary W. Beecham, Robert P. Friedland, Andrew J. Saykin, Laura B. Cantwell, and Eden R. Martin
Subjects: Apolipoprotein E, Male, Genotype, Genome-wide association study, Single-nucleotide polymorphism, Polymorphism, Single Nucleotide, Article, White People, PICALM, Cohort Studies, Apolipoproteins E, Arts and Humanities (miscellaneous), Gene Frequency, Meta-Analysis as Topic, Alzheimer Disease, Risk Factors, Confidence Intervals, Odds Ratio, Medicine, SNP, Humans, Risk factor, Allele frequency, Aged, Genetics, Aged, 80 and over, business.industry, Odds ratio, Clusterin, Monomeric Clathrin Assembly Proteins, Receptors, Complement 3b, Female, Neurology (clinical), business, Genome-Wide Association Study
Abstract: Objectives To determine whether genotypes at CLU, PICALM, and CR1 confer risk for Alzheimer disease (AD) and whether risk for AD associated with these genes is influenced by apolipoprotein E (APOE) genotypes. Design Association study of AD and CLU, PICALM, CR1, and APOE genotypes. Setting Academic research institutions in the United States, Canada, and Israel. Participants Seven thousand seventy cases with AD, 3055 with autopsies, and 8169 elderly cognitively normal controls, 1092 with autopsies, from 12 different studies, including white, African American, Israeli-Arab, and Caribbean Hispanic individuals. Results Unadjusted, CLU (odds ratio [OR], 0.91; 95% confidence interval [CI], 0.85-0.96 for single-nucleotide polymorphism [SNP] rs11136000), CR1 (OR, 1.14; 95% CI, 1.07-1.22; SNP rs3818361), and PICALM (OR, 0.89; 95% CI, 0.84-0.94, SNP rs3851179) were associated with AD in white individuals. None were significantly associated with AD in the other ethnic groups. APOE e4 was significantly associated with AD (ORs, 1.80-9.05) in all but 1 small white cohort and in the Arab cohort. Adjusting for age, sex, and the presence of at least 1 APOE e4 allele greatly reduced evidence for association with PICALM but not CR1 or CLU. Models with the main SNP effect, presence or absence of APOE e4, and an interaction term showed significant interaction between presence or absence of APOE e4 and PICALM. Conclusions We confirm in a completely independent data set that CR1, CLU, and PICALM are AD susceptibility loci in European ancestry populations. Genotypes at PICALM confer risk predominantly in APOE e4-positive subjects. Thus, APOE and PICALM synergistically interact.
Published: 2010

34. The effect of different recall periods on estimates of acute gastroenteritis in the United States, FoodNet Population Survey 2006–2007

Author: Elaine Scallan, Olga L. Henao, Robert M. Hoekstra, and Laura B. Cantwell
Subjects: Adult, Diarrhea, Male, Pediatrics, medicine.medical_specialty, Time Factors, Adolescent, Population, Prevalence, Applied Microbiology and Biotechnology, Microbiology, Epidemiology, medicine, Humans, education, Child, Population survey, Aged, Aged, 80 and over, education.field_of_study, Recall, business.industry, Infant, Acute gastroenteritis, Middle Aged, Health Surveys, United States, Gastroenteritis, Telephone, Telephone survey, Child, Preschool, Acute Disease, Food Microbiology, Animal Science and Zoology, Female, medicine.symptom, business, Food Science, Demography
Abstract: A number of countries have estimated the prevalence of acute gastroenteritis by asking survey respondents to recall past episodes of diarrhea; however, the recall period used varies between studies. We conducted a survey to examine the effects of 7-day and 1-month recall periods on the estimated annual episodes of acute gastroenteritis. Further, we examine whether asking first about illness in the previous 7 days affects a person's response to a 1-month recall period.The Foodborne Diseases Active Surveillance Network (FoodNet) conducted a population-based telephone survey that included asking respondents about the occurrence of gastrointestinal symptoms. From February through April 2007, we randomly split respondents into two groups to examine effect of recall periods and question order. One group was first asked about symptoms in the 7 days before interview and then asked about symptoms in the month before interview. The other group was asked only about symptoms in the month before interview.Overall, the monthly prevalence of acute diarrheal illness (≥3 loose stools in 24-hours, lasting1 day, or restricting daily activities) was 7.7%. This proportion was consistent among the respondents who were first asked about a 7-day recall period (n=1436) and those asked only about symptoms in the past month (n=2132). Extrapolation from the reported 7-day prevalence of 3.1% to an annual rate of 1.6 episodes per person, however, was almost twice the rate of episodes estimated when extrapolating from the month recall period. Similar findings were found with acute gastroenteritis (acute diarrheal illness or vomiting without respiratory symptoms).First asking respondents about a 7-day recall period did not affect the prevalence of acute gastroenteritis reported for a 1-month recall period. Recall period length did, however, have a major impact on estimates of acute gastroenteritis. Retrospective studies using different recall periods may not be comparable.
Published: 2010

