OBJECTIVE: A rare variant in TREM2 (p.R47H, rs75932628) has been consistently reported to increase the risk for Alzheimer disease (AD), while mixed evidence has been reported for association of the variant with other neurodegenerative diseases. Here, we investigated the frequency of the R47H variant in a diverse and well-characterized multicenter neurodegenerative disease cohort. METHODS: We examined the frequency of the R47H variant in a diverse neurodegenerative disease cohort, including a total of 3058 patients clinically diagnosed with AD, frontotemporal dementia spectrum syndromes, mild cognitive impairment, progressive supranuclear palsy syndrome, corticobasal syndrome, or amyotrophic lateral sclerosis and 5089 control subjects. RESULTS: We observed a significant association between the R47H variant and AD, while no association was observed with any other neurodegenerative disease included in this study. CONCLUSIONS: Our results support the consensus that the R47H variant is significantly associated with AD. However, we did not find evidence for association of the R47H variant with other neurodegenerative diseases.
OBJECTIVE: A rare variant in TREM2 (p.R47H, rs75932628) has been consistently reported to increase the risk for Alzheimer disease (AD), while mixed evidence has been reported for association of the variant with other neurodegenerative diseases. Here, we investigated the frequency of the R47H variant in a diverse and well-characterized multicenter neurodegenerative disease cohort. METHODS: We examined the frequency of the R47H variant in a diverse neurodegenerative disease cohort, including a total of 3058 patients clinically diagnosed with AD, frontotemporal dementia spectrum syndromes, mild cognitive impairment, progressive supranuclear palsy syndrome, corticobasal syndrome, or amyotrophic lateral sclerosis and 5089 control subjects. RESULTS: We observed a significant association between the R47H variant and AD, while no association was observed with any other neurodegenerative disease included in this study. CONCLUSIONS: Our results support the consensus that the R47H variant is significantly associated with AD. However, we did not find evidence for association of the R47H variant with other neurodegenerative diseases.
Authors: Guy M McKhann; David S Knopman; Howard Chertkow; Bradley T Hyman; Clifford R Jack; Claudia H Kawas; William E Klunk; Walter J Koroshetz; Jennifer J Manly; Richard Mayeux; Richard C Mohs; John C Morris; Martin N Rossor; Philip Scheltens; Maria C Carrillo; Bill Thies; Sandra Weintraub; Creighton H Phelps Journal: Alzheimers Dement Date: 2011-04-21 Impact factor: 21.566
Authors: M L Gorno-Tempini; A E Hillis; S Weintraub; A Kertesz; M Mendez; S F Cappa; J M Ogar; J D Rohrer; S Black; B F Boeve; F Manes; N F Dronkers; R Vandenberghe; K Rascovsky; K Patterson; B L Miller; D S Knopman; J R Hodges; M M Mesulam; M Grossman Journal: Neurology Date: 2011-02-16 Impact factor: 9.910
Authors: Melissa J Armstrong; Irene Litvan; Anthony E Lang; Thomas H Bak; Kailash P Bhatia; Barbara Borroni; Adam L Boxer; Dennis W Dickson; Murray Grossman; Mark Hallett; Keith A Josephs; Andrew Kertesz; Suzee E Lee; Bruce L Miller; Stephen G Reich; David E Riley; Eduardo Tolosa; Alexander I Tröster; Marie Vidailhet; William J Weiner Journal: Neurology Date: 2013-01-29 Impact factor: 9.910
