The common genetic influence over processing speed and white matter microstructure: Evidence from the Old Order Amish and Human Connectome Projects

• Published in: NeuroImage (Orlando, Fla.) Vol. 125; pp. 189 - 197
• Main Authors: Kochunov, Peter, Thompson, Paul M., Winkler, Anderson, Morrissey, Mary, Fu, Mao, Coyle, Thomas R., Du, Xiaoming, Muellerklein, Florian, Savransky, Anya, Gaudiot, Christopher, Sampath, Hemalatha, Eskandar, George, Jahanshad, Neda, Patel, Binish, Rowland, Laura, Nichols, Thomas E., O'Connell, Jeffrey R., Shuldiner, Alan R., Mitchell, Braxton D., Hong, L. Elliot
• Format: Journal Article Web Resource
• Language: English
• Published: United States Elsevier Inc 15.01.2016; Elsevier Limited; Elsevier
• Subjects: Adolescent; Adult; Age; Aged; Amish - genetics; Anatomie (cytologie, histologie, embryologie...) & physiologie; Anatomy (cytology, histology, embryology...) & physiology; Anisotropy; Attention deficit hyperactivity disorder; Brain - physiology; Brain Mapping; Brain research; Cognition - physiology; Diffusion Tensor Imaging; Female; Genetics & genetic processes; Genotype; Génétique & processus génétiques; Humans; Image Interpretation, Computer-Assisted; Information processing; Life sciences; Male; Medical imaging; Microstructure; Middle Aged; Neural networks; Phenotype; Registries; Sciences du vivant; Values; White Matter - physiology; Young Adult
• ISSN: 1053-8119; 1095-9572; 1095-9572
• DOI: 10.1016/j.neuroimage.2015.10.050

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 h2=43% and 49% (both p<0.005), while the heritability of whole brain FA was h2=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. •Phenotypic correlations were observed between FA and processing speed in OOA.•Genetic analysis demonstrated significant pleiotropy between two measurements.•Both findings were replicated in HCP subject.•Sets stage for bivariate genetic analyses to identify specific genes behind this relationship