title: Heritability of white matter microstructure in late middle age: A twin study of tract-based fractional anisotropy and absolute diffusivity indices.
abstract: There is evidence that differences among individuals in white matter microstructure, as measured with diffusion tensor imaging (DTI), are under genetic control. However, little is known about the relative contribution of genetic and environmental effects on different diffusivity indices among late middle-aged adults. Here, we examined the magnitude of genetic influences for fractional anisotropy (FA), and mean (MD), axial (AD), and radial (RD) diffusivities in male twins aged 56-66 years old. Using an atlas-based registration approach to delineate individual white matter tracts, we investigated mean DTI-based indices within the corpus callosum, 12 bilateral tracts and all these regions of interest combined. All four diffusivity indices had high heritability at the global level (72%-80%). The magnitude of genetic effects in individual tracts varied from 0% to 82% for FA, 0% to 81% for MD, 8% to 77% for AD, and 0% to 80% for RD with most of the tracts showing significant heritability estimates. Despite the narrow age range of this community-based sample, age was correlated with all four diffusivity indices at the global level. In sum, all diffusion indices proved to have substantial heritability for most of the tracts and the heritability estimates were similar in magnitude for different diffusivity measures. Future studies could aim to discover the particular set of genes that underlie the significant heritability of white matter microstructure. Hum Brain Mapp 38:2026-2036, 2017. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Department of Psychiatry, University of California, San Diego, La Jolla, California.|Center for Behavior Genetics of Aging University of California, San Diego, La Jolla, California.|Institute for Molecular Medicine Finland and Department of Public Health, University of Helsinki, Helsinki, Finland.
authors.forename: Eero
authors.identifier: 0000-0002-6534-3667
authors.initials: E
authors.lastname: Vuoksimaa
authors.affiliation: Department of Psychiatry, University of California, San Diego, La Jolla, California.|Center for Behavior Genetics of Aging University of California, San Diego, La Jolla, California.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Panizzon
authors.affiliation: Department of Radiology, University of California, San Diego, La Jolla, California.
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Hagler
authors.affiliation: Department of Psychiatry, University of California, San Diego, La Jolla, California.|Center for Behavior Genetics of Aging University of California, San Diego, La Jolla, California.
authors.forename: Sean N
authors.identifier: 0000-0002-9149-8726
authors.initials: SN
authors.lastname: Hatton
authors.affiliation: Department of Psychiatry, University of California, San Diego, La Jolla, California.|Department of Radiology, University of California, San Diego, La Jolla, California.
authors.forename: Christine
authors.initials: C
authors.lastname: Fennema-Notestine
authors.affiliation: Department of Psychiatry, University of California, San Diego, La Jolla, California.|Department of Radiology, University of California, San Diego, La Jolla, California.|Imaging Genetics Center, Institute for Neuroimaging and Informatics, University of Southern California, Los Angeles, California.
authors.forename: Daniel
authors.initials: D
authors.lastname: Rinker
authors.affiliation: Department of Psychiatry, University of California, San Diego, La Jolla, California.|VA San Diego Healthcare System, Mental Illness Research Education and Clinical Center, San Diego, California.
authors.forename: Lisa T
authors.initials: LT
authors.lastname: Eyler
authors.affiliation: Department of Psychiatry, University of California, San Diego, La Jolla, California.|Center for Behavior Genetics of Aging University of California, San Diego, La Jolla, California.
authors.forename: Carol E
authors.initials: CE
authors.lastname: Franz
authors.affiliation: Department of Psychology and Brain Sciences, Boston University, Boston, Massachusetts.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Lyons
authors.affiliation: Virginia Commonwealth University School of Medicine, Virginia Institute for Psychiatric and Behavioral Genetics, Richmond, Virginia.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Neale
authors.affiliation: Department of Psychiatry, University of California, San Diego, La Jolla, California.|Center for Behavior Genomics, University of California, San Diego, La Jolla, California.|Institute for Genomic Medicine, University of California, San Diego, La Jolla, California.
authors.forename: Ming T
authors.initials: MT
authors.lastname: Tsuang
authors.affiliation: Department of Radiology, University of California, San Diego, La Jolla, California.|Department of Neurosciences, University of California, San Diego, La Jolla, California.
authors.forename: Anders M
authors.initials: AM
authors.lastname: Dale
authors.affiliation: Department of Psychiatry, University of California, San Diego, La Jolla, California.|Center for Behavior Genetics of Aging University of California, San Diego, La Jolla, California.|VA San Diego Healthcare System, Center of Excellence for Stress and Mental Health, La Jolla, California.
authors.forename: William S
authors.initials: WS
authors.lastname: Kremen
mesh_terms: D000368:Aged; D016880:Anisotropy; D003337:Corpus Callosum / Q000033:anatomy & histology* / Q000000981:diagnostic imaging; D056324:Diffusion Tensor Imaging; D059647:Gene-Environment Interaction; D006801:Humans; D007091:Image Processing, Computer-Assisted; D040582:Inheritance Patterns; D008297:Male; D008875:Middle Aged; D012111:Residence Characteristics; D012189:Retrospective Studies; D014429:Twins, Dizygotic / Q000235:genetics*; D014430:Twins, Monozygotic / Q000235:genetics*; D066127:White Matter / Q000033:anatomy & histology* / Q000000981:diagnostic imaging
keywords: absolute diffusivity; diffusion tensor imaging; fractional anisotropy; genetic effects; twins