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Validating GWAS-Identified Risk Loci for Alzheimer’s Disease in Han Chinese Populations

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Abstract

In recent years, genome-wide association studies (GWASs) have identified many novel susceptible genes/loci for Alzheimer’s disease (AD). However, most of these studies were conducted in European and populations of European origin, and limited studies have been performed in Han Chinese. In this study, we genotyped 14 single-nucleotide polymorphisms (SNPs) in eight GWAS-reported AD risk genes in 1509 individuals comprising two independent Han Chinese case-control cohorts. Four SNPs (rs11234495, rs592297, rs676733, and rs3851179) in the PICALM gene were significantly associated with late-onset (LO)-AD in populations from Southwest China, whereas SNPs rs744373 (BIN1), rs9331942 (CLU), and rs670139 (MS4A4E) were linked to LO-AD in populations from East China. In the combined Han Chinese population, positive associations were observed between PICALM, CLU, MS4A4E genes, and LO-AD. The association between rs3851179 (PICALM), rs744373 (BIN1), and AD was further confirmed by meta-analysis of Asian populations. Our study verified the association between PICALM, BIN1, CLU, and MS4A4E variants and AD susceptibility in Han Chinese populations. We also discerned some regional differences concerning AD susceptibility SNPs.

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References

  1. Dickson TC, Vickers JC (2001) The morphological phenotype of beta-amyloid plaques and associated neuritic changes in Alzheimer’s disease. Neuroscience 105(1):99–107

    Article  CAS  PubMed  Google Scholar 

  2. Tanzi RE (2012) The genetics of Alzheimer disease. Cold Spring Harb Perspect Med 2(10) pii: a006296. doi:10.1101/cshperspect.a006296.

  3. Ertekin-Taner N (2007) Genetics of Alzheimer’s disease: a centennial review. Neurol Clin 25(3):611–667, v

    Article  PubMed  PubMed Central  Google Scholar 

  4. Zetzsche T, Rujescu D, Hardy J, Hampel H (2010) Advances and perspectives from genetic research: development of biological markers in Alzheimer’s disease. Expert Rev Mol Diagn 10(5):667–690

    Article  CAS  PubMed  Google Scholar 

  5. Tanzi RE, Bertram L (2005) Twenty years of the Alzheimer’s disease amyloid hypothesis: a genetic perspective. Cell 120(4):545–555

    Article  CAS  PubMed  Google Scholar 

  6. Scheuner D, Eckman C, Jensen M, Song X, Citron M, Suzuki N, Bird TD, Hardy J, Hutton M, Kukull W, Larson E, Levy-Lahad E, Viitanen M, Peskind E, Poorkaj P, Schellenberg G, Tanzi R, Wasco W, Lannfelt L, Selkoe D, Younkin S (1996) Secreted amyloid beta-protein similar to that in the senile plaques of Alzheimer’s disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer’s disease. Nat Med 2(8):864–870

