Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease
Escott Price V;Bellenguez C;Wang LS;Choi SH;Harold D;Jones L;Holmans P;Gerrish A;Vedernikov A;Richards A;DeStefano AL;Lambert JC;Ibrahim Verbaas CA;Naj AC;Sims R;Jun G;Bis JC;Beecham GW;Grenier Boley B;Russo G;Thornton Wells TA;Denning N;Smith AV;Chouraki V;Thomas C;Ikram MA;Zelenika D;Vardarajan BN;Kamatani Y;Lin CF;Schmidt H;Kunkle B;Dunstan ML;Vronskaya M;United Kingdom Brain Expression Consortium;Johnson AD;Ruiz A;Bihoreau MT;Reitz C;Pasquier F;Hollingworth P;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;Hernández I;Rubinsztein DC;Eiriksdottir G;Sleegers K;Goate AM;Fiévet N;Huentelman MJ;Gill M;Brown K;Kamboh MI;Keller L;Barberger Gateau P;McGuinness B;Larson EB;Myers AJ;Dufouil C;Todd S;Wallon D;Love S;Rogaeva E;Gallacher J;George Hyslop PS;Clarimon J;Lleo A;Bayer A;Tsuang DW;Yu L;Tsolaki M;Bossù P;Spalletta G;Proitsi P;Collinge J;Sorbi S;Garcia FS;Fox NC;Hardy J;Naranjo MC;Bosco P;Clarke R;Brayne C;Galimberti D;Scarpini E;Bonuccelli U;Mancuso M;Siciliano G;Moebus S;Mecocci P;DEL ZOMPO, MARIA;Maier W;Hampel H;Pilotto A;Frank García A;Panza F;Solfrizzi V;Caffarra P;Nacmias B;Perry W;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;Dartigues JF;Mayeux R;Tzourio C;Hofman A;Nöthen MM;Graff C;Psaty BM;Haines JL;Lathrop M;Pericak Vance MA;Launer LJ;Van Broeckhoven C;Farrer LA;van Duijn CM;Ramirez A;Seshadri S;Schellenberg GD;Amouyel P;Williams J.
2014-01-01
Abstract
Background: Alzheimer’s disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer’s Project Consortium, comprising over 7 genotypes from 25,580 Alzheimer’s cases and 48,466 controls. Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.461026) and 14 (IGHV1-67 p = 7.961028) which indexed novel susceptibility loci. Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer’s disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer’s disease.