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Neurobiol Aging. 2012 Jul;33(7):1486.e9-15. doi: 10.1016/j.neurobiolaging.2011.02.008. Epub 2011 Apr 3.

Using CSF biomarkers to replicate genetic associations in Alzheimer's disease.

Collaborators (1209)

Abdi H, Abdul Hadi N, Abdulkadir A, Abdullah A, Achuthan A, Adluru N, Aggarwal N, Aghajanian J, Agyemang A, Ahdidan J, Ahmad D, Ahmed F, Ahmed S, Ahmed F, Akbarifar R, Akhondi-Asl A, Aksu Y, Alcauter S, Alexander D, Alin A, Alshuft H, Alvarez-Linera J, Amin-Mansour A, Anderson J, Anderson D, Andorn A, Andrews KA, Ang A, Angersbach S, Ansarian R, Abhishek AM, Appannah A, Arfanakis K, Arif M, Armentrout S, Arrighi M, Arumughababu SV, Arunagiri V, Ashe-McNalley C, Ashford W, Le Page A, Avants B, Aviv R, Avula R, Ayache N, Ayan-Oshodi M, Ayhan M, Sumana BV, Bach Cuadra M, Bagepally B, Bahar Fuchs A, Baird G, Baker S, Baker J, Bakker A, Baladandayuthapani V, Barbash S, Barillot C, Barker W, Bartlett J, Bartley M, Baruchin A, Battaglini I, Bauer C, Bayley P, Becker J, Beckett L, Bednar M, Bedner A, Beg MF, Bekris L, Belaroussi B, Belloch V, Belmokhtar N, Ben Ahmed O, Bender JD, Bendib MM, Benois-Pineau J, Bhagchandani S, Bienkowska K, Biffi A, Bilgin G, Billing B, Bishop C, Bittner D, Björnsdotter M, Black S, Bloss C, Blunck Y, Bocti C, Bohorquez A, Bokde A, Boone J, Boord P, Boot B, Borrie M, Boudousq V, Bourgeat P, Bouttout H, Bowman D, Bowman G, Boxer A, Bozoki A, Bracard S, Braskie M, Breitner J, Bresell A, Brewer J, Brickhouse M, Brickman A, Britschgi M, Broadbent S, Brock B, Brown M, Buchsbaum M, Buerger K, Bunce D, Burnham S, Burns J, Burzykowski T, Butler T, Cabeza R, Cabral G, Caffery T, Cai Z, Callhoff J, Calvini P, Campbell N, Carbotti A, Carle A, Carmasin J, Carmasin J, Carpenter J, Carvalho J, Casanova R, Casey A, Cash D, Cash D, Cataldo R, Cella M, Chadaga A, Chakravarty M, Chang I, Chao L, Chaovalitwongse WA, Charil A, Chatterjee S, Che-Wei C, Chen K, Chen G, Chen S, Chen R, Chen IJ, Chen JT, Chen C, Chen J, Chen Q, Chen H, Cheng WC, Cheng X, Cheng B, Cherkas Y, Chertkow H, Chiang G, Chiao P, chibane MB, Chida N, Chin S, Ching C, Chisholm J, Cho SS, Cho C, Choe J, Choubey S, Chowbina S, Ciocia G, Clark D, Clarkson M, Clerc S, Climer S, Clunie D, Coen M, Coimbra A, Compton D, Conover J, Coubard O, Coulin S, Coulson E, Cover KS, Crans G, Crawford K, Croop R, Crum W, Cui Y, Da L, Dai Y, Daiello L, Daiello L, Darkner S, Darnell R, Davatzikos C, DavidPrakash B, Davidson C, Davis M, de Bruijne M, DeCarli C, Decker S, DeDuck K, Dehghan H, Della Rosa PA, DeOrchis V, Dépy Carron D, Desikan R, Desjardins B, deToledo-Morrell L, Devanand D, Devanarayan V, Devier D, Devous M, Di X, Di J, Diaz-Arrastia R, Diciotti S, Dickerson B, Dickie DA, Dickinson P, Dill V, Ding X, Dinov I, Dobosh B, Dobson H, Dodge H, Dolman A, Dolmo BC, Dong W, Donohue M, Dore V, Dorflinger E, Dowling M, Dowling M, Dragicevic N, Dricot L, Duchesne S, Duff K, Dukart J, Durazzo T, Dutta J, DWors R, Egefjord L, Elcoroaristizabal X, Emahazion T, Emahazion T, Endres C, Epstein N, Ereshefsky L, Eskildsen S, Espinosa A, Esposito M, Ewers M, Ewers M, Falcone G, Fan J, Fan Y, Fan Z, Fang Z, Farahibozorg S, Farahmandpoor Z, Farb N, Fardo D, Farias S, Farnum M, Farrer L, Fatke B, Faux N, Favilla S, Fazlollahi A, Feldman B, Félix Z, Fennema-Notestine C, Fernandes M, Fernandez S, Fernandez E, Ferrari R, Ferrer E, Fetterman B, Figurski M, Fillit H, Finch S, Finger E, Fiot JB, Flenniken D, Fletcher E, Flores C, Flynn Longmire C, Focke N, Forsythe A, Fox A, Fox A, Foxhall S, Franko E, Frederick B, Freeman R, Freire R, Friedrich CM, Friesenhahn