35. Rarity of the Alzheimer Disease–ProtectiveAPPA673T Variant in the United States

Author: Nigel J. Cairns, Maria C. Norton, Eric B. Larson, Eliezer Masliah, Julie A. Schneider, Malcolm B. Dick, John S. K. Kauwe, Marilyn S. Albert, Neil W. Kowall, Amanda Partch, JoAnn T. Tschanz, Lindsay A. Farrer, Wayne W. Poon, Nilufer Ertekin-Taner, Barry Reisberg, Timothy W. Behrens, Huntington Potter, Kenneth B. Fallon, Brian W. Kunkle, Duane Beekly, Adam C. Naj, Frank Martiniuk, Marla Gearing, Andrew P. Lieberman, Jonathan L. Haines, Ronald L. Hamilton, David G. Clark, Peter St George-Hyslop, Martin R. Farlow, Lisa L. Barnes, Murray A. Raskind, Deborah Blacker, Aimee Pierce, Bernardino Ghetti, Kathleen A. Welsh-Bohmer, Patricia L. Kramer, Joseph F. Quinn, Eric M. Reiman, Matthew P. Frosch, Kathryn L. Lunetta, Gail P. Jarvik, Roger N. Rosenberg, John Q. Trojanowski, Alison Goate, John H. Growdon, Linda J. Van Eldik, Roger L. Albin, Liana G. Apostolova, Christine M. Hulette, Eileen H. Bigio, William Perry, Josue D. Gonzalez Murcia, Clinton B. Wright, Allan I. Levey, Margaret A. Pericak-Vance, Ashok Raj, Jennifer Williamson, Clinton T. Baldwin, Oscar L. Lopez, James R. Burke, Joel H. Kramer, Edward H. Koo, Bradley T. Hyman, Tatiana Foroud, Vivianna M. Van Deerlin, James B. Leverenz, William W. Seeley, Paul K. Crane, Sarah Wishnek, Debby W. Tsuang, Christopher S. Carlson, F. Yesim Demirci, Steven H. Ferris, Charles DeCarli, Laura B. Cantwell, John M. Ringman, Carol A. Miller, Li-San Wang, Mary Sano, M. Ilyas Kamboh, Lisa A. Cannon-Albright, Elizabeth Crocco, R. C. Kim, Gyungah Jun, Anna Karydas, John M Olichney, James T. Becker, Randall L. Woltjer, Carlos Cruchaga, Joshua W. Miller, Elaine R. Peskind, Robert R. Graham, Steven E. Arnold, Joseph D. Buxbaum, Tricia A. Thornton-Wells, Kaj Blennow, Robert C. Green, Gerard D. Schellenberg, Erik D. Roberson, Gary W. Beecham, Douglas Galasko, Beth A. Dombroski, Thomas G. Beach, Wendy J. Mack, Eden R. Martin, John C. Morris, Badri N. Vardarajan, Daniel H. Geschwind, Daniel C. Marson, Jill R. Murrell, Chuanhai Cao, David A. Bennett, Ann C. McKee, Neill R. Graff-Radford, Robert S. Stern, Lee-Way Jin, Constantine G. Lyketsos, Salvatore Spina, Ekaterina Rogaeva, Wayne C. McCormick, Jean Paul Vonsattel, Mary Ganguli, Elizabeth Head, Chris Corcoran, Lei Yu, Ranjan Duara, Kelley Faber, Andrew McDavid, Helena C. Chui, John R. Gilbert, Amanda G. Smith, Chang-En Yu, Robert Barber, Richard Mayeux, James D. Bowen, Hakon Hakonarson, Juan C. Troncoso, Dennis W. Dickson, Ronald C. Petersen, Deborah C. Mash, Bruce L. Miller, Henrik Zetterberg, Joshua A. Sonnen, Jeffrey Kaye, M. Michael Barmada, L. Schneider, Rudolph E. Tanzi, Otto Valladares, Andrew J. Saykin, Ronald G. Munger, Thomas J. Montine, A. Boxer, Steven G. Younkin, Harry V. Vinters, Frank M. LaFerla, Nicole Schupf, Christiane Reitz, Walter A. Kukull, Chiao-Feng Lin, Kara L. Hamilton-Nelson, M.-Marsel Mesulam, Steven T. DeKosky, Howard J. Rosen, Lawrence S. Honig, Steven L. Carroll, Susan M. McCurry, Joseph E. Parisi, Thomas D. Bird, James J. Lah, Bradley F. Boeve, Gregory A. Jicha, Jonathan D. Glass, Regina M. Carney, Sandra Weintraub, David H. Cribbs, Lindy E. Harrell, and Ge Li
Subjects: Male, medicine.medical_specialty, Genotype, Population, Locus (genetics), Article, Amyloid beta-Protein Precursor, Alzheimer Disease, Internal medicine, Medicine and Health Sciences, medicine, Humans, Allele, education, Prospective cohort study, Aged, Genetic association, Aged, 80 and over, Sweden, Genetics, education.field_of_study, business.industry, Case-control study, Protective Factors, medicine.disease, United States, Pedigree, Case-Control Studies, Female, Neurology (clinical), Alzheimer's disease, Age of onset, business
Abstract: Importance Recently, a rare variant in the amyloid precursor protein gene ( APP ) was described in a population from Iceland. This variant, in which alanine is replaced by threonine at position 673 (A673T), appears to protect against late-onset Alzheimer disease (AD). We evaluated the frequency of this variant in AD cases and cognitively normal controls to determine whether this variant will significantly contribute to risk assessment in individuals in the United States. Objective To determine the frequency of the APP A673T variant in a large group of elderly cognitively normal controls and AD cases from the United States and in 2 case-control cohorts from Sweden. Design, Setting, and Participants Case-control association analysis of variant APP A673T in US and Swedish white individuals comparing AD cases with cognitively intact elderly controls. Participants were ascertained at multiple university-associated medical centers and clinics across the United States and Sweden by study-specific sampling methods. They were from case-control studies, community-based prospective cohort studies, and studies that ascertained multiplex families from multiple sources. Main Outcomes and Measures Genotypes for the APP A673T variant were determined using the Infinium HumanExome V1 Beadchip (Illumina, Inc) and by TaqMan genotyping (Life Technologies). Results The A673T variant genotypes were evaluated in 8943 US AD cases, 10 480 US cognitively normal controls, 862 Swedish AD cases, and 707 Swedish cognitively normal controls. We identified 3 US individuals heterozygous for A673T, including 1 AD case (age at onset, 89 years) and 2 controls (age at last examination, 82 and 77 years). The remaining US samples were homozygous for the alanine (A673) allele. In the Swedish samples, 3 controls were heterozygous for A673T and all AD cases were homozygous for the A673 allele. We also genotyped a US family previously reported to harbor the A673T variant and found a mother-daughter pair, both cognitively normal at ages 72 and 84 years, respectively, who were both heterozygous for A673T; however, all individuals with AD in the family were homozygous for A673. Conclusions and Relevance The A673T variant is extremely rare in US cohorts and does not play a substantial role in risk for AD in this population. This variant may be primarily restricted to Icelandic and Scandinavian populations.
Published: 2015
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36. Effects of Multiple Genetic Loci on Age at Onset in Late-Onset Alzheimer Disease

