Multi-site study of additive genetic effects on fractional anisotropy of cerebral white matter: Comparing meta and megaanalytical approaches for data pooling

Peter Kochunov, Neda Jahanshad, Emma Sprooten, Thomas E. Nichols, René C. Mandl, Laura Almasy, Tom Booth, Rachel M. Brouwer, Joanne E. Curran, Greig I. de Zubicaray, Rali Dimitrova, Ravi Duggirala, Peter T Fox, L. Elliot Hong, Bennett A. Landman, Hervé Lemaitre, Lorna M. Lopez, Nicholas G. Martin, Katie L. McMahon, Braxton D. MitchellRene L Olvera, Charles P. Peterson, John M. Starr, Jessika E. Sussmann, Arthur W. Toga, Joanna M. Wardlaw, Margaret J. Wright, Susan N. Wright, Mark E. Bastin, Andrew M. McIntosh, Dorret I. Boomsma, René S. Kahn, Anouk den Braber, Eco J C de Geus, Ian J. Deary, Hilleke E. Hulshoff Pol, Douglas E. Williamson, John Blangero, Dennis van 't Ent, Paul M. Thompson, David C. Glahn

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Combining datasets across independent studies can boost statistical power by increasing the numbers of observations and can achieve more accurate estimates of effect sizes. This is especially important for genetic studies where a large number of observations are required to obtain sufficient power to detect and replicate genetic effects. There is a need to develop and evaluate methods for joint-analytical analyses of rich datasets collected in imaging genetics studies. The ENIGMA-DTI consortium is developing and evaluating approaches for obtaining pooled estimates of heritability through meta-and mega-genetic analytical approaches, to estimate the general additive genetic contributions to the intersubject variance in fractional anisotropy (FA) measured from diffusion tensor imaging (DTI). We used the ENIGMA-DTI data harmonization protocol for uniform processing of DTI data from multiple sites. We evaluated this protocol in five family-based cohorts providing data from a total of 2248 children and adults (ages: 9-85) collected with various imaging protocols. We used the imaging genetics analysis tool, SOLAR-Eclipse, to combine twin and family data from Dutch, Australian and Mexican-American cohorts into one large "mega-family". We showed that heritability estimates may vary from one cohort to another. We used two meta-analytical (the sample-size and standard-error weighted) approaches and a mega-genetic analysis to calculate heritability estimates across-population. We performed leave-one-out analysis of the joint estimates of heritability, removing a different cohort each time to understand the estimate variability. Overall, meta- and mega-genetic analyses of heritability produced robust estimates of heritability.

Original languageEnglish (US)
Pages (from-to)136-150
Number of pages15
JournalNeuroImage
Volume95
DOIs
StatePublished - 2014

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Diffusion Tensor Imaging
Anisotropy
Meta-Analysis
Joints
Sample Size
White Matter
Population
Datasets

Keywords

  • Diffusion tensor imaging (DTI)
  • Heritability
  • Imaging genetics
  • Meta-analysis
  • Multi-site
  • Reliability

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Neurology

Cite this

Multi-site study of additive genetic effects on fractional anisotropy of cerebral white matter : Comparing meta and megaanalytical approaches for data pooling. / Kochunov, Peter; Jahanshad, Neda; Sprooten, Emma; Nichols, Thomas E.; Mandl, René C.; Almasy, Laura; Booth, Tom; Brouwer, Rachel M.; Curran, Joanne E.; de Zubicaray, Greig I.; Dimitrova, Rali; Duggirala, Ravi; Fox, Peter T; Elliot Hong, L.; Landman, Bennett A.; Lemaitre, Hervé; Lopez, Lorna M.; Martin, Nicholas G.; McMahon, Katie L.; Mitchell, Braxton D.; Olvera, Rene L; Peterson, Charles P.; Starr, John M.; Sussmann, Jessika E.; Toga, Arthur W.; Wardlaw, Joanna M.; Wright, Margaret J.; Wright, Susan N.; Bastin, Mark E.; McIntosh, Andrew M.; Boomsma, Dorret I.; Kahn, René S.; den Braber, Anouk; de Geus, Eco J C; Deary, Ian J.; Hulshoff Pol, Hilleke E.; Williamson, Douglas E.; Blangero, John; van 't Ent, Dennis; Thompson, Paul M.; Glahn, David C.

