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Published in: Brain Structure and Function 1/2022

01-01-2022 | Magnetic Resonance Imaging | Original Article

Genetic and environmental influences of variation in diffusion MRI measures of white matter microstructure

Authors: Zhan Luo, Nagesh Adluru, Douglas C. Dean III, Andrew L. Alexander, H. Hill Goldsmith

Published in: Brain Structure and Function | Issue 1/2022

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Abstract

Quantitative neuroimaging studies in twin samples can investigate genetic contributions to brain structure and microstructure. Diffusion tensor imaging (DTI) studies with twin samples have shown moderate to high heritability in white matter microstructure. This study investigates the genetic and environmental contributions of another widely used diffusion MRI model not yet applied to twin studies, neurite orientation dispersion and density imaging (NODDI). The NODDI model is a multicompartment model of the diffusion-weighted MRI signal, providing estimates of neurite density (ND) and the orientation dispersion index (ODI). A cohort of monozygotic (MZ) and same-sex dizygotic (DZ) twins (N = 460 individuals) between 13 and 24 years of age were scanned with a multi-shell diffusion weighted imaging protocol. Select white matter (WM) regions of interest (ROI) were extracted. Biometric structural equation modeling estimated the relative contributions from additive genetic (A) and common (C) and unique environmental (E) factors. Genetic factors for the NODDI measures accounted for 91% and 65% of the variation of global ND and ODI, respectively, compared with 83% for FA. We observed higher heritability for ND than both FA and ODI in 25 of 30 discrete white matter regions that we examined, suggesting ND may be more sensitive to underlying genetic sources of variation. This study demonstrated that genetic factors play a key role in the development of white matter microstructure using both DTI and NODDI.
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Literature
go back to reference Bigos KL, Hariri AR, Weinberger DR (eds) (2016) Neuroimaging genetics: principles and practices. Oxford University Press, Oxford, New York Bigos KL, Hariri AR, Weinberger DR (eds) (2016) Neuroimaging genetics: principles and practices. Oxford University Press, Oxford, New York
go back to reference Colgan N, Siow B, O’Callaghan JM, Harrison IF, Wells JA, Holmes HE, Ismail O, Richardson S, Alexander DC, Collins EC, Fisher EM, Johnson R, Schwarz AJ, Ahmed Z, O’Neill MJ, Murray TK, Zhang H, Lythgoe MF (2016) Application of neurite orientation dispersion and density imaging (NODDI) to a tau pathology model of Alzheimer’s disease. Neuroimage 125:739–744. https://doi.org/10.1016/j.neuroimage.2015.10.043CrossRefPubMed Colgan N, Siow B, O’Callaghan JM, Harrison IF, Wells JA, Holmes HE, Ismail O, Richardson S, Alexander DC, Collins EC, Fisher EM, Johnson R, Schwarz AJ, Ahmed Z, O’Neill MJ, Murray TK, Zhang H, Lythgoe MF (2016) Application of neurite orientation dispersion and density imaging (NODDI) to a tau pathology model of Alzheimer’s disease. Neuroimage 125:739–744. https://​doi.​org/​10.​1016/​j.​neuroimage.​2015.​10.​043CrossRefPubMed
