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Heritable anisotropy associated with cognitive impairments among patients with schizophrenia and their non-psychotic relatives in multiplex families

Published online by Cambridge University Press:  03 September 2020

K. M. Prasad Open the ORCID record for K. M. Prasad [Opens in a new window] ,
J. Gertler ,
S. Tollefson ,
J. A. Wood ,
D. Roalf ,
R. C. Gur ,
R. E. Gur ,
L. Almasy ,
M. F. Pogue-Geile  and
V. L. Nimgaonkar
K. M. Prasad*
Affiliation:
Departments of Psychiatry and Bioengineering, University of Pittsburgh, VA Pittsburgh Healthcare System, Pittsburgh, PA, USA
J. Gertler
Affiliation:
Departments of Psychiatry and Bioengineering, University of Pittsburgh, VA Pittsburgh Healthcare System, Pittsburgh, PA, USA
S. Tollefson
Affiliation:
Departments of Psychiatry and Bioengineering, University of Pittsburgh, VA Pittsburgh Healthcare System, Pittsburgh, PA, USA
J. A. Wood
Affiliation:
Departments of Psychiatry and Bioengineering, University of Pittsburgh, VA Pittsburgh Healthcare System, Pittsburgh, PA, USA
D. Roalf
Affiliation:
Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA
R. C. Gur
Affiliation:
Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA
R. E. Gur
Affiliation:
Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA
L. Almasy
Affiliation:
Department of Genetics, University of Pennsylvania, Philadelphia, PA, USA
M. F. Pogue-Geile
Affiliation:
Department of Psychology, University of Pittsburgh, Pittsburgh, PA, USA
V. L. Nimgaonkar
Affiliation:
Departments of Psychiatry and Bioengineering, University of Pittsburgh, VA Pittsburgh Healthcare System, Pittsburgh, PA, USA Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, PA, USA VA Pittsburgh Healthcare System, Pittsburgh, PA, USA
*
Author for correspondence: K. M. Prasad, E-mail: PrasadKM@upmc.edu
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Abstract

Background

To test the functional implications of impaired white matter (WM) connectivity among patients with schizophrenia and their relatives, we examined the heritability of fractional anisotropy (FA) measured on diffusion tensor imaging data acquired in Pittsburgh and Philadelphia, and its association with cognitive performance in a unique sample of 175 multigenerational non-psychotic relatives of 23 multiplex schizophrenia families and 240 unrelated controls (total = 438).

Methods

We examined polygenic inheritance (h2r) of FA in 24 WM tracts bilaterally, and also pleiotropy to test whether heritability of FA in multiple WM tracts is secondary to genetic correlation among tracts using the Sequential Oligogenic Linkage Analysis Routines. Partial correlation tests examined the correlation of FA with performance on eight cognitive domains on the Penn Computerized Neurocognitive Battery, controlling for age, sex, site and mother's education, followed by multiple comparison corrections.

Results

Significant total additive genetic heritability of FA was observed in all three-categories of WM tracts (association, commissural and projection fibers), in total 33/48 tracts. There were significant genetic correlations in 40% of tracts. Diagnostic group main effects were observed only in tracts with significantly heritable FA. Correlation of FA with neurocognitive impairments was observed mainly in heritable tracts.

Conclusions:

Our data show significant heritability of all three-types of tracts among relatives of schizophrenia. Significant heritability of FA of multiple tracts was not entirely due to genetic correlations among the tracts. Diagnostic group main effect and correlation with neurocognitive performance were mainly restricted to tracts with heritable FA suggesting shared genetic effects on these traits.

Keywords

Brain connectivitydiffusion tensor imagingfamilial riskheritabilityschizophrenianeuroimagingwhite matter fibers
Type
Original Article
Information
Psychological Medicine , Volume 52 , Issue 5 , April 2022 , pp. 989 - 1000
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Copyright
Copyright © The Author(s), 2020. Published by Cambridge University Press

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Footnotes

*

These authors equally contributed to this work

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