M, Frisoni G, Fritzsche K, Fujiwara K, Fullerton T, Gaffour Y, Galbraith S, Galvin B, Gamst A, Gan K, Gao S, Garcia G, Garg G, Gaser C, Gastineau E, Gattaz W, Gaubert M, Gaudreau A, Gauthier S, Gavidia G, Gemme G, Geraci J, Gholipour F, Ghosh S, Ghosh D, Gieschke R, Gill R, Gillespie W, Gispert JD, Gitelman D, Gkontra X, Gleason C, Glymour MM, Godbey M, Gold B, Goldberg T, Goldman J, Gomar J, Gonzalez-Beltran A, Gore C, Gorriz JM, Goto M, Gou JI, Gradkowski W, Grasela T, Gray K, Gregory E, Greicius M, Grill J, Grolmusz V, Gross A, Gross A, Grydeland H, Guignot I, Guillaume B, Guilloux F, Guo LH, Guo H, Gupta V, Gurney G, Guyot J, Haas M, Habeck C, Habte F, Haight T, Hajaj C, Hajiesmaeili M, Hajjar I, Hammarstrom P, Han Z, Han D, Hanna Y, Hanna-Pladdy B, Hao Y, Hardy P, Harrison J, Harvey D, Harvey D, Hassanzadeh O, Hayashi T, Haynes JD, He Y, He H, Head D, Heckemann R, Heegaard N, Heidarieh SM, Heidebrink J, Hellyer P, Helwig M, Henderson D, Herholz K, Hess C, Hill S, Hisaka A, Ho Ming AY, Hobart J, Hochstetler H, Hofer S, Hoffman J, Holder D, Hollingworth P, Holmes R, Hong L, Hong H, Hong Q, Honigberg L, Hoogenraad F, Hope T, Hot T, Hsieh H, Hsu A, Hu M, Hu W, Hu X, Hu C, Hua WY, Huang X, Huang CJ, Huang Y, Huang J, Huang Z, Huentelman M, Huppertz HJ, Hurt S, Hussain M, Hutchins J, Hwang S, Hyun J, Ifeachor E, Iglesias M, Ikari Y, Ikonomidou V, Iman A, Imani F, Inlow M, Inoue L, Insel P, Irizarry M, Ishibashi T, Ishii K, Ito K, Iwatsubo T, Jacks A, Jacobson M, Jacqmin P, Jaeger M, Jaeger P, Jagger R, Jagust W, Janousova E, Jara H, Jedynak B, Jefferson A, Jenq J, Jiang T, Jiang C, Jiao Y, Jiaolong Q, Jin K, Johnson S, Johnson J, Johnson K, Jones R, Jones G, Jones M, Joshi R, Joshi S, Joshi A, Jouvent E, Juengling F, Jung W, Junjie Z, Muthamma KG, Kabilan M, Kairui Z, Kaludov N, Kam HJ, Kamakura V, Kamer A, Kanakaraj S, Kanchev V, Kaneko T, Kaneta T, Kang JH, Kang H, Kang J, Karantzoulis S, Katz I, Kaushik SS, Kauwe J, Kauwe J, Kawashima S, Kaye E, Kazemi S, Ke H, Kelleher T, Kennedy R, Keogh B, Kerchner G, Kerr D, Keshava N, Khalil A, Khondker Z, Khondker Z, Kiddle S, Kihara T, Killeen N, Killiany R, Kim JH, Kim JH, Kim D, Kim D, Kimberg D, King R, Kingery L, Kirby J, Kirsch W, Klein G, Klimas M, Kline R, Klopfenstein E, Koen J, Koenig L, Koikkalainen J, Kokomoor A, Kong X, Kong X, Koppel J, Korolev I, Kotamarti RM, Krahnke T, Krams M, Kraybill M, Kuceyeski A, Kuceyeski A, Kumar V, Kumar Roy P, Kuo J, Kyrtsos CR, Labib V, Labrish C, Lai S, Lakatos A, Lalonde F, Lam SC, Landau S, Lane B, Langbaum J, Langford D, Lanius V, Lasch S, Latella M, Lau H, Leatherday C, Lebedev A, Lee S, Lee Ja, Lee D, Lee G, Legal S, Lei H, Lemaitre H, Lenfant P, Leonards U, Leong J, Leoutsakos JM, Leung YY, Leung K, Levey A, Li M, Li L, Li J, Li Y, Li M, Li J, Li Y, Li Y, Li J, Li W, Li X, Li R, Li Q, Liang K, Liang P, Liao S, Liao W, Liaquat S, Liaw C, Liberman G, Lilley P, Lim JS, Lin F, Lin X, Linninger A, Liu S, Liu X, Liu G, Liu Y, Liu Y, Liu T, Liu L, Liu M, Liu T, Liu W, Liu C, Liu T, Liu Y, Liu X, Liu T, Liu H, Liu D, Liu X, Liu Y, Llido J, Lo R, Lobach I, Lobanov V, Lockhart A, Long X, Long Z, Long M, Looi J, Lu Y, Lu PH, Lu H, Lucena N, Luis J, Lukas C, Lukic A, Luo X, Luo S, Luo L, Luo W, Luo X, Ma SL, Ma SM, Mackin S, Mada M, Madabhushi A, Madeira S, Magland J, Mahanta MS, Maikusa N, Maldjian J, Malpas C, Mandal I, Mandal P, Mang A, Mangin JF, Manjon J, Mantri N, Manzour A, Marcus D, Margolin R, Marrett S, Marshall G, Martinez Gonzalez A, Martinez Torteya A, Martins R, Mather M, Mathis C, Matoug S, Mattei P, Matthews D, Mattis P, McCarroll S, McConathy J, McDonald