    Article  CAS  PubMed  Google Scholar 

  7. Hollingworth P, Harold D, Sims R, Gerrish A, Lambert JC, Carrasquillo MM, Abraham R, Hamshere ML, Pahwa JS, Moskvina V, Dowzell K, Jones N, Stretton A, Thomas C, Richards A, Ivanov D, Widdowson C, Chapman J, Lovestone S, Powell J, Proitsi P, Lupton MK, Brayne C, Rubinsztein DC, Gill M, Lawlor B, Lynch A, Brown KS, Passmore PA, Craig D, McGuinness B, Todd S, Holmes C, Mann D, Smith AD, Beaumont H, Warden D, Wilcock G, Love S, Kehoe PG, Hooper NM, Vardy ER, Hardy J, Mead S, Fox NC, Rossor M, Collinge J, Maier W, Jessen F, Ruther E, Schurmann B, Heun R, Kolsch H, van den Bussche H, Heuser I, Kornhuber J, Wiltfang J, Dichgans M, Frolich L, Hampel H, Gallacher J, Hull M, Rujescu D, Giegling I, Goate AM, Kauwe JS, Cruchaga C, Nowotny P, Morris JC, Mayo K, Sleegers K, Bettens K, Engelborghs S, De Deyn PP, Van Broeckhoven C, Livingston G, Bass NJ, Gurling H, McQuillin A, Gwilliam R, Deloukas P, Al-Chalabi A, Shaw CE, Tsolaki M, Singleton AB, Guerreiro R, Muhleisen TW, Nothen MM, Moebus S, Jockel KH, Klopp N, Wichmann HE, Pankratz VS, Sando SB, Aasly JO, Barcikowska M, Wszolek ZK, Dickson DW, Graff-Radford NR, Petersen RC, van Duijn CM, Breteler MM, Ikram MA, DeStefano AL, Fitzpatrick AL, Lopez O, Launer LJ, Seshadri S, Berr C, Campion D, Epelbaum J, Dartigues JF, Tzourio C, Alperovitch A, Lathrop M, Feulner TM, Friedrich P, Riehle C, Krawczak M, Schreiber S, Mayhaus M, Nicolhaus S, Wagenpfeil S, Steinberg S, Stefansson H, Stefansson K, Snaedal J, Bjornsson S, Jonsson PV, Chouraki V, Genier-Boley B, Hiltunen M, Soininen H, Combarros O, Zelenika D, Delepine M, Bullido MJ, Pasquier F, Mateo I, Frank-Garcia A, Porcellini E, Hanon O, Coto E, Alvarez V, Bosco P, Siciliano G, Mancuso M, Panza F, Solfrizzi V, Nacmias B, Sorbi S, Bossu P, Piccardi P, Arosio B, Annoni G, Seripa D, Pilotto A, Scarpini E, Galimberti D, Brice A, Hannequin D, Licastro F, Jones L, Holmans PA, Jonsson T, Riemenschneider M, Morgan K, Younkin SG, Owen MJ, O’Donovan M, Amouyel P, Williams J (2011) Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer’s disease. Nat Genet 43(5):429–435

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Naj AC, Jun G, Beecham GW, Wang LS, Vardarajan BN, Buros J, Gallins PJ, Buxbaum JD, Jarvik GP, Crane PK, Larson EB, Bird TD, Boeve BF, Graff-Radford NR, De Jager PL, Evans D, Schneider JA, Carrasquillo MM, Ertekin-Taner N, Younkin SG, Cruchaga C, Kauwe JS, Nowotny P, Kramer P, Hardy J, Huentelman MJ, Myers AJ, Barmada MM, Demirci FY, Baldwin CT, Green RC, Rogaeva E, St George-Hyslop P, Arnold SE, Barber R, Beach T, Bigio EH, Bowen JD, Boxer A, Burke JR, Cairns NJ, Carlson CS, Carney RM, Carroll SL, Chui HC, Clark DG, Corneveaux J, Cotman CW, Cummings JL, DeCarli C, DeKosky ST, Diaz-Arrastia R, Dick M, Dickson DW, Ellis WG, Faber KM, Fallon KB, Farlow MR, Ferris S, Frosch MP, Galasko DR, Ganguli M, Gearing M, Geschwind DH, Ghetti B, Gilbert JR, Gilman S, Giordani B, Glass JD, Growdon JH, Hamilton RL, Harrell LE, Head E, Honig LS, Hulette CM, Hyman BT, Jicha GA, Jin LW, Johnson N, Karlawish J, Karydas A, Kaye JA, Kim R, Koo EH, Kowall NW, Lah JJ, Levey AI, Lieberman AP, Lopez OL, Mack WJ, Marson DC, Martiniuk F, Mash DC, Masliah E, McCormick WC, McCurry SM, McDavid AN, McKee AC, Mesulam M, Miller BL, Miller CA, Miller JW, Parisi JE, Perl DP, Peskind E, Petersen RC, Poon WW, Quinn JF, Rajbhandary RA, Raskind M, Reisberg B, Ringman JM, Roberson ED, Rosenberg RN, Sano M, Schneider LS, Seeley W, Shelanski ML, Slifer MA, Smith CD, Sonnen JA, Spina S, Stern RA, Tanzi RE, Trojanowski JQ, Troncoso JC, Van Deerlin VM, Vinters HV, Vonsattel JP, Weintraub S, Welsh-Bohmer KA, Williamson J, Woltjer RL, Cantwell LB, Dombroski BA, Beekly D, Lunetta KL, Martin ER, Kamboh MI, Saykin AJ, Reiman EM, Bennett DA, Morris JC, Montine TJ, Goate AM, Blacker D, Tsuang DW, Hakonarson H, Kukull WA, Foroud TM, Haines JL, Mayeux R, Pericak-Vance MA, Farrer LA, Schellenberg GD (2011) Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer’s disease. Nat Genet 43(5):436–441

