title: Genetic and environmental influences of white and gray matter signal contrast: a new phenotype for imaging genetics?
abstract: The estimation of cortical thickness is in part dependent on the degree of contrast in T1 signal intensity between white matter and gray matter along the cortical mantle. The ratio of white matter to gray matter signal (WM/GM contrast) has been found to vary as a function of age and Alzheimer's disease status, suggesting a biological component to what might otherwise be labeled as a nuisance variable. The aim of the present study was to determine if measures of WM/GM contrast are genetically influenced, as well as the degree to which this phenotype may be related to the genetic and environment determinants of cortical thickness. Participants were 514 male twins (130 monozygotic, 97 dizygotic pairs, and 60 unpaired individuals) from the Vietnam Era Twin Study of Aging. Ages ranged from 51 to 59 years. Measures of WM/GM contrast and cortical thickness were derived for 66 cortical regions of interest (ROI) using FreeSurfer-based methods. Univariate and bivariate twin analyses were used in order to estimate the heritability of WM/GM contrast, as well as the degree of shared genetic and environmental variance between WM/GM contrast and cortical thickness. WM/GM contrast was found to be significantly heritable in the majority of ROIs. The average heritability across individual ROIs was highest in the occipital lobe (.50), and lowest in the cingulate cortex (.24). Significant phenotypic correlations between WM/GM contrast and cortical thickness were observed for most of the ROIs. The majority of the phenotypic correlations were negative, ranging from ?.11 to ?.54. Of the 66 associations, only 17 significant genetic correlations were found, ranging from ?.16 to ?.34, indicating small amounts of shared genetic variance. The majority of the phenotypic correlations were accounted for by small unique environmental effects common between WM/GM contrast and cortical thickness. These findings demonstrate that like cortical thickness, WM/GM contrast is a genetically influenced brain structure phenotype. The lack of significant genetic correlations with cortical thickness suggests that this measure potentially represents a unique source of genetic variance, one that has yet to be explored by the field of imaging genetics.
authors.affiliation: Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USA. mspanizz@ucsd.edu
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Panizzon
authors.forename: Christine
authors.initials: C
authors.lastname: Fennema-Notestine
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Kubarych
authors.forename: Chi-Hua
authors.initials: CH
authors.lastname: Chen
authors.forename: Lisa T
authors.initials: LT
authors.lastname: Eyler
authors.forename: Bruce
authors.initials: B
authors.lastname: Fischl
authors.forename: Carol E
authors.initials: CE
authors.lastname: Franz
authors.forename: Michael D
authors.initials: MD
authors.lastname: Grant
authors.forename: Samar
authors.initials: S
authors.lastname: Hamza
authors.forename: Amy
authors.initials: A
authors.lastname: Jak
authors.forename: Terry L
authors.initials: TL
authors.lastname: Jernigan
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Lyons
authors.forename: Michael C
authors.initials: MC
authors.lastname: Neale
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Prom-Wormley
authors.forename: Larry
authors.initials: L
authors.lastname: Seidman
authors.forename: Ming T
authors.initials: MT
authors.lastname: Tsuang
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.forename: Hong
authors.initials: H
authors.lastname: Xian
authors.forename: Anders M
authors.initials: AM
authors.lastname: Dale
authors.forename: William S
authors.initials: WS
authors.lastname: Kremen
mesh_terms: D000375:Aging / Q000235:genetics* / Q000473:pathology*; D001921:Brain; D002540:Cerebral Cortex / Q000473:pathology*; D004777:Environment; D056726:Genetic Association Studies; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D009474:Neurons / Q000473:pathology*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D014427:Twins / Q000235:genetics* / Q000706:statistics & numerical data; D014481:United States; D014728:Veterans / Q000706:statistics & numerical data; D047829:Vietnam Conflict