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Meta-Analysis
. 2020 Sep 22;11(1):4796.
doi: 10.1038/s41467-020-18367-y.

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

Edith Hofer #  1   2 , Gennady V Roshchupkin #  3   4   5 , Hieab H H Adams #  3   5 , Maria J Knol  5 , Honghuang Lin  6 , Shuo Li  7 , Habil Zare  8   9 , Shahzad Ahmad  5 , Nicola J Armstrong  10 , Claudia L Satizabal  8   11 , Manon Bernard  12 , Joshua C Bis  13 , Nathan A Gillespie  14   15 , Michelle Luciano  16   17 , Aniket Mishra  18 , Markus Scholz  19   20 , Alexander Teumer  21 , Rui Xia  22 , Xueqiu Jian  22 , Thomas H Mosley  23 , Yasaman Saba  24 , Lukas Pirpamer  1 , Stephan Seiler  25   26 , James T Becker  27 , Owen Carmichael  28 , Jerome I Rotter  29 , Bruce M Psaty  13 , Oscar L Lopez  27 , Najaf Amin  5 , Sven J van der Lee  5 , Qiong Yang  7 , Jayandra J Himali  7 , Pauline Maillard  25   26 , Alexa S Beiser  7   11 , Charles DeCarli  25   26 , Sherif Karama  30 , Lindsay Lewis  30 , Mat Harris  16   31   32   33 , Mark E Bastin  16   31   32   33 , Ian J Deary  16   17 , A Veronica Witte  34   35 , Frauke Beyer  34   35 , Markus Loeffler  19   20 , Karen A Mather  36   37 , Peter R Schofield  37   38 , Anbupalam Thalamuthu  36 , John B Kwok  38   39 , Margaret J Wright  40   41 , David Ames  42   43 , Julian Trollor  36   44 , Jiyang Jiang  36 , Henry Brodaty  36   45 , Wei Wen  36 , Meike W Vernooij  3   5 , Albert Hofman  5   46 , André G Uitterlinden  5 , Wiro J Niessen  3   47 , Katharina Wittfeld  48   49 , Robin Bülow  50 , Uwe Völker  51 , Zdenka Pausova  12   52 , G Bruce Pike  53 , Sophie Maingault  54 , Fabrice Crivello  54 , Christophe Tzourio  18   55 , Philippe Amouyel  56   57   58 , Bernard Mazoyer  54 , Michael C Neale  14 , Carol E Franz  59 , Michael J Lyons  60 , Matthew S Panizzon  59 , Ole A Andreassen  61 , Anders M Dale  62 , Mark Logue  7   63   64 , Katrina L Grasby  65 , Neda Jahanshad  66 , Jodie N Painter  65 , Lucía Colodro-Conde  65 , Janita Bralten  67   68 , Derrek P Hibar  66   69 , Penelope A Lind  65 , Fabrizio Pizzagalli  66 , Jason L Stein  70 , Paul M Thompson  66 , Sarah E Medland  65 ; ENIGMA consortium; Perminder S Sachdev  36   71 , William S Kremen  59 , Joanna M Wardlaw  16   31   32   33 , Arno Villringer  34   72 , Cornelia M van Duijn  5   73 , Hans J Grabe  48   49 , William T Longstreth Jr  74 , Myriam Fornage  22 , Tomas Paus  75   76 , Stephanie Debette  11   18   77 , M Arfan Ikram  3   5   78 , Helena Schmidt  24 , Reinhold Schmidt  79 , Sudha Seshadri  80   81
Collaborators, Affiliations
Meta-Analysis

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

Edith Hofer et al. Nat Commun. .

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.

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Conflict of interest statement

Dr. Dale is a founder of and holds equity in CorTechs Labs, Inc, and serves on its Scientific Advisory Board. He is a member of the Scientific Advisory Board of Human Longevity, Inc. and receives funding through research agreements with General Electric Healthcare and Medtronic, Inc. The terms of these arrangements have been reviewed and approved by UCSD in accordance with its conflict of interest policies. W. Niessen is co-founder and shareholder of Quantib BV. H. Brodaty is an advisory board member of Nutricia. The other authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Chromosomal ideogram of genome-wide significant associations with measures of cortical structure.
Cortical surface areas, cortical volumes and cortical thickness. Each point represents the significantly associated variant, the colors correspond to the different cortical regions and the shape to different type of measument (pDiscovery < 1.09 × 10−9).
Fig. 2
Fig. 2. Lowest discovery meta-analysis p-value of CSA, CTh, and CV in each cortical region.
a Lowest pDiscovery of CSA, b lowest pDiscovery of CTh, c lowest pDiscovery of CV.
Fig. 3
Fig. 3. Functional annotation categories for global and regional CTh, CSA, and CV.
Proportion of functional annotation categories for global and regional cortical thickness (blue), surface area (light green), and volume (yellow) assigned by ANNOVAR.
Fig. 4
Fig. 4. Number of overlapping genes between gene mapping methods.
Number of overlapping genes between FUMA eQTL mapping, FUMA chromatin interaction mapping, ANNOVAR chromosome positional mapping, and MAGMA gene-based analysis for all cortical regions combined for cortical surface area (a), thickness (b) and volume (c).
See this image and copyright information in PMC

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