TY - JOUR
T1 - Genetic control of variability in subcortical and intracranial volumes
AU - Cordova-Palomera, Aldo
AU - van der Meer, Dennis
AU - Kaufmann, Tobias
AU - Bettella, Francesco
AU - Wang, Yunpeng
AU - Alnaes, Dag
AU - Nhat Trung Doan, null
AU - Agartz, Ingrid
AU - Bertolino, Alessandro
AU - Buitelaar, Jan K.
AU - Coynel, David
AU - Djurovic, Srdjan
AU - Dorum, Erlend S.
AU - Espeseth, Thomas
AU - Fazio, Leonardo
AU - Franke, Barbara
AU - Frei, Oleksandr
AU - Haberg, Asta
AU - Le Hellard, Stephanie
AU - Jonsson, Erik G.
AU - Kolskar, Knut K.
AU - Lund, Martina J.
AU - Moberget, Torgeir
AU - Nordvik, Jan E.
AU - Nyberg, Lars
AU - Papassotiropoulos, Andreas
AU - Pergola, Giulio
AU - de Quervain, Dominique
AU - Rampino, Antonio
AU - Richard, Genevieve
AU - Rokicki, Jaroslav
AU - Sanders, Anne-Marthe
AU - Schwarz, Emanuel
AU - Smeland, Olav B.
AU - Steen, Vidar M.
AU - Starrfelt, Jostein
AU - Sonderby, Ida E.
AU - Ulrichsen, Kristine M.
AU - Andreassen, Ole A.
AU - Westlye, Lars T.
PY - 2021/8
Y1 - 2021/8
N2 - Sensitivity to external demands is essential for adaptation to dynamic environments, but comes at the cost of increased risk of adverse outcomes when facing poor environmental conditions. Here, we apply a novel methodology to perform genome-wide association analysis of mean and variance in ten key brain features (accumbens, amygdala, caudate, hippocampus, pallidum, putamen, thalamus, intracranial volume, cortical surface area, and cortical thickness), integrating genetic and neuroanatomical data from a large lifespan sample (n = 25,575 individuals; 8-89 years, mean age 51.9 years). We identify genetic loci associated with phenotypic variability in thalamus volume and cortical thickness. The variance-controlling loci involved genes with a documented role in brain and mental health and were not associated with the mean anatomical volumes. This proof-of-principle of the hypothesis of a genetic regulation of brain volume variability contributes to establishing the genetic basis of phenotypic variance (i.e., heritability), allows identifying different degrees of brain robustness across individuals, and opens new research avenues in the search for mechanisms controlling brain and mental health.
AB - Sensitivity to external demands is essential for adaptation to dynamic environments, but comes at the cost of increased risk of adverse outcomes when facing poor environmental conditions. Here, we apply a novel methodology to perform genome-wide association analysis of mean and variance in ten key brain features (accumbens, amygdala, caudate, hippocampus, pallidum, putamen, thalamus, intracranial volume, cortical surface area, and cortical thickness), integrating genetic and neuroanatomical data from a large lifespan sample (n = 25,575 individuals; 8-89 years, mean age 51.9 years). We identify genetic loci associated with phenotypic variability in thalamus volume and cortical thickness. The variance-controlling loci involved genes with a documented role in brain and mental health and were not associated with the mean anatomical volumes. This proof-of-principle of the hypothesis of a genetic regulation of brain volume variability contributes to establishing the genetic basis of phenotypic variance (i.e., heritability), allows identifying different degrees of brain robustness across individuals, and opens new research avenues in the search for mechanisms controlling brain and mental health.
KW - SCHIZOPHRENIA
KW - ROBUSTNESS
U2 - 10.1038/s41380-020-0664-1
DO - 10.1038/s41380-020-0664-1
M3 - Article
C2 - 32047264
SN - 1359-4184
VL - 26
SP - 3876
EP - 3883
JO - Molecular Psychiatry
JF - Molecular Psychiatry
IS - 8
ER -