Heritability of fractional anisotropy in human white matter: a comparison of Human Connectome Project and ENIGMA-DTI data.
The degree to which genetic factors influence brain connectivity is beginning to be understood. Large-scale efforts are underway to map the profile of genetic effects in various brain regions. The NIH-funded Human Connectome Project (HCP) is providing data valuable for analyzing the degree of genetic influence underlying brain connectivity revealed by state-of-the-art neuroimaging methods. We calculated the heritability of the fractional anisotropy (FA) measure derived from diffusion tensor imaging (DTI) reconstruction in 481 HCP subjects (194/287 M/F) consisting of 57/60 pairs of mono- and dizygotic twins, and 246 siblings. FA measurements were derived using (Enhancing NeuroImaging Genetics through Meta-Analysis) ENIGMA DTI protocols and heritability estimates were calculated using the SOLAR-Eclipse imaging genetic analysis package. We compared heritability estimates derived from HCP data to those publicly available through the ENIGMA-DTI consortium, which were pooled together from five-family based studies across the US, Europe, and Australia. FA measurements from the HCP cohort for eleven major white matter tracts were highly heritable (h(2)=0.53-0.90, p<10(-5)), and were significantly correlated with the joint-analytical estimates from the ENIGMA cohort on the tract and voxel-wise levels. The similarity in regional heritability suggests that the additive genetic contribution to white matter microstructure is consistent across populations and imaging acquisition parameters. It also suggests that the overarching genetic influence provides an opportunity to define a common genetic search space for future gene-discovery studies. Uniquely, the measurements of additive genetic contribution performed in this study can be repeated using online genetic analysis tools provided by the HCP ConnectomeDB web application.
Maryland Psychiatric Research Center, University of MD School of Medicine, Baltimore USA. Electronic address: pkochunov@mprc.umaryland.edu.
Peter
P
Kochunov
Imaging Genetics Center, Institute for Neuroimaging and Informatics, Department of Neurology Keck School of Medicine, University of Southern CA, Marina del Rey, USA.
Neda
N
Jahanshad
Department of Radiology, Washington University School of Medicine, St. Louis, USA.
Daniel
D
Marcus
FMRIB Centre, Oxford University, Oxford, UK.
Anderson
A
Winkler
Olin Neuropsychiatry Research Center, Institute of Living, Hartford Hospital, Hartford, USA.
Emma
E
Sprooten
Department of Statistics, University of Warwick, Warwick, UK.
Thomas E
TE
Nichols
Maryland Psychiatric Research Center, University of MD School of Medicine, Baltimore USA.
Susan N
SN
Wright
Maryland Psychiatric Research Center, University of MD School of Medicine, Baltimore USA.
L Elliot
LE
Hong
Maryland Psychiatric Research Center, University of MD School of Medicine, Baltimore USA.
Binish
B
Patel
FMRIB Centre, Oxford University, Oxford, UK.
Timothy
T
Behrens
FMRIB Centre, Oxford University, Oxford, UK.
Saad
S
Jbabdi
FMRIB Centre, Oxford University, Oxford, UK.
Jesper
J
Andersson
Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota Medical School, Minneapolis, MN, USA.
Christophe
C
Lenglet
Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota Medical School, Minneapolis, MN, USA.
Essa
E
Yacoub
Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota Medical School, Minneapolis, MN, USA.
Steen
S
Moeller
Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota Medical School, Minneapolis, MN, USA.
Eddie
E
Auerbach
Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota Medical School, Minneapolis, MN, USA.
Kamil
K
Ugurbil
FMRIB Centre, Oxford University, Oxford, UK.
Stamatios N
SN
Sotiropoulos
University Medical Center Utrecht, Utrecht, The Netherlands.
Rachel M
RM
Brouwer
Vanderbilt University, Nashville, TN, USA.
Bennett
B
Landman
INSERM-CEA-Faculté de Médecine Paris-Sud, Orsay France.
Hervé
H
Lemaitre
VU University, Amsterdam, The Netherlands.
Anouk
A
den Braber
Radboud University, Nijmegen, The Netherlands.
Marcel P
MP
Zwiers
University of Edinburgh, Edinburgh, UK.
Stuart
S
Ritchie
Radboud University, Nijmegen, The Netherlands.
Kimm
K
van Hulzen
Texas Biomedical Research Institute, San Antonio, TX, USA.
Laura
L
Almasy
Texas Biomedical Research Institute, San Antonio, TX, USA.
Joanne
J
Curran
University of Queensland, Brisbane, Australia.
Greig I
GI
deZubicaray
Texas Biomedical Research Institute, San Antonio, TX, USA.
Ravi
R
Duggirala
University of Texas Health Science Center San Antonio, San Antonio, TX, USA.
Peter
P
Fox
QIMR Berghofer, Brisbane, Australia.
Nicholas G
NG
Martin
University of Queensland, Brisbane, Australia.
Katie L
KL
McMahon
University of Maryland, Baltimore, MD, USA.
Braxton
B
Mitchell
University of Texas Health Science Center San Antonio, San Antonio, TX, USA.
Rene L
RL
Olvera
Texas Biomedical Research Institute, San Antonio, TX, USA.
Charles
C
Peterson
University of Edinburgh, Edinburgh, UK.
John
J
Starr
University of Edinburgh, Edinburgh, UK.
Jessika
J
Sussmann
University of Edinburgh, Edinburgh, UK.
Joanna
J
Wardlaw
QIMR Berghofer, Brisbane, Australia.
Margie
M
Wright
VU University, Amsterdam, The Netherlands.
Dorret I
DI
Boomsma
University Medical Center Utrecht, Utrecht, The Netherlands.
Rene
R
Kahn
VU University, Amsterdam, The Netherlands.
Eco J C
EJ
de Geus
University of Texas Health Science Center San Antonio, San Antonio, TX, USA.
Douglas E
DE
Williamson
Duke University, Durham, NC, USA.
Ahmad
A
Hariri
VU University, Amsterdam, The Netherlands.
Dennis
D
van 't Ent
University of Edinburgh, Edinburgh, UK.
Mark E
ME
Bastin
University of Edinburgh, Edinburgh, UK.
Andrew
A
McIntosh
University of Edinburgh, Edinburgh, UK.
Ian J
IJ
Deary
University Medical Center Utrecht, Utrecht, The Netherlands.
Hilleke E
HE
Hulshoff Pol
Texas Biomedical Research Institute, San Antonio, TX, USA.
John
J
Blangero
Imaging Genetics Center, Institute for Neuroimaging and Informatics, Department of Neurology Keck School of Medicine, University of Southern CA, Marina del Rey, USA.
Paul M
PM
Thompson
Olin Neuropsychiatry Research Center, Institute of Living, Hartford Hospital, Hartford, USA.
David C
DC
Glahn
Anatomy & Neurobiology Department, Washington University in St. Louis, St. Louis, USA.
David C
DC
Van Essen
D000328:Adult; D016880:Anisotropy; D015331:Cohort Studies; D063132:Connectome / Q000379:methods*; D056324:Diffusion Tensor Imaging / Q000379:methods*; D005260:Female; D055614:Genetic Phenomena; D006801:Humans; D008297:Male; D009415:Nerve Net / Q000033:anatomy & histology*; D012042:Registries; D066127:White Matter / Q000033:anatomy & histology*; D055815:Young Adult