Novel genetic loci associated with hippocampal volume.
Novel genetic loci associated with hippocampal volume.
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与海马体积相关的新型遗传基因座。
DOI：
10.1038/ncomms13624
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发表时间：
2017-01-18
影响因子：
16.6
通讯作者：
Ikram MA
中科院分区：
文献类型：
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作者：
Hibar DP;Adams HHH;Jahanshad N;Chauhan G;Stein JL;Hofer E;Renteria ME;Bis JC;Arias-Vasquez A;Ikram MK;Desrivières S;Vernooij MW;Abramovic L;Alhusaini S;Amin N;Andersson M;Arfanakis K;Aribisala BS;Armstrong NJ;Athanasiu L;Axelsson T;Beecham AH;Beiser A;Bernard M;Blanton SH;Bohlken MM;Boks MP;Bralten J;Brickman AM;Carmichael O;Chakravarty MM;Chen Q;Ching CRK;Chouraki V;Cuellar-Partida G;Crivello F;Den Braber A;Doan NT;Ehrlich S;Giddaluru S;Goldman AL;Gottesman RF;Grimm O;Griswold ME;Guadalupe T;Gutman BA;Hass J;Haukvik UK;Hoehn D;Holmes AJ;Hoogman M;Janowitz D;Jia T;Jørgensen KN;Karbalai N;Kasperaviciute D;Kim S;Klein M;Kraemer B;Lee PH;Liewald DCM;Lopez LM;Luciano M;Macare C;Marquand AF;Matarin M;Mather KA;Mattheisen M;McKay DR;Milaneschi Y;Muñoz Maniega S;Nho K;Nugent AC;Nyquist P;Loohuis LMO;Oosterlaan J;Papmeyer M;Pirpamer L;Pütz B;Ramasamy A;Richards JS;Risacher SL;Roiz-Santiañez R;Rommelse N;Ropele S;Rose EJ;Royle NA;Rundek T;Sämann PG;Saremi A;Satizabal CL;Schmaal L;Schork AJ;Shen L;Shin J;Shumskaya E;Smith AV;Sprooten E;Strike LT;Teumer A;Tordesillas-Gutierrez D;Toro R;Trabzuni D;Trompet S;Vaidya D;Van der Grond J;Van der Lee SJ;Van der Meer D;Van Donkelaar MMJ;Van Eijk KR;Van Erp TGM;Van Rooij D;Walton E;Westlye LT;Whelan CD;Windham BG;Winkler AM;Wittfeld K;Woldehawariat G;Wolf C;Wolfers T;Yanek LR;Yang J;Zijdenbos A;Zwiers MP;Agartz I;Almasy L;Ames D;Amouyel P;Andreassen OA;Arepalli S;Assareh AA;Barral S;Bastin ME;Becker DM;Becker JT;Bennett DA;Blangero J;van Bokhoven H;Boomsma DI;Brodaty H;Brouwer RM;Brunner HG;Buckner RL;Buitelaar JK;Bulayeva KB;Cahn W;Calhoun VD;Cannon DM;Cavalleri GL;Cheng CY;Cichon S;Cookson MR;Corvin A;Crespo-Facorro B;Curran JE;Czisch M;Dale AM;Davies GE;De Craen AJM;De Geus EJC;De Jager PL;De Zubicaray GI;Deary IJ;Debette S;DeCarli C;Delanty N;Depondt C;DeStefano A;Dillman A;Djurovic S;Donohoe G;Drevets WC;Duggirala R;Dyer TD;Enzinger C;Erk S;Espeseth T;Fedko IO;Fernández G;Ferrucci L;Fisher SE;Fleischman DA;Ford I;Fornage M;Foroud TM;Fox PT;Francks C;Fukunaga M;Gibbs JR;Glahn DC;Gollub RL;Göring HHH;Green RC;Gruber O;Gudnason V;Guelfi S;Håberg AK;Hansell NK;Hardy J;Hartman CA;Hashimoto R;Hegenscheid K;Heinz A;Le Hellard S;Hernandez DG;Heslenfeld DJ;Ho BC;Hoekstra PJ;Hoffmann W;Hofman A;Holsboer F;Homuth G;Hosten N;Hottenga JJ;Huentelman M;Hulshoff Pol HE;Ikeda M;Jack CR Jr;Jenkinson M;Johnson R;Jönsson EG;Jukema JW;Kahn RS;Kanai R;Kloszewska I;Knopman DS;Kochunov P;Kwok JB;Lawrie SM;Lemaître H;Liu X;Longo DL;Lopez OL;Lovestone S;Martinez O;Martinot JL;Mattay VS;McDonald C;McIntosh AM;McMahon FJ;McMahon KL;Mecocci P;Melle I;Meyer-Lindenberg A;Mohnke S;Montgomery GW;Morris DW;Mosley TH;Mühleisen TW;Müller-Myhsok B;Nalls MA;Nauck M;Nichols TE;Niessen WJ;Nöthen MM;Nyberg L;Ohi K;Olvera RL;Ophoff RA;Pandolfo M;Paus T;Pausova Z;Penninx BWJH;Pike GB;Potkin SG;Psaty BM;Reppermund S;Rietschel M;Roffman JL;Romanczuk-Seiferth N;Rotter JI;Ryten M;Sacco RL;Sachdev PS;Saykin AJ;Schmidt R;Schmidt H;Schofield PR;Sigursson S;Simmons A;Singleton A;Sisodiya SM;Smith C;Smoller JW;Soininen H;Steen VM;Stott DJ;Sussmann JE;Thalamuthu A;Toga AW;Traynor BJ;Troncoso J;Tsolaki M;Tzourio C;Uitterlinden AG;Hernández MCV;Van der Brug M;van der Lugt A;van der Wee NJA;Van Haren NEM;van 't Ent D;Van Tol MJ;Vardarajan BN;Vellas B;Veltman DJ;Völzke H;Walter H;Wardlaw JM;Wassink TH;Weale ME;Weinberger DR;Weiner MW;Wen W;Westman E;White T;Wong TY;Wright CB;Zielke RH;Zonderman AB;Martin NG;Van Duijn CM;Wright MJ;Longstreth WT;Schumann G;Grabe HJ;Franke B;Launer LJ;Medland SE;Seshadri S;Thompson PM;Ikram MA
海马结构是一种与情景记忆、空间导航、认知和应激反应密切相关的大脑结构。在几种常见的神经精神疾病中发现了海马体积和形状的结构异常。为了确定海马结构的遗传基础，我们在此对33536人进行了一项全基因组关联研究（GWAS），并发现了6个与海马体积显著相关的独立基因座，其中4个是新的。在这些新的基因座中，3个位于基因（ASTN2、DPP4和MAST4）内，1个位于SHH上游200kb处。一项海马亚区分析表明，MSRB3基因内的一个基因座显示出沿齿状回、下托、CA1和海马裂有局部效应的证据。此外，我们表明与海马体积减小相关的遗传变异也与阿尔茨海默病风险增加相关（rg = -0.155）。我们的研究结果提示了人类遗传变异影响海马体积和神经精神疾病风险的新的生物学途径。
哺乳动物大脑中的海马体在个体之间大小不同。在这里，希巴尔及其同事进行了一项全基因组关联荟萃分析，以找到6个与海马体体积有显著关联的基因座。
The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg=−0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness. The hippocampus in mammalian brain varies in size across individuals. Here, Hibar and colleagues perform a genome-wide association meta-analysis to find six genetic loci with significant association to hippocampus volume.