In: NeuroImage, Vol. 95, 2014, p. 136-150.

Research output: Contribution to journalArticle

Kochunov, P, Jahanshad, N, Sprooten, E, Nichols, TE, Mandl, RC, Almasy, L, Booth, T, Brouwer, RM, Curran, JE, de Zubicaray, GI, Dimitrova, R, Duggirala, R, Fox, PT, Elliot Hong, L, Landman, BA, Lemaitre, H, Lopez, LM, Martin, NG, McMahon, KL, Mitchell, BD, Olvera, RL, Peterson, CP, Starr, JM, Sussmann, JE, Toga, AW, Wardlaw, JM, Wright, MJ, Wright, SN, Bastin, ME, McIntosh, AM, Boomsma, DI, Kahn, RS, den Braber, A, de Geus, EJC, Deary, IJ, Hulshoff Pol, HE, Williamson, DE, Blangero, J, van 't Ent, D, Thompson, PM & Glahn, DC 2014, 'Multi-site study of additive genetic effects on fractional anisotropy of cerebral white matter: Comparing meta and megaanalytical approaches for data pooling', NeuroImage, vol. 95, pp. 136-150. https://doi.org/10.1016/j.neuroimage.2014.03.033
Kochunov, Peter ; Jahanshad, Neda ; Sprooten, Emma ; Nichols, Thomas E. ; Mandl, René C. ; Almasy, Laura ; Booth, Tom ; Brouwer, Rachel M. ; Curran, Joanne E. ; de Zubicaray, Greig I. ; Dimitrova, Rali ; Duggirala, Ravi ; Fox, Peter T ; Elliot Hong, L. ; Landman, Bennett A. ; Lemaitre, Hervé ; Lopez, Lorna M. ; Martin, Nicholas G. ; McMahon, Katie L. ; Mitchell, Braxton D. ; Olvera, Rene L ; Peterson, Charles P. ; Starr, John M. ; Sussmann, Jessika E. ; Toga, Arthur W. ; Wardlaw, Joanna M. ; Wright, Margaret J. ; Wright, Susan N. ; Bastin, Mark E. ; McIntosh, Andrew M. ; Boomsma, Dorret I. ; Kahn, René S. ; den Braber, Anouk ; de Geus, Eco J C ; Deary, Ian J. ; Hulshoff Pol, Hilleke E. ; Williamson, Douglas E. ; Blangero, John ; van 't Ent, Dennis ; Thompson, Paul M. ; Glahn, David C. / Multi-site study of additive genetic effects on fractional anisotropy of cerebral white matter : Comparing meta and megaanalytical approaches for data pooling. In: NeuroImage. 2014 ; Vol. 95. pp. 136-150.
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T2 - Comparing meta and megaanalytical approaches for data pooling

AU - Kochunov, Peter

AU - Jahanshad, Neda

AU - Sprooten, Emma

AU - Nichols, Thomas E.

AU - Mandl, René C.

AU - Almasy, Laura

AU - Booth, Tom

AU - Brouwer, Rachel M.

AU - Curran, Joanne E.

AU - de Zubicaray, Greig I.

AU - Dimitrova, Rali

AU - Duggirala, Ravi

AU - Fox, Peter T

AU - Elliot Hong, L.

AU - Landman, Bennett A.

AU - Lemaitre, Hervé

AU - Lopez, Lorna M.

AU - Martin, Nicholas G.

AU - McMahon, Katie L.

AU - Mitchell, Braxton D.

AU - Olvera, Rene L

AU - Peterson, Charles P.

AU - Starr, John M.

AU - Sussmann, Jessika E.

AU - Toga, Arthur W.

AU - Wardlaw, Joanna M.

AU - Wright, Margaret J.

AU - Wright, Susan N.

AU - Bastin, Mark E.

AU - McIntosh, Andrew M.

AU - Boomsma, Dorret I.

AU - Kahn, René S.

AU - den Braber, Anouk

AU - de Geus, Eco J C

AU - Deary, Ian J.

AU - Hulshoff Pol, Hilleke E.

AU - Williamson, Douglas E.

AU - Blangero, John

AU - van 't Ent, Dennis

AU - Thompson, Paul M.

AU - Glahn, David C.

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KW - Heritability

KW - Imaging genetics

KW - Meta-analysis

KW - Multi-site

KW - Reliability

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