Author: Gail P. Jarvik, David G. Clark, John Hardy, Allan I. Levey, Jennifer Williamson, David A. Bennett, Richard Mayeux, Matthew P. Frosch, Mary Ganguli, Deborah C. Mash, Bruce L. Miller, Andrew McDavid, John R. Gilbert, Linda J. Van Eldik, Walter A. Kukull, Chiao-Feng Lin, Kara L. Hamilton-Nelson, M.-Marsel Mesulam, Steven T. DeKosky, Howard J. Rosen, Gyungah Jun, Anna Karydas, Robert Barber, Hakon Hakonarson, Steven H. Ferris, Li-San Wang, Nilufer Ertekin-Taner, Wendy J. Mack, Roger N. Rosenberg, Lei Yu, Ranjan Duara, Helena C. Chui, Christiane Reitz, Martin R. Farlow, Nigel J. Cairns, Steven G. Younkin, Laura B. Cantwell, Robert S. Stern, Jason J. Corneveaux, Minerva M. Carrasquillo, Joseph D. Buxbaum, Thomas G. Beach, Gary W. Beecham, Elaine R. Peskind, Ekaterina Rogaeva, Thomas D. Bird, Daniel H. Geschwind, Christopher S. Carlson, Jill R. Murrell, Carol A. Miller, Amanda J. Myers, Barry Reisberg, James D. Bowen, Ann C. McKee, Robert C. Green, Oscar L. Lopez, Brian W. Kunkle, Adam C. Naj, Frank Martiniuk, Christine M. Hulette, James T. Becker, F. Yesim Demirci, Lisa L. Barnes, Joel H. Kramer, William Perry, Kenneth B. Fallon, Gregory A. Jicha, Wayne C. McCormick, James R. Burke, Jean Paul Vonsattel, Jonathan D. Glass, Duane Beekly, Ronald C. Petersen, Badri N. Vardarajan, Joshua A. Sonnen, Paul K. Crane, Ronald L. Hamilton, Patricia L. Kramer, Eric B. Larson, John C. Morris, Lee-Way Jin, Kelley Faber, Salvatore Spina, Lawrence S. Honig, Regina M. Carney, Huntington Potter, Julie A. Schneider, Joseph F. Quinn, Alison Goate, Malcolm B. Dick, Bernardino Ghetti, Kathleen A. Welsh-Bohmer, YoSon Park, John S. K. Kauwe, Tatiana Foroud, Eileen H. Bigio, Thomas J. Montine, Philip L. De Jager, Edward H. Koo, Murray A. Raskind, William W. Seeley, Sandra Weintraub, Neil W. Kowall, Chuanhai Cao, Aimee Pierce, David H. Cribbs, Lindy E. Harrell, Neill R. Graff-Radford, Lon S. Schneider, Roger L. Albin, Randall L. Woltjer, James B. Leverenz, Elizabeth Crocco, Constantine G. Lyketsos, John M. Ringman, Ge Li, Dennis W. Dickson, Lindsay A. Farrer, Clinton B. Wright, Margaret A. Pericak-Vance, Ashok Raj, Jonathan L. Haines, Sarah Wishnek, Charles DeCarli, Rudolph E. Tanzi, Eden R. Martin, Chang En Yu, Susan M. McCurry, M. Ilyas Kamboh, Elizabeth Head, John H. Growdon, Liana G. Apostolova, Vivianna M. Van Deerlin, Steven E. Arnold, Jeffrey Kaye, Henry L. Paulson, Debby W. Tsuang, Juan C. Troncoso, Harry V. Vinters, Clinton T. Baldwin, Eliezer Masliah, Otto Valladares, Andrew J. Saykin, Frank M. LaFerla, Carlos Cruchaga, M. Michael Barmada, John Q. Trojanowski, Matthew J. Huentelman, Marilyn S. Albert, Bradley T. Hyman, Ruchita Rajbhandary, Mary Sano, Peter St George-Hyslop, Adam L. Boxer, Gerard D. Schellenberg, Douglas Galasko, Marla Gearing, James J. Lah, Bradley F. Boeve, Vernon S. Pankratz, Joshua W. Miller, Denis A. Evans, Steven L. Carroll, Joseph E. Parisi, Wayne W. Poon, Deborah Blacker, R. C. Kim, Erik D. Roberson, Tricia A. Thornton-Wells, Andrew P. Lieberman, Eric M. Reiman, Amanda Smith, Kathryn L. Lunetta, and John M Olichney
Subjects: Adult, Male, Apolipoprotein E, Oncology, medicine.medical_specialty, Genotype, Population, Genome-wide association study, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Article, PICALM, Alzheimer Disease, Risk Factors, Internal medicine, medicine, Humans, Genetic Predisposition to Disease, Prospective Studies, Age of Onset, education, Aged, Genetic association, Aged, 80 and over, Genetics, education.field_of_study, Middle Aged, Genetic Loci, Meta-analysis, Female, Neurology (clinical), Age of onset, Genome-Wide Association Study
Abstract: Importance Because APOE locus variants contribute to risk of late-onset Alzheimer disease (LOAD) and to differences in age at onset (AAO), it is important to know whether other established LOAD risk loci also affect AAO in affected participants. Objectives To investigate the effects of known Alzheimer disease risk loci in modifying AAO and to estimate their cumulative effect on AAO variation using data from genome-wide association studies in the Alzheimer Disease Genetics Consortium. Design, Setting, and Participants The Alzheimer Disease Genetics Consortium comprises 14 case-control, prospective, and family-based data sets with data on 9162 participants of white race/ethnicity with Alzheimer disease occurring after age 60 years who also had complete AAO information, gathered between 1989 and 2011 at multiple sites by participating studies. Data on genotyped or imputed single-nucleotide polymorphisms most significantly associated with risk at 10 confirmed LOAD loci were examined in linear modeling of AAO, and individual data set results were combined using a random-effects, inverse variance–weighted meta-analysis approach to determine whether they contribute to variation in AAO. Aggregate effects of all risk loci on AAO were examined in a burden analysis using genotype scores weighted by risk effect sizes. Main Outcomes and Measures Age at disease onset abstracted from medical records among participants with LOAD diagnosed per standard criteria. Results Analysis confirmed the association of APOE with earlier AAO ( P = 3.3 × 10 −96 ), with associations in CR1 (rs6701713, P = 7.2 × 10 −4 ), BIN1 (rs7561528, P = 4.8 × 10 −4 ), and PICALM (rs561655, P = 2.2 × 10 −3 ) reaching statistical significance ( P APOE contributes to 3.7% of the variation in AAO ( R2 = 0.256) over baseline ( R2 = 0.221), whereas the other 9 loci together contribute to 2.2% of the variation ( R2 = 0.242). Conclusions and Relevance We confirmed an association of APOE (OMIM107741) variants with AAO among affected participants with LOAD and observed novel associations of CR1 (OMIM 120620), BIN1 (OMIM 601248), and PICALM (OMIM 603025) with AAO . In contrast to earlier hypothetical modeling, we show that the combined effects of Alzheimer disease risk variants on AAO are on the scale of, but do not exceed, the APOE effect. While the aggregate effects of risk loci on AAO may be significant, additional genetic contributions to AAO are individually likely to be small.
Published: 2014
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37. Prevalence of persistent asymptomatic proteinuria in HIV-infected outpatients and lack of correlation with viral load

