OBJECTIVE: To investigate whether genome-wide association study (GWAS)-validated and GWAS-promising candidate loci influence magnetic resonance imaging measures and clinical Alzheimer's disease (AD) status. DESIGN: Multicenter case-control study of genetic and neuroimaging data from the Alzheimer's Disease Neuroimaging Initiative. SETTING: Multicenter GWAS. Patients A total of 168 individuals with probable AD, 357 with mild cognitive impairment, and 215 cognitively normal control individuals recruited from more than 50 Alzheimer's Disease Neuroimaging Initiative centers in the United States and Canada. All study participants had APOE and genome-wide genetic data available. MAIN OUTCOME MEASURES: We investigated the influence of GWAS-validated and GWAS-promising novel AD loci on hippocampal volume, amygdala volume, white matter lesion volume, entorhinal cortex thickness, parahippocampal gyrus thickness, and temporal pole cortex thickness. RESULTS: Markers at the APOE locus were associated with all phenotypes except white matter lesion volume (all false discovery rate-corrected P values < .001). Novel and established AD loci identified by prior GWASs showed a significant cumulative score-based effect (false discovery rate P = .04) on all analyzed neuroimaging measures. The GWAS-validated variants at the CR1 and PICALM loci and markers at 2 novel loci (BIN1 and CNTN5) showed association with multiple magnetic resonance imaging characteristics (false discovery rate P < .05). CONCLUSIONS: Loci associated with AD also influence neuroimaging correlates of this disease. Furthermore, neuroimaging analysis identified 2 additional loci of high interest for further study.
OBJECTIVE: To investigate whether genome-wide association study (GWAS)-validated and GWAS-promising candidate loci influence magnetic resonance imaging measures and clinical Alzheimer's disease (AD) status. DESIGN: Multicenter case-control study of genetic and neuroimaging data from the Alzheimer's Disease Neuroimaging Initiative. SETTING: Multicenter GWAS. Patients A total of 168 individuals with probable AD, 357 with mild cognitive impairment, and 215 cognitively normal control individuals recruited from more than 50 Alzheimer's Disease Neuroimaging Initiative centers in the United States and Canada. All study participants had APOE and genome-wide genetic data available. MAIN OUTCOME MEASURES: We investigated the influence of GWAS-validated and GWAS-promising novel AD loci on hippocampal volume, amygdala volume, white matter lesion volume, entorhinal cortex thickness, parahippocampal gyrus thickness, and temporal pole cortex thickness. RESULTS: Markers at the APOE locus were associated with all phenotypes except white matter lesion volume (all false discovery rate-corrected P values < .001). Novel and established AD loci identified by prior GWASs showed a significant cumulative score-based effect (false discovery rate P = .04) on all analyzed neuroimaging measures. The GWAS-validated variants at the CR1 and PICALM loci and markers at 2 novel loci (BIN1 and CNTN5) showed association with multiple magnetic resonance imaging characteristics (false discovery rate P < .05). CONCLUSIONS: Loci associated with AD also influence neuroimaging correlates of this disease. Furthermore, neuroimaging analysis identified 2 additional loci of high interest for further study.
Authors: Steven G Potkin; Guia Guffanti; Anita Lakatos; Jessica A Turner; Frithjof Kruggel; James H Fallon; Andrew J Saykin; Alessandro Orro; Sara Lupoli; Erika Salvi; Michael Weiner; Fabio Macciardi Journal: PLoS One Date: 2009-08-07 Impact factor: 3.240
Authors: W J P Henneman; J D Sluimer; J Barnes; W M van der Flier; I C Sluimer; N C Fox; P Scheltens; H Vrenken; F Barkhof Journal: Neurology Date: 2009-03-17 Impact factor: 9.910
Authors: R S Desikan; H J Cabral; B Fischl; C R G Guttmann; D Blacker; B T Hyman; M S Albert; R J Killiany Journal: AJNR Am J Neuroradiol Date: 2008-12-26 Impact factor: 3.825
