Fine mapping of genetic variants in BIN1, CLU, CR1 and PICALM for association with cerebrospinal fluid biomarkers for Alzheimer’s disease.
PLoS ONE. 2011-02-09; 6(2): e15918
DOI: 10.1371/journal.pone.0015918
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Kauwe JS, Cruchaga C, Karch CM, Sadler B, Lee M, Mayo K, Latu W, Su’a M, Fagan
AM, Holtzman DM, Morris JC; Alzheimer’s Disease Neuroimaging Initiative, Goate
AM.
Collaborators: Saradha A, Abdi H, Abeliovich A, Abellan van Kan G, Abner E,
Acharya D, Adams N, Adler D, Agrusti A, Agyemang A, Ahdidan J, Ahn JE, Aisen P,
Aksu Y, Al-Akhras M, Alarcon M, Alberca R, Alexander G, Alexander D, Almeida F,
Amlien I, Anand S, Andrew M, Angersbach S, Anjum A, Aoyama E, Arfanakis K, Armor
T, Arnold S, Asatryan A, Ashe-McNalley C, Ashiga H, Assareh A, Le Page A, Avants
B, Avinash G, Awasthi S, Ayan-Oshodi M, Babic T, Baek Y, Bagci U, Bai S, Baird G,
Baker J, Banks S, Bard J, Barnes J, Barret O, Bartlett J, Bartzokis G, Barua N,
Bauer C, Becker J, Becker JA, Beckett L, Bednar M, Beg MF, Bek S, Belmokhtar N,
Bernard C, Bertram L, Bhaskar U, Biffi A, Bigler E, Bilgic B, Bishop C, Bishop C,
Bittner D, Black R, Blennow K, Bogorodzki P, Bokde A, Bonner-Jackson A, Boppana
M, Bourgeat P, Bowes M, Bowman G, Braskie M, Braunewell K, Breitner J, Brewer J,
Brickman A, Britschgi M, Broadbent S, Brogren J, Brooks D, Browndyke J, Brunton
S, Buchert R, Buchsbaum M, Buckley C, Buerger K, Burger C, Burnham S, Burns J,
Burton D, Butman J, Cabeza R, Cairns N, Callhoff J, Callhoff J, Calvini P,
Cantillon M, Capella H, Cardona-Sanclemente LE, Carle A, Carmasin J, Carranza-Ath
F, Casabianca J, Casanova R, Cash D, Cedarbaum J, Cella M, Celsis P, Chaney M,
Chanu P, Chao L, Charil A, Chemali Z, Chen K, Chen M, Chen R, Chen B, Chen J,
Chen G, Chen W, Cheng WC, Chertkow H, Cheung C, Cheung V, Chiang G, Chiba K, Chin
S, Chisholm J, Cho Y, Choe J, Choubey S, Christensen AL, Clark C, Clark D,
Clarkson M, Clayton D, Clunie D, Coimbra A, Compton D, Coppola G, Cover KS, Crane
P, Crans G, Croop R, Crowther D, Crum W, Cui Y, Curry C, Curtis S, Cutter G,
Daiello L, Dake M, Dale A, Daliri MR, Damato VD, Darby E, Darkner S, Darkner S,
Davatzikos C, Dave J, David R, Davidson J, de Bruijne M, De Meyer G, De Nunzio G,
DeCarli C, Dechairo B, DeDuck K, Dehghan H, Dejkam A, Delfino M, Dellavedova L,
Delpassand E, Delrieu J, Deniz O, Denney D, DeOrchis V, Dépy Carron D,
deToledo-Morrell L, Devanand D, Devanarayan V, Diaz-Arrastia R, Dickerson B, Ding
X, Dinov I, Dobson H, Dodge H, Donohue M, Dore V, Dorflinger E, Dowling M, Duan
X, Dubal D, Duchesne S, Duff K, Dukart J, Durazzo T, Dykstra K, Earl N, Edula G,
Ekin A, Elcoroaristizabal X, Emahazion T, Engelman C, Epstein N, Erten-Lyons D,
Eskildsen S, Falcone G, Fan Y, Fan L, Farb N, Farnum M, Farrer L, Farzan A, Faux
N, Feldman H, Feldman S, Fennema-Notestine C, Fernandes M, Fernandez E, Ferrarini
L, Ferreira MJ, Ferrer E, Figurski M, Filipovych R, Fillit H, Finch S, Finlay D,