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Lambert JC, Heath S, Even G, Campion D, Sleegers K, Hiltunen M, Combarros O, Zelenika D, Bullido MJ, Tavernier B, Letenneur L, Bettens K, Berr C, Pasquier F, Fievet N, Barberger-Gateau P, Engelborghs S, De Deyn P, Mateo I, Franck A, Helisalmi S, Porcellini E, Hanon O, de Pancorbo MM, Lendon C, Dufouil C, Jaillard C, Leveillard T, Alvarez V, Bosco P, Mancuso M, Panza F, Nacmias B, Bossu P, Piccardi P, Annoni G, Seripa D, Galimberti D, Hannequin D, Licastro F, Soininen H, Ritchie K, Blanche H, Dartigues JF, Tzourio C, Gut I, Van Broeckhoven C, Alperovitch A, Lathrop M, Amouyel P (2009) Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer’s disease. Nat Genet 41(10):1094–1099

    Article  CAS  PubMed  Google Scholar 

  10. Seshadri S, Fitzpatrick AL, Ikram MA, DeStefano AL, Gudnason V, Boada M, Bis JC, Smith AV, Carassquillo MM, Lambert JC, Harold D, Schrijvers EM, Ramirez-Lorca R, Debette S, Longstreth WT Jr, Janssens AC, Pankratz VS, Dartigues JF, Hollingworth P, Aspelund T, Hernandez I, Beiser A, Kuller LH, Koudstaal PJ, Dickson DW, Tzourio C, Abraham R, Antunez C, Du Y, Rotter JI, Aulchenko YS, Harris TB, Petersen RC, Berr C, Owen MJ, Lopez-Arrieta J, Varadarajan BN, Becker JT, Rivadeneira F, Nalls MA, Graff-Radford NR, Campion D, Auerbach S, Rice K, Hofman A, Jonsson PV, Schmidt H, Lathrop M, Mosley TH, Au R, Psaty BM, Uitterlinden AG, Farrer LA, Lumley T, Ruiz A, Williams J, Amouyel P, Younkin SG, Wolf PA, Launer LJ, Lopez OL, van Duijn CM, Breteler MM (2010) Genome-wide analysis of genetic loci associated with Alzheimer disease. JAMA: J Am Med Assoc 303(18):1832–1840

    Article  CAS  Google Scholar 

  11. Harold D, Abraham R, Hollingworth P, Sims R, Gerrish A, Hamshere ML, Pahwa JS, Moskvina V, Dowzell K, Williams A, Jones N, Thomas C, Stretton A, Morgan AR, Lovestone S, Powell J, Proitsi P, Lupton MK, Brayne C, Rubinsztein DC, Gill M, Lawlor B, Lynch A, Morgan K, Brown KS, Passmore PA, Craig D, McGuinness B, Todd S, Holmes C, Mann D, Smith AD, Love S, Kehoe PG, Hardy J, Mead S, Fox N, Rossor M, Collinge J, Maier W, Jessen F, Schurmann B, van den Bussche H, Heuser I, Kornhuber J, Wiltfang J, Dichgans M, Frolich L, Hampel H, Hull M, Rujescu D, Goate AM, Kauwe JS, Cruchaga C, Nowotny P, Morris JC, Mayo K, Sleegers K, Bettens K, Engelborghs S, De Deyn PP, Van Broeckhoven C, Livingston G, Bass NJ, Gurling H, McQuillin A, Gwilliam R, Deloukas P, Al-Chalabi A, Shaw CE, Tsolaki M, Singleton AB, Guerreiro R, Muhleisen TW, Nothen MM, Moebus S, Jockel KH, Klopp N, Wichmann HE, Carrasquillo MM, Pankratz VS, Younkin SG, Holmans PA, O’Donovan M, Owen MJ, Williams J (2009) Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer’s disease. Nat Genet 41(10):1088–1093