Authors: Sekar Kathiresan; Benjamin F Voight; Shaun Purcell; Kiran Musunuru; Diego Ardissino; Pier M Mannucci; Sonia Anand; James C Engert; Nilesh J Samani; Heribert Schunkert; Jeanette Erdmann; Muredach P Reilly; Daniel J Rader; Thomas Morgan; John A Spertus; Monika Stoll; Domenico Girelli; Pascal P McKeown; Chris C Patterson; David S Siscovick; Christopher J O'Donnell; Roberto Elosua; Leena Peltonen; Veikko Salomaa; Stephen M Schwartz; Olle Melander; David Altshuler; Diego Ardissino; Pier Angelica Merlini; Carlo Berzuini; Luisa Bernardinelli; Flora Peyvandi; Marco Tubaro; Patrizia Celli; Maurizio Ferrario; Raffaela Fetiveau; Nicola Marziliano; Giorgio Casari; Michele Galli; Flavio Ribichini; Marco Rossi; Francesco Bernardi; Pietro Zonzin; Alberto Piazza; Pier M Mannucci; Stephen M Schwartz; David S Siscovick; Jean Yee; Yechiel Friedlander; Roberto Elosua; Jaume Marrugat; Gavin Lucas; Isaac Subirana; Joan Sala; Rafael Ramos; Sekar Kathiresan; James B Meigs; Gordon Williams; David M Nathan; Calum A MacRae; Christopher J O'Donnell; Veikko Salomaa; Aki S Havulinna; Leena Peltonen; Olle Melander; Goran Berglund; Benjamin F Voight; Sekar Kathiresan; Joel N Hirschhorn; Rosanna Asselta; Stefano Duga; Marta Spreafico; Kiran Musunuru; Mark J Daly; Shaun Purcell; Benjamin F Voight; Shaun Purcell; James Nemesh; Joshua M Korn; Steven A McCarroll; Stephen M Schwartz; Jean Yee; Sekar Kathiresan; Gavin Lucas; Isaac Subirana; Roberto Elosua; Aarti Surti; Candace Guiducci; Lauren Gianniny; Daniel Mirel; Melissa Parkin; Noel Burtt; Stacey B Gabriel; Nilesh J Samani; John R Thompson; Peter S Braund; Benjamin J Wright; Anthony J Balmforth; Stephen G Ball; Alistair S Hall; Heribert Schunkert; Jeanette Erdmann; Patrick Linsel-Nitschke; Wolfgang Lieb; Andreas Ziegler; Inke König; Christian Hengstenberg; Marcus Fischer; Klaus Stark; Anika Grosshennig; Michael Preuss; H-Erich Wichmann; Stefan Schreiber; Heribert Schunkert; Nilesh J Samani; Jeanette Erdmann; Willem Ouwehand; Christian Hengstenberg; Panos Deloukas; Michael Scholz; Francois Cambien; Muredach P Reilly; Mingyao Li; Zhen Chen; Robert Wilensky; William Matthai; Atif Qasim; Hakon H Hakonarson; Joe Devaney; Mary-Susan Burnett; Augusto D Pichard; Kenneth M Kent; Lowell Satler; Joseph M Lindsay; Ron Waksman; Christopher W Knouff; Dawn M Waterworth; Max C Walker; Vincent Mooser; Stephen E Epstein; Daniel J Rader; Thomas Scheffold; Klaus Berger; Monika Stoll; Andreas Huge; Domenico Girelli; Nicola Martinelli; Oliviero Olivieri; Roberto Corrocher; Thomas Morgan; John A Spertus; Pascal McKeown; Chris C Patterson; Heribert Schunkert; Erdmann Erdmann; Patrick Linsel-Nitschke; Wolfgang Lieb; Andreas Ziegler; Inke R König; Christian Hengstenberg; Marcus Fischer; Klaus Stark; Anika Grosshennig; Michael Preuss; H-Erich Wichmann; Stefan Schreiber; Hilma Hólm; Gudmar Thorleifsson; Unnur Thorsteinsdottir; Kari Stefansson; James C Engert; Ron Do; Changchun Xie; Sonia Anand; Sekar Kathiresan; Diego Ardissino; Pier M Mannucci; David Siscovick; Christopher J O'Donnell; Nilesh J Samani; Olle Melander; Roberto Elosua; Leena Peltonen; Veikko Salomaa; Stephen M Schwartz; David Altshuler Journal: Nat Genet Date: 2009-02-08 Impact factor: 38.330
Authors: Sekar Kathiresan; Cristen J Willer; Gina M Peloso; Serkalem Demissie; Kiran Musunuru; Eric E Schadt; Lee Kaplan; Derrick Bennett; Yun Li; Toshiko Tanaka; Benjamin F Voight; Lori L Bonnycastle; Anne U Jackson; Gabriel Crawford; Aarti Surti; Candace Guiducci; Noel P Burtt; Sarah Parish; Robert Clarke; Diana Zelenika; Kari A Kubalanza; Mario A Morken; Laura J Scott; Heather M Stringham; Pilar Galan; Amy J Swift; Johanna Kuusisto; Richard N Bergman; Jouko Sundvall; Markku Laakso; Luigi Ferrucci; Paul Scheet; Serena Sanna; Manuela Uda; Qiong Yang; Kathryn L Lunetta; Josée Dupuis; Paul I W de Bakker; Christopher J O'Donnell; John C Chambers; Jaspal S Kooner; Serge Hercberg; Pierre Meneton; Edward G Lakatta; Angelo Scuteri; David Schlessinger; Jaakko Tuomilehto; Francis S Collins; Leif Groop; David Altshuler; Rory Collins; G Mark Lathrop; Olle Melander; Veikko Salomaa; Leena Peltonen; Marju Orho-Melander; Jose M Ordovas; Michael Boehnke; Gonçalo R Abecasis; Karen L Mohlke; L Adrienne Cupples Journal: Nat Genet Date: 2008-12-07 Impact factor: 38.330
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Authors: Michael W Weiner; Dallas P Veitch; Paul S Aisen; Laurel A Beckett; Nigel J Cairns; Robert C Green; Danielle Harvey; Clifford R Jack; William Jagust; Enchi Liu; John C Morris; Ronald C Petersen; Andrew J Saykin; Mark E Schmidt; Leslie Shaw; Judith A Siuciak; Holly Soares; Arthur W Toga; John Q Trojanowski Journal: Alzheimers Dement Date: 2011-11-02 Impact factor: 21.566
Authors: Mark W Logue; Matthew Schu; Badri N Vardarajan; Jacki Buros; Robert C Green; Rodney C P Go; Patrick Griffith; Thomas O Obisesan; Rhonna Shatz; Amy Borenstein; L Adrienne Cupples; Kathryn L Lunetta; M Daniele Fallin; Clinton T Baldwin; Lindsay A Farrer Journal: Arch Neurol Date: 2011-12
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Authors: S Barral; T Bird; A Goate; M R Farlow; R Diaz-Arrastia; D A Bennett; N Graff-Radford; B F Boeve; R A Sweet; Y Stern; R S Wilson; T Foroud; J Ott; R Mayeux Journal: Neurology Date: 2012-04-25 Impact factor: 9.910
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