Author: S T, Crowley, B, Cantwell, A, Abu-Alfa, and M O, Rigsby
Subjects: Male, Proteinuria, HIV Seropositivity, Humans, Female, HIV Infections, AIDS-Associated Nephropathy, Middle Aged, Viral Load, CD4 Lymphocyte Count
Abstract: Human immunodeficiency virus-associated nephropathy (HIVAN) is projected to be a leading cause of end-stage renal disease (ESRD) in young African American men in the new millennium. Little is known about the early natural history of the disease, including the prevalence of asymptomatic nephropathy. The primary aim of this study was to define the prevalence of persistent asymptomatic proteinuria in a contemporary, ambulatory human immunodeficiency virus- (HIV) infected population. The secondary aim was to correlate the presence of persistent proteinuria with measures of HIV disease.Using a readily available screening tool, the urine dipstick, we determined the prevalence of persistent asymptomatic proteinuria in the outpatient VA Connecticut (VA CT) Healthcare System West Haven HIV Clinic population. We compared the presence of persistent proteinuria with measures of HIV viral disease.The prevalence of persistent asymptomatic proteinuria was 14% (7 of 49 patients). The presence of persistent proteinuria was not correlated with viral load.A significant prevalence of occult renal disease exists in the asymptomatic HIV-seropositive outpatient population and is not correlated with viral load.
Published: 2001

38. National Ignition Facility pollution prevention and waste minimization plan

Author: J. Celeste and B. Cantwell
Subjects: Waste generation, Engineering, business.industry, Action plan, Pollution prevention, Environmental engineering, Milestone (project management), Plan (drawing), Minification, business, National Ignition Facility, National laboratory, Construction engineering
Abstract: This document is the Lawrence Livermore National Laboratory (LLNL) National Ignition Facility (NIF) Pollution Prevention and Waste Minimization Plan. It will not only function as the planning document for anticipating, minimizing, and mitigating NIF waste generation, but it is also a Department of Energy (DOE) milestone document specified in the facility's Mitigation Action Plan (MAP). As such, it is one of the ''living'' reference documents that will guide NIF operations through all phases of the project. This document will be updated periodically to reflect development of the NIF, from construction through lifetime operations.
Published: 1998
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39. Variants in the ATP-Binding Cassette Transporter (ABCA7), Apolipoprotein E ϵ4, and the Risk of Late-Onset Alzheimer Disease in African Americans