Fiot JB, Flenniken D, Fletcher PT, Fletcher E, Flynn Longmire C, Focke N, Forman
M, Forsythe A, Fox S, Fox-Bosetti S, Francis AL, Franco-Villalobos C, Franko E,
Freeman S, Friedrich CM, Friesenhahn M, Frings L, Frisoni G, Fritzsche K,
Fujimoto Y, Fujiwara K, Fullerton T, Furney S, Gallins P, Gamst A, Gan K, Garcia
MT, Garg G, Gaser C, Gastineau E, Gauthier S, Gavett B, Gavidia G, Gazdzinski S,
Ge Q, Gemme G, Geraci J, German D, Ghassabi Z, Gieschke R, Gil JE, Gill R,
Gitelman D, Gleason C, Godbey M, Goghari V, Gold M, Goldberg T, Gomeni R, Gong S,
Gonzales C, Goodro R, Gordon B, Gorriz JM, Grachev I, Grandey E, Grasela T, Gratt
J, Gray K, Greenberg B, Gregg K, Gregory E, Greicius M, Greve D, Grill J, Gross
A, Gross A, Guignot I, Guo Q, Guo H, Guo L, Guo J, Habeck C, Hai Y, Haight T,
Hammarstrom P, Hampel H, Han J, Han T, Hanif M, Hanna Y, Hardy P, Harvey D, Hasan
MK, Hayashi T, Hazart A, He H, He Y, Head D, Head D, Heckemann R, Heidebrink J,
Henderson D, Henrard S, Herholz K, Hernandez M, Herskovits AZ, Hess C,
Hildenbrand M, Hobart J, Hoffman J, Holder D, Honigberg L, Hoppin J, Horsfield M,
Hou Y, Hsu A, Hsu WW, Hu Z, Hu X, Hu Z, Hu W, Hu Z, Huang CC, Huang C, Huang S,
Huang Y, Huang J, Huang CJ, Huang SP, Huang F, Hubbard R, Huentelman M, Hui S,
Huppertz HJ, Hurko O, Hurt S, Huyck S, Hwang S, Hyun J, Ifeachor E, Iglesias M,
Ikari Y, Ikonomidou V, Immermann F, Inoue L, Insel P, Irizarry M, Irungu Bm,
Ishibashi T, Ishii K, Ismail S, Ismail S, Ito K, Iturria-Medina Y, Iwatsubo T,
Iyer M, Jacobson M, Jafari A, Jafari-Khouzani K, Jaffe C, Jagust W, Jagust W,
Jara H, Jasperse B, Jedynak B, Jefferson A, Jennings JR, Jessen W, Jia F, Jiang
T, Jing H, Johnson DK, Jones R, Juengling F, Juh R, Julin P, Uday Bhaskar K,
Kadish B, Kahle-Wrobleski K, Kallam HR, Kamboh MI, Kaneko T, Kaneta T,
Karageorgiou E, Karantzoulis S, Karlawish J, Katz E, Kaushik SS, Kauwe J,
Kawakami H, Kazimipoor B, Kelleher T, Kennedy R, Kerr D, Kerrouche N, Khalil I,
Khalil A, Killeen N, Killiany R, Kim A, Kim Y, Kim H, Kim JH, Kim H, Kim S, Kim
H, Kim H, Kimberg D, Kimura T, King R, Kirby J, Kirsch W, Klimas M, Kline R,
Kling M, Klopfenstein E, Kobayashi D, Koikkalainen J, Kokomoor A, Kolasny A,
Koppel J, Korolev I, Kotran N, Kouassi A, Kowalczyk A, Kozma L, Kratzer M,
Kuceyeski A, Kuhn FP, Kulkarni M, Kumar S, Kuo HT, Kuo J, Kurosawa K, Kwon Oh,
Laforet G, Lai S, Lakatos A, Lam OK, Lampron A, Landau S, Landen J, Lane R,
Langbaum J, Langford D, Lanius V, Lavault R, Laxamana J, Le T, Leahy R, Lee N,
Lee D, Lee V, Lee JH, Lee JM, Lefkimmiatis S, Lemaitre H, Lenz R, Lester G, Levey
A, Li W, Li S, Li X, Li G, Li M, Li CS, Li L, Li J, Li Q, Li Y, Li R, Li SJ,
Liang P, Liang L, Liang K, Liao YL, Lin LC, Lin M, Lin AL, Lin L, Liu T, Liu M,
Liu T, Liu L, Liu X, Liu S, Liu D, Liu S, Liu Y, Liu P, Lo R, Lobanov V,
Loewenstein D, Logovinsky V, Long X, Long Z, Looi J, Lu PH, Lukic A, Lull JJ, Luo
X, Lynch J, Ma L, Mackin S, Magda S, Maglio S, Mak HK, Malave V, Maldjian J,