Authors: Bruno A Benitez; Breanna Cooper; Pau Pastor; Sheng-Chih Jin; Elena Lorenzo; Sebastian Cervantes; Carlos Cruchaga Journal: Neurobiol Aging Date: 2013-02-05 Impact factor: 4.673
Authors: Katya Rascovsky; John R Hodges; David Knopman; Mario F Mendez; Joel H Kramer; John Neuhaus; John C van Swieten; Harro Seelaar; Elise G P Dopper; Chiadi U Onyike; Argye E Hillis; Keith A Josephs; Bradley F Boeve; Andrew Kertesz; William W Seeley; Katherine P Rankin; Julene K Johnson; Maria-Luisa Gorno-Tempini; Howard Rosen; Caroline E Prioleau-Latham; Albert Lee; Christopher M Kipps; Patricia Lillo; Olivier Piguet; Jonathan D Rohrer; Martin N Rossor; Jason D Warren; Nick C Fox; Douglas Galasko; David P Salmon; Sandra E Black; Marsel Mesulam; Sandra Weintraub; Brad C Dickerson; Janine Diehl-Schmid; Florence Pasquier; Vincent Deramecourt; Florence Lebert; Yolande Pijnenburg; Tiffany W Chow; Facundo Manes; Jordan Grafman; Stefano F Cappa; Morris Freedman; Murray Grossman; Bruce L Miller Journal: Brain Date: 2011-08-02 Impact factor: 13.501
Authors: Günter U Höglinger; Gesine Respondek; Maria Stamelou; Carolin Kurz; Keith A Josephs; Anthony E Lang; Brit Mollenhauer; Ulrich Müller; Christer Nilsson; Jennifer L Whitwell; Thomas Arzberger; Elisabet Englund; Ellen Gelpi; Armin Giese; David J Irwin; Wassilios G Meissner; Alexander Pantelyat; Alex Rajput; John C van Swieten; Claire Troakes; Angelo Antonini; Kailash P Bhatia; Yvette Bordelon; Yaroslau Compta; Jean-Christophe Corvol; Carlo Colosimo; Dennis W Dickson; Richard Dodel; Leslie Ferguson; Murray Grossman; Jan Kassubek; Florian Krismer; Johannes Levin; Stefan Lorenzl; Huw R Morris; Peter Nestor; Wolfgang H Oertel; Werner Poewe; Gil Rabinovici; James B Rowe; Gerard D Schellenberg; Klaus Seppi; Thilo van Eimeren; Gregor K Wenning; Adam L Boxer; Lawrence I Golbe; Irene Litvan Journal: Mov Disord Date: 2017-05-03 Impact factor: 10.338
Authors: Christina M Lill; Aina Rengmark; Lasse Pihlstrøm; Isabella Fogh; Aleksey Shatunov; Patrick M Sleiman; Li-San Wang; Tian Liu; Christina F Lassen; Esther Meissner; Panos Alexopoulos; Andrea Calvo; Adriano Chio; Nil Dizdar; Frank Faltraco; Lars Forsgren; Julia Kirchheiner; Alexander Kurz; Jan P Larsen; Maria Liebsch; Jan Linder; Karen E Morrison; Hans Nissbrandt; Markus Otto; Jens Pahnke; Amanda Partch; Gabriella Restagno; Dan Rujescu; Cathrin Schnack; Christopher E Shaw; Pamela J Shaw; Hayrettin Tumani; Ole-Bjørn Tysnes; Otto Valladares; Vincenzo Silani; Leonard H van den Berg; Wouter van Rheenen; Jan H Veldink; Ulman Lindenberger; Elisabeth Steinhagen-Thiessen; Stefan Teipel; Robert Perneczky; Hakon Hakonarson; Harald Hampel; Christine A F von Arnim; Jørgen H Olsen; Vivianna M Van Deerlin; Ammar Al-Chalabi; Mathias Toft; Beate Ritz; Lars Bertram Journal: Alzheimers Dement Date: 2015-04-30 Impact factor: 21.566