Author: Jill R. Murrell, Tatiana Foroud, Rodney C.P. Go, Oscar L. Lopez, Mark W. Logue, Paul K. Crane, Gyungah Jun, Goldie S. Byrd, Gerard D. Schellenberg, Li-San Wang, Badri N. Vardarajan, Patrick A. Griffith, Jennifer J. Manly, Kathleen S. Hall, M. Daniele Fallin, Laura B. Cantwell, Towfique Raj, Kathryn L. Lunetta, Ruchita Rajbhandary, Philip L. De Jager, Jonathan L. Haines, Richard Mayeux, Lindsay A. Farrer, Denis A. Evans, Christiane Reitz, Thomas O. Obisesan, Clinton T. Baldwin, Eric B. Larson, Adam C. Naj, Nilufer Ertekin-Taner, Otto Valladares, Joseph D. Buxbaum, Robert C. Green, Margaret A. Pericak-Vance, Walter A. Kukull, Chiao-Feng Lin, David A. Bennett, Neill R. Graff-Radford, Alison Goate, M. Ilyas Kamboh, Hugh C. Hendrie, and Lisa L. Barnes
Subjects: Risk, Apolipoprotein E, Linkage disequilibrium, Genotype, Apolipoprotein E4, Genome-wide association study, Single-nucleotide polymorphism, Population stratification, Polymorphism, Single Nucleotide, Article, Linkage Disequilibrium, Alzheimer Disease, medicine, Humans, Genetic Predisposition to Disease, Age of Onset, Aged, Genetic testing, Genetics, medicine.diagnostic_test, business.industry, Genetic Variation, General Medicine, Middle Aged, medicine.disease, Black or African American, Case-Control Studies, ATP-Binding Cassette Transporters, Alzheimer's disease, Age of onset, business, Genome-Wide Association Study
Abstract: Genetic variants associated with susceptibility to late-onset Alzheimer disease are known for individuals of European ancestry, but whether the same or different variants account for the genetic risk of Alzheimer disease in African American individuals is unknown. Identification of disease-associated variants helps identify targets for genetic testing, prevention, and treatment.To identify genetic loci associated with late-onset Alzheimer disease in African Americans.The Alzheimer Disease Genetics Consortium (ADGC) assembled multiple data sets representing a total of 5896 African Americans (1968 case participants, 3928 control participants) 60 years or older that were collected between 1989 and 2011 at multiple sites. The association of Alzheimer disease with genotyped and imputed single-nucleotide polymorphisms (SNPs) was assessed in case-control and in family-based data sets. Results from individual data sets were combined to perform an inverse variance-weighted meta-analysis, first with genome-wide analyses and subsequently with gene-based tests for previously reported loci.Presence of Alzheimer disease according to standardized criteria.Genome-wide significance in fully adjusted models (sex, age, APOE genotype, population stratification) was observed for a SNP in ABCA7 (rs115550680, allele = G; frequency, 0.09 cases and 0.06 controls; odds ratio [OR], 1.79 [95% CI, 1.47-2.12]; P = 2.2 × 10(-9)), which is in linkage disequilibrium with SNPs previously associated with Alzheimer disease in Europeans (0.8D'0.9). The effect size for the SNP in ABCA7 was comparable with that of the APOE ϵ4-determining SNP rs429358 (allele = C; frequency, 0.30 cases and 0.18 controls; OR, 2.31 [95% CI, 2.19-2.42]; P = 5.5 × 10(-47)). Several loci previously associated with Alzheimer disease but not reaching significance in genome-wide analyses were replicated in gene-based analyses accounting for linkage disequilibrium between markers and correcting for number of tests performed per gene (CR1, BIN1, EPHA1, CD33; 0.0005empirical P.001).In this meta-analysis of data from African American participants, Alzheimer disease was significantly associated with variants in ABCA7 and with other genes that have been associated with Alzheimer disease in individuals of European ancestry. Replication and functional validation of this finding is needed before this information is used in clinical settings.
Published: 2013
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40. Sexually Aggressive Children and Societal Response

Author: Hendrika B. Cantwell
Subjects: Psychology
Published: 1995
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41. Inaugural national scientific medical meeting

