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

TitleGenetic correlations and genome-wide associations of cortical structure in general population samples of 22,824 adults.
Publication TypeJournal Article
Year of Publication2020
AuthorsHofer 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, A Witte V, 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, G Pike B, 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, Sachdev PS, Kremen WS, Wardlaw JM, Villringer A, van Duijn CM, Grabe HJ, Longstreth WT, Fornage M, Paus T, Debette S, M Ikram A, Schmidt H, Schmidt R, Seshadri S
Corporate AuthorsENIGMA Consortium
JournalNat Commun
Volume11
Issue1
Pagination4796
Date Published2020 09 22
ISSN2041-1723
KeywordsAdult, Aged, Aged, 80 and over, Aging, Brain, Chromosome Structures, Cognition, Female, Genome-Wide Association Study, Genomics, Humans, Male, Mental Disorders, Middle Aged, Neurodegenerative Diseases, Phenotype, Polymorphism, Single Nucleotide
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.

DOI10.1038/s41467-020-18367-y
Alternate JournalNat Commun
PubMed ID32963231
PubMed Central IDPMC7508833
Grant ListHHSN268201100008C / HL / NHLBI NIH HHS / United States
75N92019D00031 / HL / NHLBI NIH HHS / United States
N01HC55222 / HL / NHLBI NIH HHS / United States
N01HC25195 / HL / NHLBI NIH HHS / United States
HHSN268201100009C / HL / NHLBI NIH HHS / United States
N01HC85081 / HL / NHLBI NIH HHS / United States
R01 AG054076 / AG / NIA NIH HHS / United States
P41 EB015922 / EB / NIBIB NIH HHS / United States
N01HC85080 / HL / NHLBI NIH HHS / United States
P30 AG010129 / AG / NIA NIH HHS / United States
MR/K026992/1 / MRC_ / Medical Research Council / United Kingdom
MR/M01311/1 / MRC_ / Medical Research Council / United Kingdom
G1001401 / MRC_ / Medical Research Council / United Kingdom
TMH109788 / / CIHR / Canada
BB/F019394/1 / BB_ / Biotechnology and Biological Sciences Research Council / United Kingdom
R01 AG023629 / AG / NIA NIH HHS / United States
HHSN268201800001C / HL / NHLBI NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
HHSN268201100007C / HL / NHLBI NIH HHS / United States
R01 HL120393 / HL / NHLBI NIH HHS / United States
R01 EB015611 / EB / NIBIB NIH HHS / United States
HHSN268201200036C / HL / NHLBI NIH HHS / United States
RC2 HL102419 / HL / NHLBI NIH HHS / United States
R01 NS087541 / NS / NINDS NIH HHS / United States
MC_QA137853 / MRC_ / Medical Research Council / United Kingdom
R01 HL103612 / HL / NHLBI NIH HHS / United States
R01 AG049607 / AG / NIA NIH HHS / United States
HHSN268201100011C / HL / NHLBI NIH HHS / United States
U01 HL130114 / HL / NHLBI NIH HHS / United States
MR/M013111/1 / MRC_ / Medical Research Council / United Kingdom
G1001245 / MRC_ / Medical Research Council / United Kingdom
MR/R024065/1 / MRC_ / Medical Research Council / United Kingdom
N01HC85082 / HL / NHLBI NIH HHS / United States
U54 EB020403 / EB / NIBIB NIH HHS / United States
NET54015 / / CIHR / Canada
N02 HL64278 / HL / NHLBI NIH HHS / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States
HHSN268201500001I / HL / NHLBI NIH HHS / United States
MR/N027558/1 / MRC_ / Medical Research Council / United Kingdom
N01HC85079 / HL / NHLBI NIH HHS / United States
N01HC85083 / HL / NHLBI NIH HHS / United States
N01HC85086 / HL / NHLBI NIH HHS / United States
G0701120 / MRC_ / Medical Research Council / United Kingdom
R01 AG033040 / AG / NIA NIH HHS / United States
HHSN268201100012C / HL / NHLBI NIH HHS / United States
R01 AG016495 / AG / NIA NIH HHS / United States
HHSN268201100005C / HL / NHLBI NIH HHS / United States
R01 MH117601 / MH / NIMH NIH HHS / United States
R01 AG033193 / AG / NIA NIH HHS / United States
U01 AG049505 / AG / NIA NIH HHS / United States
RF1 AG051710 / AG / NIA NIH HHS / United States
R01 AG059874 / AG / NIA NIH HHS / United States
G0700704 / MRC_ / Medical Research Council / United Kingdom
R01 HL087652 / HL / NHLBI NIH HHS / United States
HHSN268201100006C / HL / NHLBI NIH HHS / United States
MC_PC_17228 / MRC_ / Medical Research Council / United Kingdom
HHSN268200800007C / HL / NHLBI NIH HHS / United States
S10 OD023696 / OD / NIH HHS / United States
UL1 TR001881 / TR / NCATS NIH HHS / United States
R01 NS017950 / NS / NINDS NIH HHS / United States
G0700704/84698 / MRC_ / Medical Research Council / United Kingdom
NRF86678 / / CIHR / Canada
R01 MH116147 / MH / NIMH NIH HHS / United States
HHSN268201100010C / HL / NHLBI NIH HHS / United States
R01 AG008122 / AG / NIA NIH HHS / United States
RF1 AG041915 / AG / NIA NIH HHS / United States
R01 AG022381 / AG / NIA NIH HHS / United States
R01 AG050595 / AG / NIA NIH HHS / United States
8200 / MRC_ / Medical Research Council / United Kingdom
P01 AG026572 / AG / NIA NIH HHS / United States