go back to reference Falconer DS, Mackay TFC (1996) Introduction to quantitative genetics, 4th edn. Longmans Green, Harlow, Essex, UK Falconer DS, Mackay TFC (1996) Introduction to quantitative genetics, 4th edn. Longmans Green, Harlow, Essex, UK
go back to reference Jahanshad N, Kochunov PV, Sprooten E, Mandl RC, Nichols TE, Almasy L, Blangero J, Brouwer RM, Curran JE, de Zubicaray GI, Duggirala R, Fox PT, Hong LE, Landman BA, Martin NG, McMahon KL, Medland SE, Mitchell BD, Olvera RL, Peterson CP, Starr JM, Sussmann JE, Toga AW, Wardlaw JM, Wright MJ, Hulshoff Pol HE, Bastin ME, McIntosh AM, Deary IJ, Thompson PM, Glahn DC (2013) Multi-site genetic analysis of diffusion images and voxelwise heritability analysis: a pilot project of the ENIGMA-DTI working group. Neuroimage 81:455–469. https://doi.org/10.1016/j.neuroimage.2013.04.061CrossRefPubMed Jahanshad N, Kochunov PV, Sprooten E, Mandl RC, Nichols TE, Almasy L, Blangero J, Brouwer RM, Curran JE, de Zubicaray GI, Duggirala R, Fox PT, Hong LE, Landman BA, Martin NG, McMahon KL, Medland SE, Mitchell BD, Olvera RL, Peterson CP, Starr JM, Sussmann JE, Toga AW, Wardlaw JM, Wright MJ, Hulshoff Pol HE, Bastin ME, McIntosh AM, Deary IJ, Thompson PM, Glahn DC (2013) Multi-site genetic analysis of diffusion images and voxelwise heritability analysis: a pilot project of the ENIGMA-DTI working group. Neuroimage 81:455–469. https://​doi.​org/​10.​1016/​j.​neuroimage.​2013.​04.​061CrossRefPubMed
go back to reference Kochunov P, Jahanshad N, Marcus D, Winkler A, Sprooten E, Nichols TE, Wright SN, Hong LE, Patel B, Behrens T, Jbabdi S, Andersson J, Lenglet C, Yacoub E, Moeller S, Auerbach E, Ugurbil K, Sotiropoulos SN, Brouwer RM, Landman B, Lemaitre H, den Braber A, Zwiers MP, Ritchie S, van Hulzen K, Almasy L, Curran J, deZubicaray GI, Duggirala R, Fox P, Martin NG, McMahon KL, Mitchell B, Olvera RL, Peterson C, Starr J, Sussmann J, Wardlaw J, Wright M, Boomsma DI, Kahn R, de Geus EJC, Williamson DE, Hariri A, van’t Ent D, Bastin ME, McIntosh A, Deary IJ, Hulshoff Pol HE, Blangero J, Thompson PM, Glahn DC, Van Essen DC (2015) Heritability of fractional anisotropy in human white matter: a comparison of Human Connectome Project and ENIGMA-DTI data. Neuroimage 111:300–311. https://doi.org/10.1016/j.neuroimage.2015.02.050CrossRefPubMed Kochunov P, Jahanshad N, Marcus D, Winkler A, Sprooten E, Nichols TE, Wright SN, Hong LE, Patel B, Behrens T, Jbabdi S, Andersson J, Lenglet C, Yacoub E, Moeller S, Auerbach E, Ugurbil K, Sotiropoulos SN, Brouwer RM, Landman B, Lemaitre H, den Braber A, Zwiers MP, Ritchie S, van Hulzen K, Almasy L, Curran J, deZubicaray GI, Duggirala R, Fox P, Martin NG, McMahon KL, Mitchell B, Olvera RL, Peterson C, Starr J, Sussmann J, Wardlaw J, Wright M, Boomsma DI, Kahn R, de Geus EJC, Williamson DE, Hariri A, van’t Ent D, Bastin ME, McIntosh A, Deary IJ, Hulshoff Pol HE, Blangero J, Thompson PM, Glahn DC, Van Essen DC (2015) Heritability of fractional anisotropy in human white matter: a comparison of Human Connectome Project and ENIGMA-DTI data. Neuroimage 111:300–311. https://​doi.​org/​10.​1016/​j.​neuroimage.​2015.​02.​050CrossRefPubMed