Authors: Rebecca Sims; Sven J van der Lee; Adam C Naj; Céline Bellenguez; Nandini Badarinarayan; Johanna Jakobsdottir; Brian W Kunkle; Anne Boland; Rachel Raybould; Joshua C Bis; Eden R Martin; Benjamin Grenier-Boley; Stefanie Heilmann-Heimbach; Vincent Chouraki; Amanda B Kuzma; Kristel Sleegers; Maria Vronskaya; Agustin Ruiz; Robert R Graham; Robert Olaso; Per Hoffmann; Megan L Grove; Badri N Vardarajan; Mikko Hiltunen; Markus M Nöthen; Charles C White; Kara L Hamilton-Nelson; Jacques Epelbaum; Wolfgang Maier; Seung-Hoan Choi; Gary W Beecham; Cécile Dulary; Stefan Herms; Albert V Smith; Cory C Funk; Céline Derbois; Andreas J Forstner; Shahzad Ahmad; Hongdong Li; Delphine Bacq; Denise Harold; Claudia L Satizabal; Otto Valladares; Alessio Squassina; Rhodri Thomas; Jennifer A Brody; Liming Qu; Pascual Sánchez-Juan; Taniesha Morgan; Frank J Wolters; Yi Zhao; Florentino Sanchez Garcia; Nicola Denning; Myriam Fornage; John Malamon; Maria Candida Deniz Naranjo; Elisa Majounie; Thomas H Mosley; Beth Dombroski; David Wallon; Michelle K Lupton; Josée Dupuis; Patrice Whitehead; Laura Fratiglioni; Christopher Medway; Xueqiu Jian; Shubhabrata Mukherjee; Lina Keller; Kristelle Brown; Honghuang Lin; Laura B Cantwell; Francesco Panza; Bernadette McGuinness; Sonia Moreno-Grau; Jeremy D Burgess; Vincenzo Solfrizzi; Petra Proitsi; Hieab H Adams; Mariet Allen; Davide Seripa; Pau Pastor; L Adrienne Cupples; Nathan D Price; Didier Hannequin; Ana Frank-García; Daniel Levy; Paramita Chakrabarty; Paolo Caffarra; Ina Giegling; Alexa S Beiser; Vilmantas Giedraitis; Harald Hampel; Melissa E Garcia; Xue Wang; Lars Lannfelt; Patrizia Mecocci; Gudny Eiriksdottir; Paul K Crane; Florence Pasquier; Virginia Boccardi; Isabel Henández; Robert C Barber; Martin Scherer; Lluis Tarraga; Perrie M Adams; Markus Leber; Yuning Chen; Marilyn S Albert; Steffi Riedel-Heller; Valur Emilsson; Duane Beekly; Anne Braae; Reinhold Schmidt; Deborah Blacker; Carlo Masullo; Helena Schmidt; Rachelle S Doody; Gianfranco Spalletta; W T Longstreth; Thomas J Fairchild; Paola Bossù; Oscar L Lopez; Matthew P Frosch; Eleonora Sacchinelli; Bernardino Ghetti; Qiong Yang; Ryan M Huebinger; Frank Jessen; Shuo Li; M Ilyas Kamboh; John Morris; Oscar Sotolongo-Grau; Mindy J Katz; Chris Corcoran; Melanie Dunstan; Amy Braddel; Charlene Thomas; Alun Meggy; Rachel Marshall; Amy Gerrish; Jade Chapman; Miquel Aguilar; Sarah Taylor; Matt Hill; Mònica Díez Fairén; Angela Hodges; Bruno Vellas; Hilkka Soininen; Iwona Kloszewska; Makrina Daniilidou; James Uphill; Yogen Patel; Joseph T Hughes; Jenny Lord; James Turton; Annette M Hartmann; Roberta Cecchetti; Chiara Fenoglio; Maria Serpente; Marina Arcaro; Carlo Caltagirone; Maria Donata Orfei; Antonio Ciaramella; Sabrina Pichler; Manuel Mayhaus; Wei Gu; Alberto Lleó; Juan Fortea; Rafael Blesa; Imelda S Barber; Keeley Brookes; Chiara Cupidi; Raffaele Giovanni Maletta; David Carrell; Sandro Sorbi; Susanne Moebus; Maria Urbano; Alberto Pilotto; Johannes Kornhuber; Paolo Bosco; Stephen Todd; David Craig; Janet Johnston; Michael Gill; Brian Lawlor; Aoibhinn Lynch; Nick C Fox; John Hardy; Roger L Albin; Liana G Apostolova; Steven E Arnold; Sanjay Asthana; Craig S Atwood; Clinton T Baldwin; Lisa L Barnes; Sandra Barral; Thomas G Beach; James T Becker; Eileen H Bigio; Thomas D Bird; Bradley F Boeve; James D Bowen; Adam Boxer; James R Burke; Jeffrey M Burns; Joseph D Buxbaum; Nigel J Cairns; Chuanhai Cao; Chris S Carlson; Cynthia M Carlsson; Regina M Carney; Minerva M Carrasquillo; Steven L Carroll; Carolina Ceballos Diaz; Helena C Chui; David G