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Jun G, Naj AC, Beecham GW, Wang LS, Buros J, Gallins PJ, Buxbaum JD, Ertekin-Taner N, Fallin MD, Friedland R, Inzelberg R, Kramer P, Rogaeva E, St George-Hyslop P, Alzheimer’s Disease Genetics Consortium, Cantwell LB, Dombroski BA, Saykin AJ, Reiman EM, Bennett DA, Morris JC, Lunetta KL, Martin ER, Montine TJ, Goate AM, Blacker D, Tsuang DW, Beekly D, Cupples LA, Hakonarson H, Kukull W, Foroud TM, Haines J, Mayeux R, Farrer LA, Pericak-Vance MA, Schellenberg GD (2010) Meta-analysis confirms CR1, CLU, and PICALM as Alzheimer disease risk loci and reveals interactions with APOE genotypes. Arch Neurol 67(12):1473–1484

    Article  PubMed  PubMed Central  Google Scholar 

  13. Hu X, Pickering E, Liu YC, Hall S, Fournier H, Katz E, Dechairo B, John S, Van Eerdewegh P, Soares H, Alzheimer’s Disease Neuroimaging Initiative (2011) Meta-analysis for genome-wide association study identifies multiple variants at the BIN1 locus associated with late-onset Alzheimer’s disease. PLoS One 6(2):e16616

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Kamboh MI, Demirci FY, Wang X, Minster RL, Carrasquillo MM, Pankratz VS, Younkin SG, Saykin AJ, Jun G, Baldwin C, Logue MW, Buros J, Farrer L, Pericak-Vance MA, Haines JL, Sweet RA, Ganguli M, Feingold E, Dekosky ST, Lopez OL, Barmada MM (2012) Genome-wide association study of Alzheimer’s disease. Transl Psychiatry 2:e117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Li HL, Shi SS, Guo QH, Ni W, Dong Y, Liu Y, Sun YM, Bei W, Lu SJ, Hong Z, Wu ZY (2011) PICALM and CR1 variants are not associated with sporadic Alzheimer’s disease in Chinese patients. J Alzheim Dis: JAD 25(1):111–117

    Google Scholar 

  16. Ferrari R, Moreno JH, Minhajuddin AT, O’Bryant SE, Reisch JS, Barber RC (1846) Momeni P (2012) Implication of common and disease specific variants in CLU, CR1, and PICALM. Neurobiol Aging 33(8):1846e7–1846e18

    Article  Google Scholar 

  17. Tan L, Yu JT, Zhang W, Wu ZC, Zhang Q, Liu QY, Wang W, Wang HF, Ma XY, Cui WZ (2013) Association of GWAS-linked loci with late-onset Alzheimer’s disease in a northern Han Chinese population. Alzheim Dement: J Alzheim Assoc 9(5):546–553

    Article  Google Scholar 

  18. Bi R, Zhao L, Zhang C, Lu W, Feng JQ, Wang Y, Ni J, Zhang J, Li GD, Hu QX, Wang D, Yao YG, Li T (2014) No association of the LRRK2 genetic variants with Alzheimer’s disease in Han Chinese individuals. Neurobiol Aging 35(2):444e5–444e9

    Article  Google Scholar 

  19. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM (1984) Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 34(7):939–944

    Article  CAS  PubMed  Google Scholar 

  20. Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, Roses AD, Haines JL, Pericak-Vance MA (1993) Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science 261(5123):921–923

    Article  CAS  PubMed  Google Scholar 

  21. Kurz A, Lautenschlager N, Haupt M, Zimmer R, von Thulen B, Altland K, Lauter H, Muller U (1994) The apolipoprotein E-epsilon 4 allele is a risk factor for Alzheimer disease with early and late onset. Nervenarzt 65(11):774–779