C, McEvoy L, McGeown W, McGinnis S, McGonigle J, Randal McIntosh A, McIntyre J, McLaren D, McMillan C, McQuail J, Meadowcroft M, Meda S, Melie-Garcia L, Melrose R, Mendelson A, Mendez M, Menendez E, Meng M, Meng M, Meredith J, Meyer M, Meyer C, Mez J, Mickael G, Mikula M, Miller M, Millikin C, Mintun M, Mitchell M, Mitsis E, Mon A, Moore D, Morabito FC, Birgani PM, Moratal D, Morimoto B, Morris J, Morris J, Mortamet B, Moscato P, Mourao-Miranda J, Mueller S, Mueller K, Mukherjee S, Mukund N, Mulder E, Mungas D, Munir K, Murayama S, Murphy K, Sairam N, Nagata K, Nair A, Narayana P, Nasrabadi S, Nativio R, Nazeri A, Nejad L, Nekooei S, Nemeth I, Nencka A, Nettiksimmons J, Neu S, Ng YB, Nguyen N, Nguyen H, Nichols T, Niecko T, Nielsen C, Niethammer M, Nishio T, Noda A, Nordstrom M, Noshad S, Notomi K, Novak N, Nutakki GC, O'Charoen S, Obisesan T, Oh J, Okonkwo O, Rikkert MO, Oliveira J, Oliveira A, Oliver R, Olmos S, Oltra J, Ong R, Osadebey M, Osadebey M, Ostrowitzki S, Ovando Vazquez CM, Overholser R, Anishiya P, Chitra PK, Pa J, Pa J, Palanisamy P, Pan S, Pan G, Pan Z, Pande Y, Pardo J, Pardoe H, Park H, Park L, Park J, Park S, Parker C, Patel Y, Patil M, Patil A, Pawlak M, Payoux P, Pennec X, Pereira F, Perlbarg V, Perneczky R, Peters F, Petitti D, Petrella J, Petrou M, Peyrat JM, Pham Ngoc PT, Phillips J, Phillips N, Pian WT, Pierson R, Piovezan M, Pipitone J, Pirraglia E, Planes X, Podhorski A, Poirier J, Pomara N, Popov V, Poppenkv J, Potkin S, Potter G, Poulin S, Prastawa M, Prince J, Priya K, Pruessner J, Qiu W, Qu A, Qualls CD, Quarg P, Quinlan J, Rabbia M, Rajagovindan R, Rajeesh R, Ramadubramani V, Ramage A, Ramirez A, Randolph C, Rao A, Rao H, Reed B, Reid A, Reilhac A, Reiner P, Reinsberger C, Reiss P, Ren J, Retico A, Rhatigan L, Rhinn H, Rhoades E, Ribbens A, Richard E, Richards J, Richter M, Riddle W, Ridgway G, Ringman J, Rizk-Jackson A, Rizzi M, Rodriguez N, Rodriguez L, Rodriguez-Vieitez E, Rogalski E, Rojas Balderrama J, Rokicki J, Romero K, Rosand J, Rosen O, Rostant O, Rousseau F, Roy M, Rubright J, Rucinski M, Ruiz A, Rulseh A, Rusinek H, Ryan L, Sabuncu M, Saculva M, Sahuquillo J, Said Y, Saito N, Sakata M, Salama M, Salazar D, Saman S, Sanchez L, Sanders E, Sankar T, Santhamma S, Sarwinda D, Sasaki T, Sasaya T, Sato H, Sattlecker M, Savio A, Saykin A, Scanlon B, Scharre D, Schegerin M, Schmand B, Schmansky N, Schmidt-Wilcke T, Schneider B, Schott J, Schramm H, Schuerch M, Schultz T, Schwartz E, Schwartz P, Schwarz J, Schwarz A, Schweizer T, Selnes P, Sembritzki K, Senjem M, Sfikas G, Sghedoni R, Shah JH, Shahbaba B, Shams S, Shankle W, Shattuck D, Shaw L, Shen J, Shen Q, Shen J, Shen Q, Shera D, Sherer E, Sherman M, Sherva R, Shi J, Shi Y, Shi Y, Shi F, Shilaskar S, Shinohara R, Shokouhi S, Shulman J, Sideris K, Siegel R, Silveira M, Silverman D, Simak A, Simmons A, Simoes R, Simon H, Simon A, Simonson A, Simpson D, Simpson I, Singh L, Singh N, Sinha N, Siuciak J, Sjögren N, Skinner J, Skudlarski P, Smith M, Smith C, Snyder P, Soares H, 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Yang Z, Yang JJ, Yang HD, Yang E, Yang CY, Yang E, Yang H, Yang W, Yassa M, Yatsubo S, Yavorsky C, Ye BS, Yee L, Yokoyama J, Yokoyama T, Young S, Younhyun J, Yu CQ, Yu P, Yuan Y, Yuen B, Yushkevich P, Zaborszky L, Zagorodnov V, Zahodne L, Zarei M, Zeimpekis K, Zeitzer J, Zelinski E, Zeskind B, Zhan S, Zhang Z, Zhang T, Zhang J, Zhang Z, Zhang X, Zhang Y, Zhang D, Zhang L, Zhang K, Zhang L, Zhang M, Zhang P, Zhao P, Zhao X, Zhijun Y, Zhou L, Zhou B, Zhou Y, Zhu L, Zhu Z, Zhu H, Zhu X, Ziegler G, Zilka S, Zisserman A, Zito G, Zito G, Zu C, Zulfigar A.