Mandal P, Mangin JF, Manjon J, Manohar D, Mansouri C, Mantri N, Manzour A,
Marambaud P, Marchewka A, Marek K, Markind S, Marshall G, Martinez Torteya A,
Mather M, Mathis C, Matoug S, Matsuo Y, Matthews D, McArdle J, McEvoy L, McGeown
W, McIntyre J, McQuail J, Meadowcroft M, Meda S, Mehta N, Mendonca B, Menendez M,
Meredith J, Merrill D, Mesulam MM, Metti A, Meyer C, Mez J, Mickael G, Miftahof
R, Mikhno A, Miller D, Millikin C, Min Y, Mirza M, Mitsis E, Mohan A, Montana G,
Moore D, Moradi Birgani P, Moratal D, Morimoto B, Mortamet B, Moscato P, Motyl R,
Mueller K, Mueller S, Mueller N, Mukherjee S, Mulder E, Murayama S, Murphy M,
Murray B, Musiek E, Myers A, Najafi S, Nazarparvar B, Nazeri A, Nettiksimmons J,
Neu S, Neves S, Ng YB, Nguyen N, Nguyen Xuan T, Nicodemus K, Niecko T, Nielsen C,
Notomi K, Nuneez Benjumea F, O’Bryant S, O’Neil A, Obisesan T, Oh DH, Oh J,
Okonkwo O, Olde Rikkert M, Olmos S, Ortner M, Ostrowitzki S, Oswald A, Ott B,
Ourselin S, Ouyang G, Paiva R, Pan Z, Pande Y, Pardo J, Pardoe H, Park H, Park
MH, Park Sh, Park KH, Park S, Parsey R, Parveen R, Paskavitz J, Patel Y, Patil M,
Pawlak M, Payoux P, Pearson J, Peavy G, Pell G, Peng Y, Pennec X, Pepin Jl, Perea
R, Perneczky R, Petitti D, Petrella J, Peyrat JM, Pezoa J, Pham CT, Phillips N,
Pierson R, Piovezan M, Podhorski A, Pollari M, Pontecorvo M, Poppenk J, Posner H,
Potkin S, Potter E, Poulin S, Prasad G, Prenger K, Prince J, Priya A, Puchakayala
SR, Puchakayala SR, Qiu A, Qiu R, Qiu W, Qualls CD, Rabie H, Rajeesh R,
Rallabandi VP, Ramage A, Randolph C, Rao A, Rao D, Raubertas R, Ray D, Razak H,
Redolfi A, Reed B, Reid A, Reilhac A, Reinsberger C, Restrepo L, Retico A,
Rezaeitabar Y, Richards J, Richter M, Riddle W, Ries M, Rincón M, Rischall M,
Robieson W, Rocha-Rego V, Rogalski E, Rogers E, Rojas I, Rojas Balderrama J,
Romero K, Rorden C, Rosand J, Rosen A, Rosen O, Rosenberg P, Ross D, Ross J,
Roubini E, Rousseau F, Rowe C, Rubin D, Rubright J, Ruiz A, Rusinek H, Ryan L,
Saad A, Sabbagh M, Sabuncu M, Sachs M, Sacuiu S, Sadeghi A, Said Y, Saint-Aubert
L, Sakata M, Salat D, Salmon D, Salomi S, Salter H, Samwald M, Sanchez L, Sanders
E, Sanjo N, Sarnel H, Sato S, Sato H, Saumier D, Savio A, Sawada I, Saykin A,
Schaffer JD, Scharre D, Schegerin M, Schlosser G, Schmand B, Schmansky N, Schmidt
M, Schneider L, Schramm H, Schuerch M, Schwartz C, Schwartz E, Schwarz A,
Seethamraju R, Seixas F, Selnes P, Senjem M, Senlin W, Seo SW, Sethuraman G,
Sevigny J, Sevigny J, Sfikas G, Sghedoni R, Shah SK, Shahbaba B, Shams S,
Shattuck D, Shaw L, Shaw L, Sheela J, Shen W, Shen Q, Shera D, Sherman J, Sherva
R, Shi F, Shukla V, Shuler C, Shulman J, Siegel R, Siemers E, Silveira M, Silver
M, Silverman D, Sim I, Simmons A, Simmons A, Simoes R, Simon M, Simpson I, Singh
SP, Singh N, Siuciak J, Sjögren N, Skup M, Small G, Smith M, Smith C, Smith B,
Smyth T, Snow S, Soares H, Soldea O, Solomon A, Solomon P, Som S, Song C, Song M,