    CAS  PubMed  Google Scholar 

  22. Wang D, Feng JQ, Li YY, Zhang DF, Li XA, Li QW, Yao YG (2012) Genetic variants of the MRC1 gene and the IFNG gene are associated with leprosy in Han Chinese from Southwest China. Hum Genet 131(7):1251–1260

    Article  CAS  PubMed  Google Scholar 

  23. Gauderman WJ (2002) Sample size requirements for matched case–control studies of gene-environment interaction. Stat Med 21(1):35–50

    Article  PubMed  Google Scholar 

  24. Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, Sham PC (2007) PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81(3):559–575

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Barrett JC, Fry B, Maller J, Daly MJ (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21(2):263–265

    Article  CAS  PubMed  Google Scholar 

  26. Stephens M, Smith NJ, Donnelly P (2001) A new statistical method for haplotype reconstruction from population data. Am J Hum Genet 68(4):978–989

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Skol AD, Scott LJ, Abecasis GR, Boehnke M (2006) Joint analysis is more efficient than replication-based analysis for two-stage genome-wide association studies. Nat Genet 38(2):209–213

    Article  CAS  PubMed  Google Scholar 

  28. Consortium GT (2013) The Genotype-Tissue Expression (GTEx) project. Nat Genet 45(6):580–585

    Article  Google Scholar 

  29. Chen LH, Kao PY, Fan YH, Ho DT, Chan CS, Yik PY, Ha JC, Chu LW, Song YQ (2012) Polymorphisms of CR1, CLU and PICALM confer susceptibility of Alzheimer’s disease in a southern Chinese population. Neurobiol Aging 33(1):210e1–210e7

    Article  Google Scholar 

  30. Yu JT, Song JH, Ma T, Zhang W, Yu NN, Xuan SY, Tan L (2011) Genetic association of PICALM polymorphisms with Alzheimer’s disease in Han Chinese. J Neurol Sci 300(1–2):78–80

    Article  CAS  PubMed  Google Scholar 

  31. Ohara T, Ninomiya T, Hirakawa Y, Ashikawa K, Monji A, Kiyohara Y, Kanba S, Kubo M (2012) Association study of susceptibility genes for late-onset Alzheimer’s disease in the Japanese population. Psychiatr Genet 22(6):290–293

    Article  CAS  PubMed  Google Scholar 

  32. Tebar F, Bohlander SK, Sorkin A (1999) Clathrin assembly lymphoid myeloid leukemia (CALM) protein: localization in endocytic-coated pits, interactions with clathrin, and the impact of overexpression on clathrin-mediated traffic. Mol Biol Cell 10(8):2687–2702

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Koo EH, Squazzo SL (1994) Evidence that production and release of amyloid beta-protein involves the endocytic pathway. J Biol Chem 269(26):17386–17389

    CAS  PubMed  Google Scholar 

  34. Teixeira CM, Pomedli SR, Maei HR, Kee N, Frankland PW (2006) Involvement of the anterior cingulate cortex in the expression of remote spatial memory. J Neurosci: Off J Soc Neurosci 26(29):7555–7564

    Article  Google Scholar 

  35. Jiang T, Yu JT, Tan MS, Wang HF, Wang YL, Zhu XC, Zhang W, Tan L (2014) Genetic variation in PICALM and Alzheimer’s disease risk in Han Chinese. Neurobiol Aging 35(4):934e1–934e3

    Article  Google Scholar 

  36. Liu G, Zhang S, Cai Z, Ma G, Zhang L, Jiang Y, Feng R, Liao M, Chen Z, Zhao B, Li K (2013) PICALM gene rs3851179 polymorphism contributes to Alzheimer’s disease in an Asian population. Neruomol Med 15(2):384–388

    Article  CAS  Google Scholar 

  37. Liu G, Zhang S, Cai Z, Li Y, Cui L, Ma G, Jiang Y, Zhang L, Feng R, Liao M, Chen Z, Zhao B, Li K (2013) BIN1 gene rs744373 polymorphism contributes to Alzheimer’s disease in East Asian population. Neurosci Lett 544:47–51

