Multi-Table Differential Correlation Analysis of Neuroanatomical and Cognitive Interactions in Turner Syndrome
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ORIGINAL ARTICLE
Multi-Table Differential Correlation Analysis of Neuroanatomical and Cognitive Interactions in Turner Syndrome Christof Seiler1 · Tamar Allan L. Reiss2,5
Green2,3 · David
Hong2 · Lindsay
Chromik2 · Lynne
Huffman4 · Susan
Holmes1 ·
© Springer Science+Business Media, LLC, part of Springer Nature 2017
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
Christof Seiler and Tamar Green are joint first authors. Susan Holmes and Allan L. Reiss are joint senior authors. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12021-017-9351-z) contains supplementary material, which is available to authorized users. Christof Seiler
[email protected] 1
Department of Statistics, Stanford University, Stanford, CA, USA
2
Center for Interdisciplinary Brain Sciences Research, Stanford University School of Medicine, Stanford, CA, USA
3
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
4
Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA
5
Departments of Radiology, Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA
Introduction Turner syndrome (TS) is a genetic disorder caused by a complete or partial absence of one X-chromosome in females. TS occurs in about 1 in 2000 newborn girls (Sybert and McCauley 2004; Gravholt 2005) and has been linked to complex aberrant neuroanatomy (e.g. Hong et al. 2014) and selective impairments in cognitive function (e.g. Hong et al. 2009). Associations between neuroanatomical and cognit
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