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

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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.

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Notes

  1. https://github.com/ChristofSeiler/braincog

  2. https://github.com/ChristofSeiler/braincog_manuscript

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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.

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Authors and Affiliations

  1. Department of Statistics, Stanford University, Stanford, CA, USA

    Christof Seiler & Susan Holmes

  2. Center for Interdisciplinary Brain Sciences Research, Stanford University School of Medicine, Stanford, CA, USA

    Tamar Green, David Hong, Lindsay Chromik & Allan L. Reiss

  3. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Tamar Green

  4. Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA

    Lynne Huffman

  5. Departments of Radiology, Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA

    Allan L. Reiss

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  1. Christof Seiler
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Correspondence to Christof Seiler.

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Christof Seiler and Tamar Green are joint first authors. Susan Holmes and Allan L. Reiss are joint senior authors.

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Seiler, C., Green, T., Hong, D. et al. Multi-Table Differential Correlation Analysis of Neuroanatomical and Cognitive Interactions in Turner Syndrome. Neuroinform 16, 81–93 (2018). https://doi.org/10.1007/s12021-017-9351-z

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