    Article  CAS  PubMed  Google Scholar 

  38. Chapuis J, Hansmannel F, Gistelinck M, Mounier A, Van Cauwenberghe C, Kolen KV, Geller F, Sottejeau Y, Harold D, Dourlen P, Grenier-Boley B, Kamatani Y, Delepine B, Demiautte F, Zelenika D, Zommer N, Hamdane M, Bellenguez C, Dartigues JF, Hauw JJ, Letronne F, Ayral AM, Sleegers K, Schellens A, Broeck LV, Engelborghs S, De Deyn PP, Vandenberghe R, O’Donovan M, Owen M, Epelbaum J, Mercken M, Karran E, Bantscheff M, Drewes G, Joberty G, Campion D, Octave JN, Berr C, Lathrop M, Callaerts P, Mann D, Williams J, Buee L, Dewachter I, Van Broeckhoven C, Amouyel P, Moechars D, Dermaut B, Lambert JC, GERAD Consortium (2013) Increased expression of BIN1 mediates Alzheimer genetic risk by modulating tau pathology. Mol Psychiatry 18(11):1225–1234

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Karch CM, Jeng AT, Nowotny P, Cady J, Cruchaga C, Goate AM (2012) Expression of novel Alzheimer’s disease risk genes in control and Alzheimer’s disease brains. PLoS One 7(11):e50976

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Carrasquillo MM, Belbin O, Hunter TA, Ma L, Bisceglio GD, Zou F, Crook JE, Pankratz VS, Sando SB, Aasly JO, Barcikowska M, Wszolek ZK, Dickson DW, Graff-Radford NR, Petersen RC, Passmore P, Morgan K, Alzheimer’s Research UKc, Younkin SG (2011) Replication of EPHA1 and CD33 associations with late-onset Alzheimer’s disease: a multi-centre case–control study. Mol Neurodegener 6(1):54

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA, Hunter DJ, McCarthy MI, Ramos EM, Cardon LR, Chakravarti A, Cho JH, Guttmacher AE, Kong A, Kruglyak L, Mardis E, Rotimi CN, Slatkin M, Valle D, Whittemore AS, Boehnke M, Clark AG, Eichler EE, Gibson G, Haines JL, Mackay TF, McCarroll SA, Visscher PM (2009) Finding the missing heritability of complex diseases. Nature 461(7265):747–753

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Ma L, Tang J, Wang D, Zhang W, Liu W, Wang D, Liu XH, Gong W, Yao YG, Chen X (2013) Evaluating risk loci for schizophrenia distilled from genome-wide association studies in Han Chinese from Central China. Mol Psychiatry 18(6):638–639