Author: P. Noonan Walsh, C. Conliffe, A. S. Abdulkadir, P. Kelehan, R. Conroy, M. Foley, P. Lenehan, J. F. Murphy, J. Stronge, B. Cantwell, C. Wright, M. Millward, M. Carpenter, T. Lennard, R. Wilson, C. Home, A. R. Corbett, G. O’Sullivan, J. K. Collins, M. Doran, E. W. M. McDermott, P. Mercer, P. Smyth, N. J. O’Higgins, M. J. Duffy, D. Reilly, E. McDermott, C. Faul, J. J. Fennelly, N. O’Higgins, S. Lowry, H. Russell, R. Atkinson, I. Hickey, F. O’Brien, A. O’Mahony, M. O’Donoghue, M. Pomeroy, E. S. Prosser, F. Barker, M. Casey, K. Carroll, M. Davis, G. Duffy, R. O’Kennedy, P. P. A. Smyth, D. O’Carroll, A. M. Hetherton, E. Coveney, V. McAlister, M. J. Murray, D. J. Brayden, A. O’Hora, J. Street, J. O’Leary, A. M. Pollock, M. Crowley, I. Healy, J. Murphy, R. Landers, L. Burke, D. O’Brien, P. Annis, J. Hogan, W. Kealy, F. A. Lewis, C. T. Doyle, M. Callaghan, A. Whelan, C. Feighery, B. Bresnihan, D. Kelleher, G. Reams, A. Murphy, N. Hall, E. B. Casey, D. Mulherin, E. Doherty, G. Yanni, E. Wallace, J. Jackson, M. Bennett, O. Tighe, H. Mulcahy, D. O’Donoghue, D. T. Croke, R. J. Cahill, S. Beattie, H. Hamilton, C. O’Morain, B. Corridan, R. A. Collins, C. A. O’Morain, E. Fitzgerald, J. M. Gilvarry, M. Leader, J. F. Fielding, B. T. Johnson, S. A. Lewis, A. H. G. Love, B. T. Johnston, J. S. A. Collins, R. J. McFarland, P. W. Johnston, B. J. Collins, C. M. Kilgallen, G. M. Murphy, G. M. Markey, J. A. McCormack, R. C. Curry, T. C. M. Morris, H. D. Alexander, S. Edgar, M. Treacy, M. A. O’Connell, D. G. Weir, J. Sheehan, G. O’Loughlin, O. Traynor, N. Walsh, H. X. Xia, M. A. Daw, C. T. Keane, C. Dupont, G. Gibson, E. McGinnity, J. Walshe, M. Carmody, J. Donohoe, P. McGrath, R. O’Moore, E. Kieran, S. Rogers, K. E. McKenna, M. Walsh, E. A. Bingham, A. E. Hughes, N. C. Nevin, D. J. Todd, C. F. Stanford, M. E. Callender, D. Burrows, D. G. Paige, G. E. Allen, D. P. O’Brien, D. B. Gough, C. Phelan, H. F. Given, S. Zia Kamal, S. Kehoe, S. Coldicott, D. Luesley, K. Ward, H. F. MacDonnell, S. Mullins, I. Gordon, L. A. Norris, M. Devitt, J. Bonnar, S. C. Sharma, B. L. Sheppard, R. Fitzsimons, S. Kingston, M. Garvey, H. M. C. V. Hoey, J. F. T. Glasgow, R. Moore, P. H. Robinson, E. Murphy, J. F. A. Murphy, A. E. Wood, P. Sweeney, M. Neligan, D. MacLeod, G. Cunnane, P. Kelly, P. Corcoran, L. Clancy, R. M. Drury, M. I. Drury, D. Powell, R. G. R. Firth, T. Jones, B. F. Ferris, W. O’Flynn, J. O’Donnell, S. M. Kingston, F. Cunningham, G. M. E. Hinds, D. R. McCluskey, F. Howell, M. O’Mahony, J. Devlin, O. O’Reilly, C. Buttanshaw, S. Jennings, E. R. Keane, C. Foley-Nolan, F. M. Ryan, M. Taylor, R. A. Lyons, F. O’Kelly, J. Mason, D. Carroll, K. Doherty, M. Flynn, R. O’Dwyer, J. J. Gilmartin, C. F. McCarthy, C. Armstrong, D. Mannion, T. Feely, G. Fitzpatrick, C. M. Cooney, J. Chin Aleong, R. Rooney, J. Lyons, D. M. Phelan, G. P. Joshi, S. M. McCarroll, W. P. Blunnie, T. M. O’Brien, D. C. Moriarty, J. Brangan, C. P. Kelly, P. Kenny, H. Gallagher, E. McGovern, D. Luke, D. Lowe, T. Rice, D. Phelan, J. B. Lyons, F. M. Lyons, D. M. McCoy, J. McGinley, J. Hurley, P. McDonagh, J. J. Crowley, S. M. Donnelly, M. Tobin, O. Fitzgerald, B. J. Maurer, P. J. Quigley, G. King, E. B. Duly, T. R. Trinick, D. Boyle, G. B. Wisdom, F. Geoghegan, P. B. Collins, C. Goss, K. Younger, P. Mathias, I. Graham, S. W. MacGowan, P. Sidhu, D. J. McEneaney, D. J. Cochrane, A. A. J. Adgey, J. M. Anderson, J. Moriarty, C. Fahy, A. Lavender, L. Lynch, C. McGovern, A. M. Nugent, D. Neely, I. Young, I. McDowell, M. O’Kane, D. P. Nicholls, D. McEneaney, D. P. Nichols, N. P. S. Campbell, G. C. Campbell, M. I. Halliday, A. F. O’Donnell, M. Lonergan, T. Ahearne, J. O’Neill, T. V. Keaveny, D. Ramsbottom, D. Boucher-Hayes, R. Sheahan, M. T. Garadaha, D. Kidney, P. Freyne, G. Gearty, P. Crean, H. P. Singh, M. Hargrove, K. Subareddy, J. P. Hurley, W. O’Rourke, C. O’Connor, M. X. FitzGerald, T. J. McDonnell, R. Chan, J. Stinson, L. Hemeryck, J. Feely, M. P. Chopra, A. Sivner, S. M. Sadiq, E. Abernathy, L. Plant, C. P. Bredin, P. Hickey, G. Slevin, K. McCrory, M. Long, P. Conlon, F. Walker, P. Fitzgerald, S. J. O’Neill, C. M. O’Connor, C. Quigley, S. Donnelly, A. Southey, E. Healy, F. Mulcahy, D. J. Lyons, J. Keating, C. O’Mahony, D. Roy, A. G. Shattock, I. B. Hillary, A. Waiz, R. Hossain, B. Chakraborthy, L. P. Clancy, L. O’Reilly, C. Byrne, E. Costello, E. O’Shaughnessy, B. Cryan, J. Farrell, J. J. Walshe, G. J. Mellotte, C. A. Ho, S. H. Morgan, M. R. Bending, and J. Bonner
Subjects: Medical education, business.industry, Medicine, General Medicine, business, Article
Published: 1993
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42. Should fertile people have access to in vitro fertilisation?

