Genetic correlations and genome-wide associations of cortical structure in general population samples of 22,824 adults

Edith Hofer,Reinhold Schmidt,Geneviève Richard,Sarah E Medland,Mark Logue,Tomáš Paus,Dag Alnæs,Inge K Amlien,Anders M Dale,Cornelia M Van Duijn,Shahzad Ahmad,Saud Alhusaini,Marcio Almeida ,Nhat Trung Doan,Thomas Espeseth,Paul M Thompson,Srdjan Djurovic,Christine Lycke Brandt ,M Arfan Ikram,Ingrid Melle,W T Longstreth ,Knut-Kristian Kolskår ,Vidar M Steen,Katrina L Grasby,Maria J Knol,Ida Elken Sønderby ,Jan Egil Nordvik ,Yunpeng Wang,Matthew S Panizzon,Asta Håberg ,Claudia L Satizábal ,Dennis Van Der Meer,Margaret J Wright,Hans J Grabe,Dan J Stein,Sudha Seshadri,Stéphanie Debette ,Gennady V Roshchupkin,Juan Zhou,Lars T Westlye,Hieab H.h Adams ,Habil Zare,Tiril P Gurholt,Ole A Andreassen,Tobias Kaufmann,Shuo Li,Ingrid Agartz,Honghuang Lin,Nicola J Armstrong,Myriam Fornage,Helena Schmidt

doi:10.1038/s41467-020-18367-y

Abstract

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.

Highlights

Cortical thickness, surface area and volumes vary with age and cognitive function, and in neurological and psychiatric diseases
Neurons in the neocortex are organized in columns which run perpendicular to the surface of the cerebral cortex[12]; and, according to the radial unit hypothesis, cortical thickness (CTh) is determined by the number of cells within the columns and cortical surface area (CSA) is determined by the number of columns[13]
We observe genetic heterogeneity between cortical measures and brain regions and find enrichment for genes involved in anthropometric traits, hindbrain development, vascular and neurodegenerative disease, and psychiatric conditions

Summary

Introduction

Surface area and volumes vary with age and cognitive function, and in neurological and psychiatric diseases. 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. Brain cortical thickness (CTh), cortical surface area (CSA), and cortical volume (CV) are morphological markers of cortical structure obtained from magnetic resonance imaging (MRI) These measures change with age[1,2,3] and are linked to cognitive functioning[4,5]. We observe genetic heterogeneity between cortical measures and brain regions and find enrichment for genes involved in anthropometric traits, hindbrain development, vascular and neurodegenerative disease, and psychiatric conditions

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Conclusion