Novel genetic loci associated with hippocampal volume
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 C-Y., 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 B-C., Hoekstra PJ., Hoffmann W., Hofman A., Holsboer F., Homuth G., Hosten N., Hottenga J-J., Huentelman M., Hulshoff Pol HE., Ikeda M., Jack Jr CR., 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 J-L., 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 M-J., 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.
AbstractThe 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.