Author: B Cantwell
Subjects: In vitro fertilisation, Letter, Multimedia, business.industry, medicine.medical_treatment, General Engineering, General Medicine, computer.software_genre, Biotechnology, General Earth and Planetary Sciences, Medicine, business, computer, General Environmental Science
Published: 1990

43. Irish Association for Cancer Research

Author: M. M. T. O’Hare, J. M. Sloan, D. Buchanan, B. Herity, J. Murphy, M. Moriarty, G. J. Bourke, L. Daly, R. J. Atkinson, W. S. Lowry, J. Dunne, A. Darragh, I. Brick, S. R. McCann, C. A. Whelan, B. Breslin, I. J. Temperley, J. J. Fennelly, B. Cantwell, M. Jones, Jack Phillips, Karol Sikora, M. Reynolds, S. R. M’cCann, M. O’Connell, L. McDonnell, E. Connolly, M. J. Duffy, R. Clark, H. W. Van den Berg+, R. F. Murphy, M. McCarthy, J. Cotter, L. Mullins, J. K. Collins, Lynn Gordon, G. O’Loughlin, Martin M. Clynes, Michael J. Moriarty, S. M. Lavelle, Maura Maclomhair, Bernadette Hannigan, Alan Johnson, Patrick Collins, Michael Moriarty, Mahomed Al-Sader, Rosaleen Devery, Ena Walsh, Honor Smyth, Antonia Corrigan, C. Ryan, C. Mothersill, and C. Seymour
Subjects: medicine.medical_specialty, Irish, business.industry, Association (object-oriented programming), Family medicine, language, Medicine, General Medicine, business, language.human_language
Published: 1982
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44. Irish Society of Gastroenterology

Author: J. M. Scott, D. G. Weir, J. Paterson, B. McNicholl, J. Waterhouse, P. G. Collins, G. A. E. Coupland, M. Bourke, G. Neale, F. McCarthy, T. J. Muscroft, Rachel McKenna, V. S. Brookes, J. A. H. Waterhouse, W. Kirwan, G. D. Oates, N. H. Teo, G. V. H. Bradby, D. J. Ellis, J. J. Fennelly, G. P. van Berge Henegouwen, N. J. Dorricott, P. Hawker, S. O. Domhnaill, J. Fielding, P. V. Delaney, E. D. Albert, P. Prior, M. J. Dew, J. W. L. Fielding, J. Alexander-Williams, D. Fry, H. Thompson, T. J. Egan, K. Atmatzidis, C. J. Martin, T. P. J. Hennessy, O. FitzGerald, S. A. Deane, E. W. Taylor, M. R. Keighley, B. Cantwell, F. M. Stevens, S. J. Heffernan, B. G. Jones, G. Slaney, J. Powell, S. Glyde, R. N. Allan, S. Nutter, and M. A. Anselmi
Subjects: medicine.medical_specialty, Pediatrics, geography, geography.geographical_feature_category, Irish, business.industry, Family medicine, Spring (hydrology), language, Medicine, General Medicine, business, language.human_language
Published: 1982
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45. Carcino-embryonic antigen assay as a guide to tumour bulk, response to therapy and prognosis in human breast cancer

Author: G.J. Duffy, Leslie Daly, M. Jones, James J. Fennelly, Michael J. Duffy, and B. Cantwell
Subjects: Oncology, medicine.medical_specialty, biology, Response to therapy, business.industry, Stage iv disease, Cancer, Breast Neoplasms, General Medicine, Disease, Prognosis, medicine.disease, Carcinoembryonic Antigen, Embryonic antigen, Breast cancer, Carcinoembryonic antigen, Internal medicine, medicine, biology.protein, Humans, Female, business, Human breast
Abstract: Serum carcinoembryonic antigen (CEA) levels were studied in 128 patients with histologically proven breast cancer. When measured at diagnosis in patients with non-metastatic disease (all stages except Stage IV) 27% of patients had levels greater than 10 ng/ ml. Measurement of the CEA at initial diagnosis gave little guide to which patients subsequently relapsed. Patients with Stage IV disease at diagnosis had levels in excess of 10 ng/ml in 75% of cases. Furthermore, changes in serum CEA levels were found to reflect changes in tumour bulk, in individual patients, in 75.8% of cases. It is concluded that while serial measurements of serum CEA levels can be of value, particularly in the management of advanced breast cancer patients, it is of less value in the earlier stages as a predicator of recurrence.
Published: 1980
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46. Proceedings of The Irish Association for Cancer Research Meeting