Clark; David H Cribbs; Elizabeth A Crocco; Charles DeCarli; Malcolm Dick; Ranjan Duara; Denis A Evans; Kelley M Faber; Kenneth B Fallon; David W Fardo; Martin R Farlow; Steven Ferris; Tatiana M Foroud; Douglas R Galasko; Marla Gearing; Daniel H Geschwind; John R Gilbert; Neill R Graff-Radford; Robert C Green; John H Growdon; Ronald L Hamilton; Lindy E Harrell; Lawrence S Honig; Matthew J Huentelman; Christine M Hulette; Bradley T Hyman; Gail P Jarvik; Erin Abner; Lee-Way Jin; Gyungah Jun; Anna Karydas; Jeffrey A Kaye; Ronald Kim; Neil W Kowall; Joel H Kramer; Frank M LaFerla; James J Lah; James B Leverenz; Allan I Levey; Ge Li; Andrew P Lieberman; Kathryn L Lunetta; Constantine G Lyketsos; Daniel C Marson; 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; John C Morris; Jill R Murrell; Amanda J Myers; Sid O'Bryant; John M Olichney; Vernon S Pankratz; Joseph E Parisi; Henry L Paulson; William Perry; Elaine Peskind; Aimee Pierce; Wayne W Poon; Huntington Potter; Joseph F Quinn; Ashok Raj; Murray Raskind; Barry Reisberg; Christiane Reitz; John M Ringman; Erik D Roberson; Ekaterina Rogaeva; Howard J Rosen; Roger N Rosenberg; Mark A Sager; Andrew J Saykin; Julie A Schneider; Lon S Schneider; William W Seeley; Amanda G Smith; Joshua A Sonnen; Salvatore Spina; Robert A Stern; Russell H Swerdlow; Rudolph E Tanzi; Tricia A Thornton-Wells; John Q Trojanowski; Juan C Troncoso; Vivianna M Van Deerlin; Linda J Van Eldik; Harry V Vinters; Jean Paul Vonsattel; Sandra Weintraub; Kathleen A Welsh-Bohmer; Kirk C Wilhelmsen; Jennifer Williamson; Thomas S Wingo; Randall L Woltjer; Clinton B Wright; Chang-En Yu; Lei Yu; Fabienne Garzia; Feroze Golamaully; Gislain Septier; Sebastien Engelborghs; Rik Vandenberghe; Peter P De Deyn; Carmen Muñoz Fernadez; Yoland Aladro Benito; Hakan Thonberg; Charlotte Forsell; Lena Lilius; Anne Kinhult-Stählbom; Lena Kilander; RoseMarie Brundin; Letizia Concari; Seppo Helisalmi; Anne Maria Koivisto; Annakaisa Haapasalo; Vincent Dermecourt; Nathalie Fievet; Olivier Hanon; Carole Dufouil; Alexis Brice; Karen Ritchie; Bruno Dubois; Jayanadra J Himali; C Dirk Keene; JoAnn Tschanz; Annette L Fitzpatrick; Walter A Kukull; Maria Norton; Thor Aspelund; Eric B Larson; Ron Munger; Jerome I Rotter; Richard B Lipton; María J Bullido; Albert Hofman; Thomas J Montine; Eliecer Coto; Eric Boerwinkle; Ronald C Petersen; Victoria Alvarez; Fernando Rivadeneira; Eric M Reiman; Maura Gallo; Christopher J O'Donnell; Joan S Reisch; Amalia Cecilia Bruni; Donald R Royall; Martin Dichgans; Mary Sano; Daniela Galimberti; Peter St George-Hyslop; Elio Scarpini; Debby W Tsuang; Michelangelo Mancuso; Ubaldo Bonuccelli; Ashley R Winslow; Antonio Daniele; Chuang-Kuo Wu; Oliver Peters; Benedetta Nacmias; Matthias Riemenschneider; Reinhard Heun; Carol Brayne; David C Rubinsztein; Jose Bras; Rita Guerreiro; Ammar Al-Chalabi; Christopher E Shaw; John Collinge; David Mann; Magda Tsolaki; Jordi Clarimón; Rebecca Sussams; Simon Lovestone; Michael C O'Donovan; Michael J Owen; Timothy W Behrens; Simon Mead; Alison M Goate; Andre G Uitterlinden; Clive Holmes; Carlos Cruchaga; Martin Ingelsson; David A Bennett; John Powell; Todd E Golde; Caroline Graff; Philip L De Jager; Kevin Morgan; Nilufer Ertekin-Taner; Onofre Combarros; Bruce