title: Heritability of complex white matter diffusion traits assessed in a population isolate.
abstract: BACKGROUND
  Diffusion weighted imaging (DWI) methods can noninvasively ascertain cerebral microstructure by examining pattern and directions of water diffusion in the brain. We calculated heritability for DWI parameters in cerebral white (WM) and gray matter (GM) to study the genetic contribution to the diffusion signals across tissue boundaries.
  
  
  METHODS
  Using Old Order Amish (OOA) population isolate with large family pedigrees and high environmental homogeneity, we compared the heritability of measures derived from three representative DWI methods targeting the corpus callosum WM and cingulate gyrus GM: diffusion tensor imaging (DTI), the permeability-diffusivity (PD) model, and the neurite orientation dispersion and density imaging (NODDI) model. These successively more complex models represent the diffusion signal modeling using one, two, and three diffusion compartments, respectively.
  
  
  RESULTS
  We replicated the high heritability of the DTI-based fractional anisotropy (h(2)  = 0.67) and radial diffusivity (h(2)  = 0.72) in WM. High heritability in both WM and GM tissues were observed for the permeability-diffusivity index from the PD model (h(2)  = 0.64 and 0.84), and the neurite density from the NODDI model (h(2)  = 0.70 and 0.55). The orientation dispersion index from the NODDI model was only significantly heritable in GM (h(2)  = 0.68).
  
  
  CONCLUSIONS
  DWI measures from multicompartmental models were significantly heritable in WM and GM. DWI can offer valuable phenotypes for genetic research; and genes thus identified may reveal mechanisms contributing to mental and neurological disorders in which diffusion imaging anomalies are consistently found. Hum Brain Mapp 37:525-535, 2016. © 2015 Wiley Periodicals, Inc.
authors.affiliation: Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Peter
authors.initials: P
authors.lastname: Kochunov
authors.affiliation: Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Mao
authors.initials: M
authors.lastname: Fu
authors.affiliation: Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Katie
authors.initials: K
authors.lastname: Nugent
authors.affiliation: Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Susan N
authors.initials: SN
authors.lastname: Wright
authors.affiliation: Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Du
authors.affiliation: Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Florian
authors.initials: F
authors.lastname: Muellerklein
authors.affiliation: Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Mary
authors.initials: M
authors.lastname: Morrissey
authors.affiliation: Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: George
authors.initials: G
authors.lastname: Eskandar
authors.affiliation: Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Dinesh K
authors.initials: DK
authors.lastname: Shukla
authors.affiliation: Keck School of Medicine of USC, Imaging Genetics Center, Marina Del Rey, California.
authors.forename: Neda
authors.initials: N
authors.lastname: Jahanshad
authors.affiliation: Keck School of Medicine of USC, Imaging Genetics Center, Marina Del Rey, California.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Thompson
authors.affiliation: Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Binish
authors.initials: B
authors.lastname: Patel
authors.affiliation: Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Teodor T
authors.initials: TT
authors.lastname: Postolache
authors.affiliation: Clinic for Special Children, Strasburg, Pennsylvania.
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Strauss
authors.affiliation: Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Alan R
authors.initials: AR
authors.lastname: Shuldiner
authors.affiliation: Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland.|Veterans Affairs Maryland Health Care System, Geriatric Research and Education Clinical Center, Baltimore, Maryland.
authors.forename: Braxton D
authors.initials: BD
authors.lastname: Mitchell
authors.affiliation: Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: L Elliot
authors.initials: LE
authors.lastname: Hong
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061365:Amish; D003337:Corpus Callosum / Q000033:anatomy & histology*; D056324:Diffusion Tensor Imaging / Q000379:methods; D005260:Female; D066128:Gray Matter / Q000033:anatomy & histology; D006179:Gyrus Cinguli / Q000033:anatomy & histology; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008297:Male; D008875:Middle Aged; D008959:Models, Neurological; D010641:Phenotype; D019655:Quantitative Trait, Heritable; D066127:White Matter / Q000033:anatomy & histology*; D055815:Young Adult
keywords: DTI; DWI; genetics; heritability; imaging