title: Genetics of microstructure of the corpus callosum in older adults.
abstract: The current study sought to examine the relative influence of genetic and environmental factors on corpus callosum (CC) microstructure in a community sample of older adult twins. Analyses were undertaken in 284 healthy older twins (66% female; 79 MZ and 63 DZ pairs) from the Older Australian Twins Study. The average age of the sample was 69.82 (SD = 4.76) years. Brain imaging scans were collected and DTI measures were estimated for the whole CC as well as its five subregions. Parcellation of the CC was performed using Analyze. In addition, white matter lesion (WMLs) burden was estimated. Heritability and genetic correlation analyses were undertaken using the SOLAR software package. Age, sex, scanner, handedness and blood pressure were considered as covariates. Heritability (h(2)) analysis for the DTI metrics of whole CC, indicated significant h(2) for fractional anisotropy (FA) (h(2) = 0.56; p = 2.89×10(-10)), mean diffusivity (MD) (h(2) = 0.52; p = 0.30×10(-6)), radial diffusivity (RD) (h(2) = 0.49; p = 0.2×10(-6)) and axial diffusivity (AD) (h(2) = 0.37; p = 8.15×10(-5)). We also performed bivariate genetic correlation analyses between (i) whole CC DTI measures and (ii) whole CC DTI measures with total brain WML burden. Across the DTI measures for the whole CC, MD and RD shared 84% of the common genetic variance, followed by MD-AD (77%), FA-RD (52%), RD-AD (37%) and FA-MD (11%). For total WMLs, significant genetic correlations indicated that there was 19% shared common genetic variance with whole CC MD, followed by CC RD (17%), CC AD (16%) and CC FA (5%). Our findings suggest that the CC microstructure is under moderate genetic control. There was also evidence of shared genetic factors between the CC DTI measures. In contrast, there was less shared genetic variance between WMLs and the CC DTI metrics, suggesting fewer common genetic variants.
authors.affiliation: Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia.
authors.forename: Sri C
authors.initials: SC
authors.lastname: Kanchibhotla
authors.affiliation: Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Mather
authors.affiliation: Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia.
authors.forename: Anbupalam
authors.initials: A
authors.lastname: Thalamuthu
authors.affiliation: Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhuang
authors.affiliation: Neuroscience Research Australia, Sydney, Australia; School of Medical Science, University of New South Wales, Sydney, Australia.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Schofield
authors.affiliation: Neuroscience Research Australia, Sydney, Australia; School of Medical Science, University of New South Wales, Sydney, Australia.
authors.forename: John B J
authors.initials: JB
authors.lastname: Kwok
authors.affiliation: National Ageing Research Institute, Royal Melbourne Hospital, Melbourne, Australia; Academic Unit for Psychiatry of Old Age, University of Melbourne, Melbourne, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Ames
authors.affiliation: Queensland Institute Medical Research, Berghofer Medical Research Institute, Brisbane, Australia.
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Wright
authors.affiliation: Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia; Department Developmental Disability Neuropsychiatry, University of New South Wales, Sydney, Australia.
authors.forename: Julian N
authors.initials: JN
authors.lastname: Trollor
authors.affiliation: Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia; Neuropsychiatric Institute, The Prince of Wales Hospital, Sydney, Australia.
authors.forename: Wei
authors.initials: W
authors.lastname: Wen
authors.affiliation: Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia; Neuropsychiatric Institute, The Prince of Wales Hospital, Sydney, Australia.
authors.forename: Perminder S
authors.initials: PS
authors.lastname: Sachdev
mesh_terms: D000367:Age Factors; D000368:Aged; D000704:Analysis of Variance; D016880:Anisotropy; D001315:Australia; D003337:Corpus Callosum / Q000648:ultrastructure*; D005260:Female; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D009024:Morphogenesis / Q000235:genetics*; D059906:Neuroimaging