The common genetic influence over processing speed and white matter microstructure: Evidence from the Old Order Amish and Human Connectome Projects.
Speed with which brain performs information processing influences overall cognition and is dependent on the white matter fibers. To understand genetic influences on processing speed and white matter FA, we assessed processing speed and diffusion imaging fractional anisotropy (FA) in related individuals from two populations. Discovery analyses were performed in 146 individuals from large Old Order Amish (OOA) families and findings were replicated in 485 twins and siblings of the Human Connectome Project (HCP). The heritability of processing speed was h(2)=43% and 49% (both p<0.005), while the heritability of whole brain FA was h(2)=87% and 88% (both p<0.001), in the OOA and HCP, respectively. Whole brain FA was significantly correlated with processing speed in the two cohorts. Quantitative genetic analysis demonstrated a significant degree to which common genes influenced joint variation in FA and brain processing speed. These estimates suggested common sets of genes influencing variation in both phenotypes, consistent with the idea that common genetic variations contributing to white matter may also support their associated cognitive behavior.
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA. Electronic address: pkochunov@mprc.umaryland.edu.
Peter
P
Kochunov
Imaging Genetics Center, Keck School of Medicine of USC, Marina del Rey, CA, USA.
Paul M
PM
Thompson
FMRIB Centre, Oxford University, Oxford, UK.
Anderson
A
Winkler
Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
Mary
M
Morrissey
Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
Mao
M
Fu
Department of Psychology, University of Texas at San Antonio, San Antonio, TX, USA.
Thomas R
TR
Coyle
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
Xiaoming
X
Du
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
Florian
F
Muellerklein
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
Anya
A
Savransky
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
Christopher
C
Gaudiot
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
Hemalatha
H
Sampath
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
George
G
Eskandar
Imaging Genetics Center, Keck School of Medicine of USC, Marina del Rey, CA, USA.
Neda
N
Jahanshad
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
Binish
B
Patel
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
Laura
L
Rowland
Department of Statistics, University of Warwick, Warwick, UK.
Thomas E
TE
Nichols
Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
Jeffrey R
JR
O'Connell
Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
Alan R
AR
Shuldiner
Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA; Geriatrics Research and Education Clinical Center, Baltimore Veterans Administration Medical Center, Baltimore, MD 21201, USA.
Braxton D
BD
Mitchell
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
L Elliot
LE
Hong
D000293:Adolescent; D000328:Adult; D000368:Aged; D061365:Amish / Q000235:genetics; D016880:Anisotropy; D001921:Brain / Q000502:physiology*; D001931:Brain Mapping; D003071:Cognition / Q000502:physiology*; D056324:Diffusion Tensor Imaging; D005260:Female; D005838:Genotype; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012042:Registries; D066127:White Matter / Q000502:physiology*; D055815:Young Adult