Novel genetic loci underlying human intracranial volume identified through genome-wide association.
Novel genetic loci underlying human intracranial volume identified through genome-wide association.
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DOI：
10.1038/nn.4398
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发表时间：
2016-12
影响因子：
25
通讯作者：
Thompson PM
中科院分区：
文献类型：
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作者：
Adams HH;Hibar DP;Chouraki V;Stein JL;Nyquist PA;Rentería ME;Trompet S;Arias-Vasquez A;Seshadri S;Desrivières S;Beecham AH;Jahanshad N;Wittfeld K;Van der Lee SJ;Abramovic L;Alhusaini S;Amin N;Andersson M;Arfanakis K;Aribisala BS;Armstrong NJ;Athanasiu L;Axelsson T;Beiser A;Bernard M;Bis JC;Blanken LM;Blanton SH;Bohlken MM;Boks MP;Bralten J;Brickman AM;Carmichael O;Chakravarty MM;Chauhan G;Chen Q;Ching CR;Cuellar-Partida G;Braber AD;Doan NT;Ehrlich S;Filippi I;Ge T;Giddaluru S;Goldman AL;Gottesman RF;Greven CU;Grimm O;Griswold ME;Guadalupe T;Hass J;Haukvik UK;Hilal S;Hofer E;Hoehn D;Holmes AJ;Hoogman M;Janowitz D;Jia T;Kasperaviciute D;Kim S;Klein M;Kraemer B;Lee PH;Liao J;Liewald DC;Lopez LM;Luciano M;Macare C;Marquand A;Matarin M;Mather KA;Mattheisen M;Mazoyer B;McKay DR;McWhirter R;Milaneschi Y;Mirza-Schreiber N;Muetzel RL;Maniega SM;Nho K;Nugent AC;Loohuis LM;Oosterlaan J;Papmeyer M;Pappa I;Pirpamer L;Pudas S;Pütz B;Rajan KB;Ramasamy A;Richards JS;Risacher SL;Roiz-Santiañez R;Rommelse N;Rose EJ;Royle NA;Rundek T;Sämann PG;Satizabal CL;Schmaal L;Schork AJ;Shen L;Shin J;Shumskaya E;Smith AV;Sprooten E;Strike LT;Teumer A;Thomson R;Tordesillas-Gutierrez D;Toro R;Trabzuni D;Vaidya D;Van der Grond J;Van der Meer D;Van Donkelaar MM;Van Eijk KR;Van Erp TG;Van Rooij D;Walton E;Westlye LT;Whelan CD;Windham BG;Winkler AM;Woldehawariat G;Wolf C;Wolfers T;Xu B;Yanek LR;Yang J;Zijdenbos A;Zwiers MP;Agartz I;Aggarwal NT;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;Chen C;Cheng CY;Cichon S;Cookson MR;Corvin A;Crespo-Facorro B;Curran JE;Czisch M;Dale AM;Davies GE;De Geus EJ;De Jager PL;de Zubicaray GI;Delanty N;Depondt C;DeStefano AL;Dillman A;Djurovic S;Donohoe G;Drevets WC;Duggirala R;Dyer TD;Erk S;Espeseth T;Evans DA;Fedko IO;Fernández G;Ferrucci L;Fisher SE;Fleischman DA;Ford I;Foroud TM;Fox PT;Francks C;Fukunaga M;Gibbs JR;Glahn DC;Gollub RL;Göring HH;Grabe HJ;Green RC;Gruber O;Gudnason V;Guelfi S;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;Hulshoff Pol HE;Ikeda M;Ikram MK;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;Longstreth WT Jr;Lopez OL;Lovestone S;Martinez O;Martinot JL;Mattay VS;McDonald C;McIntosh AM;McMahon KL;McMahon FJ;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 BW;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;Schofield PR;Sigurdsson S;Simmons A;Singleton A;Sisodiya SM;Smith C;Smoller JW;Soininen H;Srikanth V;Steen VM;Stott DJ;Sussmann JE;Thalamuthu A;Tiemeier H;Toga AW;Traynor BJ;Troncoso J;Turner JA;Tzourio C;Uitterlinden AG;Hernández MC;Van der Brug M;Van der Lugt A;Van der Wee NJ;Van Duijn CM;Van Haren NE;Van T Ent D;Van Tol MJ;Vardarajan BN;Veltman DJ;Vernooij MW;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 HR;Zonderman AB;Deary IJ;DeCarli C;Schmidt H;Martin NG;De Craen AJ;Wright MJ;Launer LJ;Schumann G;Fornage M;Franke B;Debette S;Medland SE;Ikram MA;Thompson PM
颅内体积反映了发育过程中获得的最大脑体积，并在晚年随着组织损失而保持稳定。它是高度遗传的，但潜在的基因仍然在很大程度上不确定。在对32，438名成年人进行的全基因组关联研究中，我们发现了五个新的颅内体积位点，并确认了两个已知信号。四个位点也与成人身高相关，但在调整身高后，这些位点仍与颅内体积相关。我们发现与儿童头围有很高的遗传相关性（ρgenetic=0.748），这表明了相似的遗传背景，并允许通过荟萃分析（Ncombined = 37，345）识别出另外四个基因座。颅内体积的变异体也与儿童和成人认知功能、帕金森病有关，并富集了参与生长途径（包括PI 3 K-AKT信号传导）的近基因。这些发现确定了颅内容量的生物学基础，并为脑储备和脑过度生长的理论提供了遗传学支持。
Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five novel loci for intracranial volume and confirmed two known signals. Four of the loci are also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρgenetic=0.748), which indicated a similar genetic background and allowed for the identification of four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, Parkinson’s disease, and enriched near genes involved in growth pathways including PI3K–AKT signaling. These findings identify biological underpinnings of intracranial volume and provide genetic support for theories on brain reserve and brain overgrowth.