title: Genetic and environmental influences on mean diffusivity and volume in subcortical brain regions.
abstract: Increased mean diffusivity (MD) is hypothesized to reflect tissue degeneration and may provide subtle indicators of neuropathology as well as age-related brain changes in the absence of volumetric differences. Our aim was to determine the degree to which genetic and environmental variation in subcortical MD is distinct from variation in subcortical volume. Data were derived from a sample of 387 male twins (83 MZ twin pairs, 55 DZ twin pairs, and 111 incomplete twin pairs) who were MRI scanned as part of the Vietnam Era Twin Study of Aging. Quantitative estimates of MD and volume for 7 subcortical regions were obtained: thalamus, caudate nucleus, putamen, pallidum, hippocampus, amygdala, and nucleus accumbens. After adjusting for covariates, bivariate twin models were fitted to estimate the size and significance of phenotypic, genotypic, and environmental correlations between MD and volume at each subcortical region. With the exception of the amygdala, familial aggregation in MD was entirely explained by additive genetic factors across all subcortical regions with estimates ranging from 46 to 84%. Based on bivariate twin modeling, variation in subcortical MD appears to be both genetically and environmentally unrelated to individual differences in subcortical volume. Therefore, subcortical MD may be an alternative biomarker of brain morphology for complex traits worthy of future investigation. Hum Brain Mapp 38:2589-2598, 2017. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Virginia Institute for Psychiatric and Behavior Genetics, Virginia Commonwealth University, Virginia.
authors.forename: Nathan A
authors.identifier: 0000-0001-8655-2823
authors.initials: NA
authors.lastname: Gillespie
authors.affiliation: Virginia Institute for Psychiatric and Behavior Genetics, Virginia Commonwealth University, Virginia.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Neale
authors.affiliation: Department of Radiology, University of California, San Diego, California.
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Hagler
authors.affiliation: Desert-Pacific Mental Illness Research, Education, and Clinical Center, VA San Diego Healthcare System, California.|Department of Psychiatry, University of California, San Diego, California.
authors.forename: Lisa T
authors.initials: LT
authors.lastname: Eyler
authors.affiliation: Department of Radiology, University of California, San Diego, California.|Department of Psychiatry, University of California, San Diego, California.
authors.forename: Christine
authors.initials: C
authors.lastname: Fennema-Notestine
authors.affiliation: Department of Psychiatry, University of California, San Diego, California.
authors.forename: Carol E
authors.initials: CE
authors.lastname: Franz
authors.affiliation: Department of Psychological and Brain Sciences, Boston University, Boston, Massachusetts.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Lyons
authors.affiliation: Department of Radiology, University of California, San Diego, California.
authors.forename: Linda K
authors.initials: LK
authors.lastname: McEvoy
authors.affiliation: Department of Radiology, University of California, San Diego, California.|Department of Psychiatry, University of California, San Diego, California.
authors.forename: Anders M
authors.initials: AM
authors.lastname: Dale
authors.affiliation: Department of Psychiatry, University of California, San Diego, California.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Panizzon
authors.affiliation: Department of Psychiatry, University of California, San Diego, California.|Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System, California.
authors.forename: William S
authors.initials: WS
authors.lastname: Kremen
mesh_terms: D001921:Brain / Q000000981:diagnostic imaging*; D038524:Diffusion Magnetic Resonance Imaging; D059647:Gene-Environment Interaction; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D008959:Models, Neurological; D010641:Phenotype; D012189:Retrospective Studies; D014429:Twins, Dizygotic; D014430:Twins, Monozygotic
keywords: DTI; classical twin design; environmental; genes; genetic epidemiology; mean diffusivity; subcortical; volume