Common genetic variants influence human subcortical brain structures.
Hibar DP., Stein JL., Renteria ME., Arias-Vasquez A., Desrivières S., Jahanshad N., Toro R., Wittfeld K., Abramovic L., Andersson M., Aribisala BS., Armstrong NJ., Bernard M., Bohlken MM., Boks MP., Bralten J., Brown AA., Chakravarty MM., Chen Q., Ching CRK., Cuellar-Partida G., den Braber A., Giddaluru S., Goldman AL., Grimm O., Guadalupe T., Hass J., Woldehawariat G., Holmes AJ., Hoogman M., Janowitz D., Jia T., Kim S., Klein M., Kraemer B., Lee PH., Olde Loohuis LM., Luciano M., Macare C., Mather KA., Mattheisen M., Milaneschi Y., Nho K., Papmeyer M., Ramasamy A., Risacher SL., Roiz-Santiañez R., Rose EJ., Salami A., Sämann PG., Schmaal L., Schork AJ., Shin J., Strike LT., Teumer A., van Donkelaar MMJ., van Eijk KR., Walters RK., Westlye LT., Whelan CD., Winkler AM., Zwiers MP., Alhusaini S., Athanasiu L., Ehrlich S., Hakobjan MMH., Hartberg CB., Haukvik UK., Heister AJGAM., Hoehn D., Kasperaviciute D., Liewald DCM., Lopez LM., Makkinje RRR., Matarin M., Naber MAM., McKay DR., Needham M., Nugent AC., Pütz B., Royle NA., Shen L., Sprooten E., Trabzuni D., van der Marel SSL., van Hulzen KJE., Walton E., Wolf C., Almasy L., Ames D., Arepalli S., Assareh AA., Bastin ME., Brodaty H., Bulayeva KB., Carless MA., Cichon S., Corvin A., Curran JE., Czisch M., de Zubicaray GI., Dillman A., Duggirala R., Dyer TD., Erk S., Fedko IO., Ferrucci L., Foroud TM., Fox PT., Fukunaga M., Gibbs JR., Göring HHH., Green RC., Guelfi S., Hansell NK., Hartman CA., Hegenscheid K., Heinz A., Hernandez DG., Heslenfeld DJ., Hoekstra PJ., Holsboer F., Homuth G., Hottenga J-J., Ikeda M., Jack CR., Jenkinson M., Johnson R., Kanai R., Keil M., Kent JW., Kochunov P., Kwok JB., Lawrie SM., Liu X., Longo DL., McMahon KL., Meisenzahl E., Melle I., Mohnke S., Montgomery GW., Mostert JC., Mühleisen TW., Nalls MA., Nichols TE., Nilsson LG., Nöthen MM., Ohi K., Olvera RL., Perez-Iglesias R., Pike GB., Potkin SG., Reinvang I., Reppermund S., Rietschel M., Romanczuk-Seiferth N., Rosen GD., Rujescu D., Schnell K., Schofield PR., Smith C., Steen VM., Sussmann JE., Thalamuthu A., Toga AW., Traynor BJ., Troncoso J., Turner JA., Valdés Hernández MC., van 't Ent D., van der Brug M., van der Wee NJA., van Tol M-J., Veltman DJ., Wassink TH., Westman E., Zielke RH., Zonderman AB., Ashbrook DG., Hager R., Lu L., McMahon FJ., Morris DW., Williams RW., Brunner HG., Buckner RL., Buitelaar JK., Cahn W., Calhoun VD., Cavalleri GL., Crespo-Facorro B., Dale AM., Davies GE., Delanty N., Depondt C., Djurovic S., Drevets WC., Espeseth T., Gollub RL., Ho B-C., Hoffmann W., Hosten N., Kahn RS., Le Hellard S., Meyer-Lindenberg A., Müller-Myhsok B., Nauck M., Nyberg L., Pandolfo M., Penninx BWJH., Roffman JL., Sisodiya SM., Smoller JW., van Bokhoven H., van Haren NEM., Völzke H., Walter H., Weiner MW., Wen W., White T., Agartz I., Andreassen OA., Blangero J., Boomsma DI., Brouwer RM., Cannon DM., Cookson MR., de Geus EJC., Deary IJ., Donohoe G., Fernández G., Fisher SE., Francks C., Glahn DC., Grabe HJ., Gruber O., Hardy J., Hashimoto R., Hulshoff Pol HE., Jönsson EG., Kloszewska I., Lovestone S., Mattay VS., Mecocci P., McDonald C., McIntosh AM., Ophoff RA., Paus T., Pausova Z., Ryten M., Sachdev PS., Saykin AJ., Simmons A., Singleton A., Soininen H., Wardlaw JM., Weale ME., Weinberger DR., Adams HHH., Launer LJ., Seiler S., Schmidt R., Chauhan G., Satizabal CL., Becker JT., Yanek L., van der Lee SJ., Ebling M., Fischl B., Longstreth WT., Greve D., Schmidt H., Nyquist P., Vinke LN., van Duijn CM., Xue L., Mazoyer B., Bis JC., Gudnason V., Seshadri S., Ikram MA., Alzheimer’s Disease Neuroimaging Initiative None., CHARGE Consortium None., EPIGEN None., IMAGEN None., SYS None., Martin NG., Wright MJ., Schumann G., Franke B., Thompson PM., Medland SE.
The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume and intracranial volume. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.