go back to reference Kochunov P, Fu M, Nugent K, Wright SN, Du X, Muellerklein F, Morrissey M, Eskandar G, Shukla DK, Jahanshad N, Thompson PM, Patel B, Postolache TT, Strauss KA, Shuldiner AR, Mitchell BD, Hong LE (2016) Heritability of complex white matter diffusion traits assessed in a population isolate. Hum Brain Mapp 37:525–535. https://doi.org/10.1002/hbm.23047CrossRefPubMed Kochunov P, Fu M, Nugent K, Wright SN, Du X, Muellerklein F, Morrissey M, Eskandar G, Shukla DK, Jahanshad N, Thompson PM, Patel B, Postolache TT, Strauss KA, Shuldiner AR, Mitchell BD, Hong LE (2016) Heritability of complex white matter diffusion traits assessed in a population isolate. Hum Brain Mapp 37:525–535. https://​doi.​org/​10.​1002/​hbm.​23047CrossRefPubMed
go back to reference Reeder SB, Pineda AR, Wen Z, Shimakawa A, Yu H, Brittain JH, Gold GE, Beaulieu CH, Pelc NJ (2005) Iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL): application with fast spin-echo imaging. Magn Reson Med 54:636–644. https://doi.org/10.1002/mrm.20624CrossRefPubMed Reeder SB, Pineda AR, Wen Z, Shimakawa A, Yu H, Brittain JH, Gold GE, Beaulieu CH, Pelc NJ (2005) Iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL): application with fast spin-echo imaging. Magn Reson Med 54:636–644. https://​doi.​org/​10.​1002/​mrm.​20624CrossRefPubMed
go back to reference Schmidt NL, Brooker RJ, Carroll IC, Gagne JR, Luo Z, Moore MN, Planalp EM, Sarkisian KL, Schmidt CK, Van Hulle CA, Lemery-Chalfant K, Goldsmith HH (2019) Longitudinal research at the interface of affective neuroscience, developmental psychopathology, health and behavioral genetics: findings from the Wisconsin twin project. Twin Res Hum Genet 22:233–239. https://doi.org/10.1017/thg.2019.55CrossRefPubMedPubMedCentral Schmidt NL, Brooker RJ, Carroll IC, Gagne JR, Luo Z, Moore MN, Planalp EM, Sarkisian KL, Schmidt CK, Van Hulle CA, Lemery-Chalfant K, Goldsmith HH (2019) Longitudinal research at the interface of affective neuroscience, developmental psychopathology, health and behavioral genetics: findings from the Wisconsin twin project. Twin Res Hum Genet 22:233–239. https://​doi.​org/​10.​1017/​thg.​2019.​55CrossRefPubMedPubMedCentral
go back to reference Vuoksimaa E, Panizzon MS, Hagler DJ, Hatton SN, Fennema-Notestine C, Rinker D, Eyler LT, Franz CE, Lyons MJ, Neale MC, Tsuang MT, Dale AM, Kremen WS (2017) Heritability of white matter microstructure in late middle age: a twin study of tract-based fractional anisotropy and absolute diffusivity indices. Hum Brain Mapp 38:2026–2036. https://doi.org/10.1002/hbm.23502CrossRefPubMed Vuoksimaa E, Panizzon MS, Hagler DJ, Hatton SN, Fennema-Notestine C, Rinker D, Eyler LT, Franz CE, Lyons MJ, Neale MC, Tsuang MT, Dale AM, Kremen WS (2017) Heritability of white matter microstructure in late middle age: a twin study of tract-based fractional anisotropy and absolute diffusivity indices. Hum Brain Mapp 38:2026–2036. https://​doi.​org/​10.​1002/​hbm.​23502CrossRefPubMed
Metadata
Title
Genetic and environmental influences of variation in diffusion MRI measures of white matter microstructure
Authors
Zhan Luo
Nagesh Adluru
Douglas C. Dean III
Andrew L. Alexander
H. Hill Goldsmith
Publication date
01-01-2022
Publisher
Springer Berlin Heidelberg
Published in
Brain Structure and Function / Issue 1/2022
Print ISSN: 1863-2653
Electronic ISSN: 1863-2661
DOI
https://doi.org/10.1007/s00429-021-02393-7

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