Sorensen G, Soudah E, Spampinato MV, Spenger C, Sperling R, Spiegel R, Spies L,
Squarcia S, Squire L, Staff R, Stern Y, Straw J, Strittmatter S, Stühler E,
Styren S, Subramanian V, Sugishita M, Sukkar R, Sun Y, Sun Y, Sun J, Sun J,
Sundell K, Suri M, Suzuki A, Svetnik V, Swan M, Takahasi T, Takeuchi T, Tanaka S,
Tancredi D, Tang S, Tao D, Tao W, Tariot P, Taylor-Reinwald L, Teng E, Terlizzi
R, Thiele F, Thomas R, Thomas B, Thompson P, Thompson W, Thornton-Wells T,
Thurfjell L, Titeux L, Tokuda T, Toledo JB, Tolli T, Toma A, Tomita N, Toro R,
Tosun D, Tousian M, Toussaint P, Toyoshiba H, Tractenberg RE, Trittschuh E,
Trojanowski J, Truran D, Tsechpenakis G, Tucker-Drob E, Tufail A, Tung J, Ueda Y,
Ullrich L, Umadevi Venkataraju K, Umar N, Uzunbas G, Van de Nes J, van der Brug
M, Van Horn J, Van Leemput K, Van Train K, Van Zeeland A, Vasanawala M, Vemuri P,
Verwaerde P, Videbaek C, Vidoni E, Vigneron V, Villanueva-Meyer J, Visser PJ,
Vitolo O, Vounou M, Wade S, Walhovd KB, Wan H, Wang L, Wang X, Wang Z, Wang A,
Wang T, Wang YM, Wang Y, Wang W, Wang H, Wang Y, Wang LS, Wang H, Wang A, Wang Y,
Wang L, Ward M, Warfield S, Waring S, Watanabe T, Webb D, Wei L, Weiner M, Wen
SH, Wenjing L, Wenzel F, Westlye LT, Whitcher B, Whitlow C, Whitwell J,
Wilhelmsen K, Williams D, Wilmot B, Wingo T, Winkler A, Wiste H, Wolfson T, Wolke
I, Wolz R, Woo J, Woo E, Woods L, Worth A, Worth E, Wouters H, Wu T, Wu E, Wu YG,
Wu L, Wu X, Wyman B, Wyss-Coray T, Xiao L, Xiao G, Xie S, Xu J, Xu Y, Xu YZ, Xu
G, Yamane T, Yamashita F, Yan Y, Yan Y, Yan P, Yang J, Yang QX, Yang Z, Yang G,
Yang W, Yang E, Yang Z, Ye J, Ye J, Ye L, Ye BS, Yee L, Yesavage J, Ying S, Yoo
B, Young J, Yu D, Yu S, Yuan K, Yuan G, Yushkevich P, Zaborszky L, Zagorodnov V,
Zagorski M, Zawadzki R, Zeitzer J, Zhang H, Zhang T, Zhang H, Zhang P, Zhang X,
Zhang B, Zhang J, Zhang L, Zhang L, Zhang K, Zhao J, Zhao P, Zhao Q, Zhen X, Zhen
X, Zheng Y, Zhijun Y, Zhou S, Zhou B, Zhu W, Zhu H, Zhu W, Zito G, Zou H.
Recent genome-wide association studies of Alzheimer’s disease (AD) have
identified variants in BIN1, CLU, CR1 and PICALM that show replicable association
with risk for disease. We have thoroughly sampled common variation in these
genes, genotyping 355 variants in over 600 individuals for whom measurements of
two AD biomarkers, cerebrospinal fluid (CSF) 42 amino acid amyloid beta fragments
(Aβ(42)) and tau phosphorylated at threonine 181 (ptau(181)), have been obtained.
Association analyses were performed to determine whether variants in BIN1, CLU,
CR1 or PICALM are associated with changes in the CSF levels of these biomarkers.
Despite adequate power to detect effects as small as a 1.05 fold difference, we
have failed to detect evidence for association between SNPs in these genes and
CSF Aβ(42) or ptau(181) levels in our sample. Our results suggest that these
variants do not affect risk via a mechanism that results in a strong additive
effect on CSF levels of Aβ(42) or ptau(181).