title: Heritability of the shape of subcortical brain structures in the general population.
abstract: The volumes of subcortical brain structures are highly heritable, but genetic underpinnings of their shape remain relatively obscure. Here we determine the relative contribution of genetic factors to individual variation in the shape of seven bilateral subcortical structures: the nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen and thalamus. In 3,686 unrelated individuals aged between 45 and 98 years, brain magnetic resonance imaging and genotyping was performed. The maximal heritability of shape varies from 32.7 to 53.3% across the subcortical structures. Genetic contributions to shape extend beyond influences on intracranial volume and the gross volume of the respective structure. The regional variance in heritability was related to the reliability of the measurements, but could not be accounted for by technical factors only. These findings could be replicated in an independent sample of 1,040 twins. Differences in genetic contributions within a single region reveal the value of refined brain maps to appreciate the genetic complexity of brain structures.
authors.affiliation: Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam 3015 CE, The Netherlands.|Department of Medical Informatics, Erasmus MC, Rotterdam 3015 CE, The Netherlands.
authors.forename: Gennady V
authors.identifier: http://orcid.org/0000-0002-3403-2313
authors.initials: GV
authors.lastname: Roshchupkin
authors.affiliation: Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of the University of Southern California, Marina del ReyLos Angeles, California 90292, USA.
authors.forename: Boris A
authors.initials: BA
authors.lastname: Gutman
authors.affiliation: Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam 3015 CE, The Netherlands.|Department of Epidemiology, Erasmus MC, Rotterdam 3015 CE, The Netherlands.
authors.forename: Meike W
authors.initials: MW
authors.lastname: Vernooij
authors.affiliation: Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of the University of Southern California, Marina del ReyLos Angeles, California 90292, USA.
authors.forename: Neda
authors.initials: N
authors.lastname: Jahanshad
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006, Australia.
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Martin
authors.affiliation: Department of Epidemiology, Erasmus MC, Rotterdam 3015 CE, The Netherlands.|Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115, USA.
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.affiliation: Centre for Advanced Imaging, The University of Queensland, Brisbane, Queensland 4072, Australia.
authors.forename: Katie L
authors.initials: KL
authors.lastname: McMahon
authors.affiliation: Department of Epidemiology, Erasmus MC, Rotterdam 3015 CE, The Netherlands.
authors.forename: Sven J
authors.identifier: http://orcid.org/0000-0003-1606-8643
authors.initials: SJ
authors.lastname: van der Lee
authors.affiliation: Department of Epidemiology, Erasmus MC, Rotterdam 3015 CE, The Netherlands.|Translational Epidemiology, Faculty Science, Leiden University, Leiden, 2333 CC, The Netherlands.
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: van Duijn
authors.affiliation: Faculty of Health, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland 4059, Australia.
authors.forename: Greig I
authors.initials: GI
authors.lastname: de Zubicaray
authors.affiliation: Department of Internal Medicine, Erasmus MC, Rotterdam 3015 CE, The Netherlands.
authors.forename: André G
authors.initials: AG
authors.lastname: Uitterlinden
authors.affiliation: Centre for Advanced Imaging, The University of Queensland, Brisbane, Queensland 4072, Australia.|Queensland Brain Institute, The University of Queensland, Brisbane, Queensland 4072, Australia.
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Wright
authors.affiliation: Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam 3015 CE, The Netherlands.|Department of Medical Informatics, Erasmus MC, Rotterdam 3015 CE, The Netherlands.|Faculty of Applied Sciences, Delft University of Technology, Delft 2628 CJ, The Netherlands.
authors.forename: Wiro J
authors.initials: WJ
authors.lastname: Niessen
authors.affiliation: Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of the University of Southern California, Marina del ReyLos Angeles, California 90292, USA.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Thompson
authors.affiliation: Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam 3015 CE, The Netherlands.|Department of Epidemiology, Erasmus MC, Rotterdam 3015 CE, The Netherlands.|Department of Neurology, Erasmus MC, Rotterdam 3015 CE, The Netherlands.
authors.forename: M Arfan
authors.initials: MA
authors.lastname: Ikram
authors.affiliation: Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam 3015 CE, The Netherlands.|Department of Epidemiology, Erasmus MC, Rotterdam 3015 CE, The Netherlands.
authors.forename: Hieab H H
authors.initials: HHH
authors.lastname: Adams
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000679:Amygdala / Q000033:anatomy & histology / Q000000981:diagnostic imaging; D001921:Brain / Q000033:anatomy & histology* / Q000000981:diagnostic imaging; D002421:Caudate Nucleus / Q000033:anatomy & histology / Q000000981:diagnostic imaging; D005260:Female; D005838:Genotype; D005917:Globus Pallidus / Q000033:anatomy & histology / Q000000981:diagnostic imaging; D006624:Hippocampus / Q000033:anatomy & histology / Q000000981:diagnostic imaging; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009714:Nucleus Accumbens / Q000033:anatomy & histology / Q000000981:diagnostic imaging; D009929:Organ Size / Q000235:genetics*; D011699:Putamen / Q000000981:diagnostic imaging / Q000502:physiology; D015203:Reproducibility of Results; D013788:Thalamus / Q000033:anatomy & histology / Q000000981:diagnostic imaging; D014429:Twins, Dizygotic / Q000235:genetics*; D014430:Twins, Monozygotic / Q000235:genetics*; D055815:Young Adult