M Psaty; Peter Passmore; Steven G Younkin; Claudine Berr; Vilmundur Gudnason; Dan Rujescu; Dennis W Dickson; Jean-François Dartigues; Anita L DeStefano; Sara Ortega-Cubero; Hakon Hakonarson; Dominique Campion; Merce Boada; John Keoni Kauwe; Lindsay A Farrer; Christine Van Broeckhoven; M Arfan Ikram; Lesley Jones; Jonathan L Haines; Christophe Tzourio; Lenore J Launer; Valentina Escott-Price; Richard Mayeux; Jean-François Deleuze; Najaf Amin; Peter A Holmans; Margaret A Pericak-Vance; Philippe Amouyel; Cornelia M van Duijn; Alfredo Ramirez; Li-San Wang; Jean-Charles Lambert; Sudha Seshadri; Julie Williams; Gerard D Schellenberg Journal: Nat Genet Date: 2017-07-17 Impact factor: 41.307
Authors: J C Lambert; C A Ibrahim-Verbaas; D Harold; A C Naj; R Sims; C Bellenguez; A L DeStafano; J C Bis; G W Beecham; B Grenier-Boley; G Russo; T A Thorton-Wells; N Jones; A V Smith; V Chouraki; C Thomas; M A Ikram; D Zelenika; B N Vardarajan; Y Kamatani; C F Lin; A Gerrish; H Schmidt; B Kunkle; M L Dunstan; A Ruiz; M T Bihoreau; S H Choi; C Reitz; F Pasquier; C Cruchaga; D Craig; N Amin; C Berr; O L Lopez; P L De Jager; V Deramecourt; J A Johnston; D Evans; S Lovestone; L Letenneur; F J Morón; D C Rubinsztein; G Eiriksdottir; K Sleegers; A M Goate; N Fiévet; M W Huentelman; M Gill; K Brown; M I Kamboh; L Keller; P Barberger-Gateau; B McGuiness; E B Larson; R Green; A J Myers; C Dufouil; S Todd; D Wallon; S Love; E Rogaeva; J Gallacher; P St George-Hyslop; J Clarimon; A Lleo; A Bayer; D W Tsuang; L Yu; M Tsolaki; P Bossù; G Spalletta; P Proitsi; J Collinge; S Sorbi; F Sanchez-Garcia; N C Fox; J Hardy; M C Deniz Naranjo; P Bosco; R Clarke; C Brayne; D Galimberti; M Mancuso; F Matthews; S Moebus; P Mecocci; M Del Zompo; W Maier; H Hampel; A Pilotto; M Bullido; F Panza; P Caffarra; B Nacmias; J R Gilbert; M Mayhaus; L Lannefelt; H Hakonarson; S Pichler; M M Carrasquillo; M Ingelsson; D Beekly; V Alvarez; F Zou; O Valladares; S G Younkin; E Coto; K L Hamilton-Nelson; W Gu; C Razquin; P Pastor; I Mateo; M J Owen; K M Faber; P V Jonsson; O Combarros; M C O'Donovan; L B Cantwell; H Soininen; D Blacker; S Mead; T H Mosley; D A Bennett; T B Harris; L Fratiglioni; C Holmes; R F de Bruijn; P Passmore; T J Montine; K Bettens; J I Rotter; A Brice; K Morgan; T M Foroud; W A Kukull; D Hannequin; J F Powell; M A Nalls; K Ritchie; K L Lunetta; J S Kauwe; E Boerwinkle; M Riemenschneider; M Boada; M Hiltuenen; E R Martin; R Schmidt; D Rujescu; L S Wang; J F Dartigues; R Mayeux; C Tzourio; A Hofman; M M Nöthen; C Graff; B M Psaty; L Jones; J L Haines; P A Holmans; M Lathrop; M A Pericak-Vance; L J Launer; L A Farrer; C M van Duijn; C Van Broeckhoven; V Moskvina; S Seshadri; J Williams; G D Schellenberg; P Amouyel Journal: Nat Genet Date: 2013-10-27 Impact factor: 38.330
Authors: Rita Guerreiro; Aleksandra Wojtas; Jose Bras; Minerva Carrasquillo; Ekaterina Rogaeva; Elisa Majounie; Carlos Cruchaga; Celeste Sassi; John S K Kauwe; Steven Younkin; Lilinaz Hazrati; John Collinge; Jennifer Pocock; Tammaryn Lashley; Julie Williams; Jean-Charles Lambert; Philippe Amouyel; Alison Goate; Rosa Rademakers; Kevin Morgan; John Powell; Peter St George-Hyslop; Andrew Singleton; John Hardy Journal: N Engl J Med Date: 2012-11-14 Impact factor: 91.245