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Polygenic risk for severe psychopathology among Europeans is associated with major depressive disorder in Han Chinese women

Published online by Cambridge University Press:  03 October 2017

A. C. Edwards ,
A. R. Docherty ,
A. Moscati ,
T. B. Bigdeli ,
R. E. Peterson ,
B. T. Webb ,
S.-A. Bacanu ,
J. M. Hettema ,
J. Flint  and
K. S. Kendler
A. C. Edwards*
Affiliation:
Virginia Institute of Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA
A. R. Docherty
Affiliation:
Virginia Institute of Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA Department of Psychiatry, University Neuropsychiatric Institute, University of Utah School of Medicine, Salt Lake City, UT, USA
A. Moscati
Affiliation:
Virginia Institute of Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA
T. B. Bigdeli
Affiliation:
Virginia Institute of Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA
R. E. Peterson
Affiliation:
Virginia Institute of Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA
B. T. Webb
Affiliation:
Virginia Institute of Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA
S.-A. Bacanu
Affiliation:
Virginia Institute of Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA
J. M. Hettema
Affiliation:
Virginia Institute of Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA
J. Flint
Affiliation:
Department of Psychiatry and Biobehavioral Sciences, UCLA; David Geffen School of Medicine, Center for Neurobehavioral Genetics, UCLA; and Semel Institute for Neuroscience and Human Behavior at UCLA; Los Angeles, CA, USA
K. S. Kendler
Affiliation:
Virginia Institute of Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA
*
*Address for correspondence: A. C. Edwards, Ph.D., Virginia Institute of Psychiatric and Behavioral Genetics, Virginia Commonwealth University, PO Box 980126, Richmond, VA 23298-0126, USA. (Email: alexis.edwards@vcuhealth.org)
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Abstract

Background

Previous studies have demonstrated that several major psychiatric disorders are influenced by shared genetic factors. This shared liability may influence clinical features of a given disorder (e.g. severity, age at onset). However, findings have largely been limited to European samples; little is known about the consistency of shared genetic liability across ethnicities.

Method

The relationship between polygenic risk for several major psychiatric diagnoses and major depressive disorder (MDD) was examined in a sample of unrelated Han Chinese women. Polygenic risk scores (PRSs) were generated using European discovery samples and tested in the China, Oxford, and VCU Experimental Research on Genetic Epidemiology [CONVERGE (maximum N = 10 502)], a sample ascertained for recurrent MDD. Genetic correlations between discovery phenotypes and MDD were also assessed. In addition, within-case characteristics were examined.

Results

European-based polygenic risk for several major psychiatric disorder phenotypes was significantly associated with the MDD case status in CONVERGE. Risk for clinically significant indicators (neuroticism and subjective well-being) was also associated with case–control status. The variance accounted for by PRS for both psychopathology and for well-being was similar to estimates reported for within-ethnicity comparisons in European samples. However, European-based PRS were largely unassociated with CONVERGE family history, clinical characteristics, or comorbidity.

Conclusions

The shared genetic liability across severe forms of psychopathology is largely consistent across European and Han Chinese ethnicities, with little attenuation of genetic signal relative to within-ethnicity analyses. The overall absence of associations between PRS for other disorders and within-MDD variation suggests that clinical characteristics of MDD may arise due to contributions from ethnicity-specific factors and/or pathoplasticity.

Keywords

Major depressionpolygenic riskpsychopathologytrans-ethnic
Type
Original Articles
Information
Psychological Medicine , Volume 48 , Issue 5 , April 2018 , pp. 777 - 789
Copyright
Copyright © Cambridge University Press 2017 

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Footnotes

†

These authors contributed equally to this work.

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