Author: J. P. Corridan, M. A. Moran, B. Herity, N. Hilliard, M. Moriarty, J. Fennelly, M. M. McCambridge, M. Casey, M. Quigley, S. Hunt, Lynn Gordon, W. S. Lowry, J. Prendiville, H. Raftery, P. Blake, A. Robinson, R. Conroy, M. Pomeroy, Bernadette Herity, J. F. Murphy, Leslie Daly, R. J. Atkinson, D. Kelly, M. McCabe, J. J. Fennelly, G. Duffy, F. Duff, J. Duffy, Maura Reynolds, S. R. McCann, P. Keeling, P. J. Byrne, K. Mealy, A. Whelan, C. Feighery, T. P. J. Hennessy, M. J. Duffy, M. O’Connell, B. Cantwell, L. O’Siorain, M. O’Ccnnel, J. Simon, M. G. Harrington, Li O’Siorain, S. O’Briain, S. McDonnell, M. Clynes, C. B. Seymour, C. Mothersill, P. Byrne, S. M. Lavelle, M. Mac Lomhair, D. O’Reilly, E. Mullins, S. Canty, J. K. Collins, J. Davis, J. Conroy, M. B. Keatinge, P. B. Collins, J. P. Duignan, B. Dickson, A. H. Johnson, A. McCann, C. Seymour, A. Long, D. O’Donoghue, S. Mulgrew, T. J. Conere, S. W. Church, Sidney Lowry, B. Earls, and R. J. Russell
Subjects: medicine.medical_specialty, Irish, business.industry, Family medicine, Association (object-oriented programming), language, medicine, General Medicine, business, language.human_language
Published: 1985
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47. Vaginal inspection as it relates to child sexual abuse in girls under thirteen

Author: Hendrika B. Cantwell
Subjects: Child abuse, medicine.medical_specialty, Adolescent, Poison control, Physical examination, Developmental and Educational Psychology, medicine, Humans, Child Abuse, Child, Psychiatry, Physical Examination, Sexual violence, medicine.diagnostic_test, Obstetrics, business.industry, Sex Offenses, Psychiatry and Mental health, medicine.anatomical_structure, Sexual abuse, Incest, Child, Preschool, Child sexual abuse, Vagina, Pediatrics, Perinatology and Child Health, Female, Sex offense, business
Abstract: Inclusion of vaginal inspection in all physical examinations resulted in doubling identification of cases of child sexual abuse. Forty-five of 247 girls under 13 years of age were admitted because sexual abuse had been reported. Of the 202 girls not suspected, 45 additional cases of sexual abuse were discovered by suspicious findings on vaginal inspection. The horizontal diameter of the vaginal opening exceeding 4 mm correlated in three of four instances with a confirming history for past sexual abuse. It is recommended that physical examination of young girls routinely include inspection of the vaginal opening. Pediatric caregivers need to teach themselves the parameters of the normal to protect those children who are suffering sexual abuse in their environment.
Published: 1983
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48. Sexual abuse of children in Denver, 1979: Reviewed with implications for pediatric intervention and possible prevention

Author: Hendrika B. Cantwell
Subjects: medicine.medical_specialty, business.industry, Poison control, Human factors and ergonomics, Suicide prevention, Occupational safety and health, Psychiatry and Mental health, Sexual abuse, Intervention (counseling), Pediatrics, Perinatology and Child Health, Injury prevention, Developmental and Educational Psychology, medicine, Sibling, Psychiatry, business
Abstract: 287 children involved in sexual abuse are reviewed. All were reported in Denver, Colorado, U.S.A., in 1979. Specific attention is given to the origin of the report of cases later determined to be unfounded. Sibling sexual involvement is examined, particularly with reference to the age differential. Perpetrators are categorized as fathers, stepfathers, mother's “boyfriend,” relatives or family friends. These in turn are related to the ages of the children involved. Attention is given to the frequency with which the victimized child had reported the incident(s) months to years before it was reported to an agency. In 50% of the cases the victimized children are under 12 years of age, and in 15% of the cases they are under 6 years of age. Suggestions are made regarding detection and preventive measures, particularly in the history-taking phase of the pediatrician-patient relationship and in vaginal physical findings.
Published: 1981
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49. Child Protective Services In Parental Mismanagement Of Diabetes

Author: Hendrika B. Cantwell
Subjects: medicine.medical_specialty, Colorado, Endocrinology, Diabetes and Metabolism, media_common.quotation_subject, Childhood diabetes, Child Welfare, Poison control, Health Professions (miscellaneous), Suicide prevention, Occupational safety and health, Neglect, Diabetes mellitus, Injury prevention, medicine, Humans, Child Abuse, Child, Psychiatry, media_common, business.industry, Human factors and ergonomics, medicine.disease, Diabetes Mellitus, Type 1, Female, Medical emergency, business
Abstract: Two cases of childhood diabetes are presented in which County Child Pro tective Services (CCPS) were re quested to intervene concerning medi cal neglect. The dynamics were quite different, but in both cases the child's diabetes was being neglectfully dealt with by the family. This resulted in one child being seriously emaciated with ascites and liver enlargement. The other child had been hospitalized eight times in the previous eleven months, each time presenting with severe keto acidosis. These cases are appropriate for referral to CCPS. Mismanagement of insulin dependent childhood dia betes may at times be more than "medical" neglect, becoming more like "Munchausen Syndrome by Proxy," or "Polle Syndrome. "
Published: 1984
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50. A study over a 5-year period of adjuvant chemotherapy after mastectomy for breast cancer

Author: J J, Fennelly, B, Cantwell, and M, Jones
Subjects: Postoperative Care, Methotrexate, Time Factors, Lymphatic Metastasis, Humans, Breast Neoplasms, Chlorambucil, Drug Therapy, Combination, Female, Fluorouracil, Mastectomy, Follow-Up Studies
Published: 1981

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