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Neuroinformatics

, Volume 16, Issue 1, pp 81–93 | Cite as

Multi-Table Differential Correlation Analysis of Neuroanatomical and Cognitive Interactions in Turner Syndrome

  • Christof Seiler
  • Tamar Green
  • David Hong
  • Lindsay Chromik
  • Lynne Huffman
  • Susan Holmes
  • Allan L. Reiss
Original Article

Abstract

Girls and women with Turner syndrome (TS) have a completely or partially missing X chromosome. Extensive studies on the impact of TS on neuroanatomy and cognition have been conducted. The integration of neuroanatomical and cognitive information into one consistent analysis through multi-table methods is difficult and most standard tests are underpowered. We propose a new two-sample testing procedure that compares associations between two tables in two groups. The procedure combines multi-table methods with permutation tests. In particular, we construct cluster size test statistics that incorporate spatial dependencies. We apply our new procedure to a newly collected dataset comprising of structural brain scans and cognitive test scores from girls with TS and healthy control participants (age and sex matched). We measure neuroanatomy with Tensor-Based Morphometry (TBM) and cognitive function with Wechsler IQ and NEuroPSYchological tests (NEPSY-II). We compare our multi-table testing procedure to a single-table analysis. Our new procedure reports differential correlations between two voxel clusters and a wide range of cognitive tests whereas the single-table analysis reports no differences. Our findings are consistent with the hypothesis that girls with TS have a different brain-cognition association structure than healthy controls.

Keywords

Permutation tests Multi-table analysis Sparse canonical correlation analysis Turner syndrome Tensor-based morphometry Cognitive abilities 

Notes

Acknowledgments

The Turner Syndrome Society and the Turner Syndrome Foundation made this work possible. The authors would like to sincerely thank all of the families who kindly volunteered to participate.

Christof Seiler was supported by two postdoctoral fellowships from the Swiss National Science Foundation (146281 and 158500) and a travel grant from the France-Stanford Center for Interdisciplinary Studies. Tamar Green was supported by a grant from the Gazit-Globe Post-Doctoral Fellowship Award. Allan L. Reiss is supported by grants from the NICHD (HD049653), NIMH (MH099630), and the Sharon Levine Foundation. Dr. Reiss is an unpaid medical advisor for the Turner Syndrome Society and Turner Syndrome Foundation. The funding sources mentioned above had no role in the study design; in the collection, analysis and interpretation of the data. Susan Holmes is supported by NICHD (HD049653).

We would like to thank two anonymous reviewers for their helpful input that greatly contributed to improved clarity and quality of this manuscript.

Supplementary material

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2017

Authors and Affiliations

  • Christof Seiler
    • 1
  • Tamar Green
    • 2
    • 3
  • David Hong
    • 2
  • Lindsay Chromik
    • 2
  • Lynne Huffman
    • 4
  • Susan Holmes
    • 1
  • Allan L. Reiss
    • 2
    • 5
  1. 1.Department of StatisticsStanford UniversityStanfordUSA
  2. 2.Center for Interdisciplinary Brain Sciences ResearchStanford University School of MedicineStanfordUSA
  3. 3.Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael
  4. 4.Department of PediatricsStanford University School of MedicineStanfordUSA
  5. 5.Departments of Radiology, Psychiatry and Behavioral SciencesStanford University School of MedicineStanfordUSA

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