Author information

  • 1Dementia Research Centre, UCL Institute of Neurology, London, UK. jschott@dementia.ion.ucl.ac.uk

Abstract

Defining cases and controls on the basis of biomarkers rather than clinical diagnosis may reduce sample sizes required for genetic studies. The aim of this study was to assess whether characterizing case/control status on the basis of cerebrospinal fluid (CSF) profile would increase power to replicate known genetic associations for Alzheimer's disease (AD). Independent of clinical diagnosis, Alzheimer's Disease Neuroimaging Initiative (ADNI) subjects with 2 CSF biomarkers for AD (Aβ1-42 < 192 pg/mL and tau phosphorylated at threonine 181 (p-tau) > 23 pg/mL, "CSF-positive") were compared with those without CSF evidence for AD (Aβ1-42 > 192 pg/mL and 181-phosphorylated tau < 23 pg/mL, "CSF-negative"). Minor allele frequency (MAF) and odds ratios (ORs) between these 2 groups were calculated for 7 single-nucleotide polymorphisms (SNPs) of interest. Two hundred thirty-two individuals were CSF-positive and 94 CSF-negative. There were no differences in age (74.7 ± 7.2 vs. 75.0 ± 6.5 years, p = 0.7), but significant differences in Mini Mental State Examination (MMSE) (25.9 ± 2.6 vs. 28.2 ± 1.7, p < 0.001) between the CSF-positive and CSF-negative groups. Significant differences in MAF (p < 0.05, uncorrected) were seen for CR1 (rs1408077; OR, 1.59; 95% confidence interval [CI], 1.01-2.49), PICALM (rs541458; OR, 0.68, 95% CI, 0.47-0.98), TOMM40 (rs2075650; OR, 4.30; 95% CI, 2.61-7.06); and possession of 1 or more APOE ε4 alleles (OR, 9.84; 95% CI, 5.48-17.67). These results suggest that using biomarkers of AD pathology to define case and control status may increase power in genetic association studies.

Copyright © 2012 Elsevier Inc. All rights reserved.

PMID:
21459483
[PubMed - indexed for MEDLINE]
PMCID:
PMC3150628
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