    Article  CAS  PubMed  Google Scholar 

  43. Lambert JC, Ibrahim-Verbaas CA, Harold D, Naj AC, Sims R, Bellenguez C, Jun G, Destefano AL, Bis JC, Beecham GW, Grenier-Boley B, Russo G, Thornton-Wells TA, Jones N, Smith AV, Chouraki V, Thomas C, Ikram MA, Zelenika D, Vardarajan BN, Kamatani Y, Lin CF, Gerrish A, Schmidt H, Kunkle B, Dunstan ML, Ruiz A, Bihoreau MT, Choi SH, Reitz C, Pasquier F, Hollingworth P, Ramirez A, Hanon O, Fitzpatrick AL, Buxbaum JD, Campion D, Crane PK, Baldwin C, Becker T, Gudnason V, Cruchaga C, Craig D, Amin N, Berr C, Lopez OL, De Jager PL, Deramecourt V, Johnston JA, Evans D, Lovestone S, Letenneur L, Moron FJ, Rubinsztein DC, Eiriksdottir G, Sleegers K, Goate AM, Fievet N, Huentelman MJ, Gill M, Brown K, Kamboh MI, Keller L, Barberger-Gateau P, McGuinness B, Larson EB, Green R, Myers AJ, Dufouil C, Todd S, Wallon D, Love S, Rogaeva E, Gallacher J, St George-Hyslop P, Clarimon J, Lleo A, Bayer A, Tsuang DW, Yu L, Tsolaki M, Bossu P, Spalletta G, Proitsi P, Collinge J, Sorbi S, Sanchez-Garcia F, Fox NC, Hardy J, Naranjo MC, Bosco P, Clarke R, Brayne C, Galimberti D, Mancuso M, Matthews F, European Alzheimer’s Disease Initiative, Genetic, Environmental Risk in Alzheimer’s Disease, Alzheimer’s Disease Genetic Consortium, Cohorts for Heart and Aging Research in Genomic Epidemiology, Moebus S, Mecocci P, Del Zompo M, Maier W, Hampel H, Pilotto A, Bullido M, Panza F, Caffarra P, Nacmias B, Gilbert JR, Mayhaus M, Lannfelt L, Hakonarson H, Pichler S, Carrasquillo MM, Ingelsson M, Beekly D, Alvarez V, Zou F, Valladares O, Younkin SG, Coto E, Hamilton-Nelson KL, Gu W, Razquin C, Pastor P, Mateo I, Owen MJ, Faber KM, Jonsson PV, Combarros O, O’Donovan MC, Cantwell LB, Soininen H, Blacker D, Mead S, Mosley TH Jr, Bennett DA, Harris TB, Fratiglioni L, Holmes C, de Bruijn RF, Passmore P, Montine TJ, Bettens K, Rotter JI, Brice A, Morgan K, Foroud TM, Kukull WA, Hannequin D, Powell JF, Nalls MA, Ritchie K, Lunetta KL, Kauwe JS, Boerwinkle E, Riemenschneider M, Boada M, Hiltunen M, Martin ER, Schmidt R, Rujescu D, Wang LS, Dartigues JF, Mayeux R, Tzourio C, Hofman A, Nothen MM, Graff C, Psaty BM, Jones L, Haines JL, Holmans PA, Lathrop M, Pericak-Vance MA, Launer LJ, Farrer LA, van Duijn CM, Van Broeckhoven C, Moskvina V, Seshadri S, Williams J, Schellenberg GD, Amouyel P (2013) Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer’s disease. Nat Genet 45(12):1452–1458

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

We thank DNA donors in this study. We are grateful to the two anonymous reviewers for their helpful comments. This study was supported by the Strategic Priority Research Program (B) of the Chinese Academy of Sciences (XDB02020000).

Conflict of Interest

The authors declare that they have no conflict of interest

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Authors and Affiliations

  1. Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, 650223, China

    Hui-Zhen Wang, Rui Bi, Qiu-Xiang Hu, Qun Xiang, Deng-Feng Zhang, Wen Zhang & Yong-Gang Yao

  2. School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, 230026, China

    Hui-Zhen Wang

  3. Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, 650204, China

    Rui Bi, Qiu-Xiang Hu, Qun Xiang, Deng-Feng Zhang, Wen Zhang & Yong-Gang Yao

  4. Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China

    Chen Zhang & Yiru Fang

  5. The Mental Health Center and Psychiatric Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, 610064, China

    Xiaohong Ma, Wanjun Guo, Wei Deng, Liansheng Zhao, Peiyan Ni, Mingli Li & Tao Li

  6. The State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, 610064, China

    Xiaohong Ma, Wanjun Guo, Wei Deng, Liansheng Zhao, Peiyan Ni, Mingli Li & Tao Li

  7. Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, 650223, China

    Yong-Gang Yao

  8. CAS Center for Excellence in Brain Science, Chinese Academy of Sciences, Shanghai, 200031, China

    Yong-Gang Yao

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  3. Qiu-Xiang Hu
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  4. Qun Xiang
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  5. Chen Zhang
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  7. Wen Zhang
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  10. Wei Deng
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Corresponding author

Correspondence to Yong-Gang Yao.

Additional information

Hui-Zhen Wang and Rui Bi contributed equally to this study.

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Wang, HZ., Bi, R., Hu, QX. et al. Validating GWAS-Identified Risk Loci for Alzheimer’s Disease in Han Chinese Populations. Mol Neurobiol 53, 379–390 (2016). https://doi.org/10.1007/s12035-014-9015-z

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  • DOI: https://doi.org/10.1007/s12035-014-9015-z

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