Genetic correlations and genome-wide associations of cortical structure in general population samples of 22,824 adults.
Hofer E., Roshchupkin GV., Adams HHH., Knol MJ., Lin H., Li S., Zare H., Ahmad S., Armstrong NJ., Satizabal CL., Bernard M., Bis JC., Gillespie NA., Luciano M., Mishra A., Scholz M., Teumer A., Xia R., Jian X., Mosley TH., Saba Y., Pirpamer L., Seiler S., Becker JT., Carmichael O., Rotter JI., Psaty BM., Lopez OL., Amin N., van der Lee SJ., Yang Q., Himali JJ., Maillard P., Beiser AS., DeCarli C., Karama S., Lewis L., Harris M., Bastin ME., Deary IJ., Veronica Witte A., Beyer F., Loeffler M., Mather KA., Schofield PR., Thalamuthu A., Kwok JB., Wright MJ., Ames D., Trollor J., Jiang J., Brodaty H., Wen W., Vernooij MW., Hofman A., Uitterlinden AG., Niessen WJ., Wittfeld K., Bülow R., Völker U., Pausova Z., Bruce Pike G., Maingault S., Crivello F., Tzourio C., Amouyel P., Mazoyer B., Neale MC., Franz CE., Lyons MJ., Panizzon MS., Andreassen OA., Dale AM., Logue M., Grasby KL., Jahanshad N., Painter JN., Colodro-Conde L., Bralten J., Hibar DP., Lind PA., Pizzagalli F., Stein JL., Thompson PM., Medland SE., ENIGMA consortium None., Sachdev PS., Kremen WS., Wardlaw JM., Villringer A., van Duijn CM., Grabe HJ., Longstreth WT., Fornage M., Paus T., Debette S., Arfan Ikram M., Schmidt H., Schmidt R., Seshadri S.
Cortical thickness, surface area and volumes vary with age and cognitive function, and in neurological and psychiatric diseases. Here we report heritability, genetic correlations and genome-wide associations of these cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprises 22,824 individuals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank. We identify genetic heterogeneity between cortical measures and brain regions, and 160 genome-wide significant associations pointing to wnt/β-catenin, TGF-β and sonic hedgehog pathways. There is enrichment for genes involved in anthropometric traits, hindbrain development, vascular and neurodegenerative disease and psychiatric conditions. These data are a rich resource for studies of the biological mechanisms behind cortical development and aging.