Two Sources of Genetic Liability to Depression: Interpreting the Relationship Between Stress Sensitivity and Depression Under a Multifactorial Polygenic Model

Abstract

Psychopathology theories, clinical observations, and research all point to multiple sources of liability to depression. This article uses a longitudinal twin-study design to characterize the contribution of two genetically-influenced sources of depression risk: the first corresponding to stress sensitivity and the second representing risk that is independent of stress sensitivity. The sample consisted of 606 pairs of same-sex adolescent twins recruited from Beijing, China. Mean (SD) age at intake (Wave1) and follow-up (Wave2) was 13.2 (2.6) and 15.1 (2.6) years, respectively. A Reaction Level index was developed to reflect individual differences in stress sensitivity. Biometric models were fit to examine the genetic influence on the variance of and covariance between stress sensitivity and depressive symptoms. Results showed that both Reaction Level and depressive symptoms were moderately heritable. The genetic correlation between depressive symptoms and Reaction Level was estimated to be .884. Genetic contributions to Reaction Level accounted for 37.5% of the total variance of depressive symptoms. Another set of genetic factors, which did not contribute to Reaction Level, accounted for 10.5% of the total variance of depressive symptoms. We interpret our results within the context of a multifactorial polygenic model, whereby depression risk is due to the combined contribution of multiple genetic and environmental factors.

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Acknowledgments

This study was funded by the Knowledge Innovation Program of the Chinese Academy of Sciences (KSCX2-EW-J-8) and the National Natural Science Foundation of China (31170993). The first author was a postdoctoral guest worker in the Department of Psychology and the Institute of Child Development at the University of Minnesota while working on this project. We thank all the personnel involved in the sample recruitment and data collection. We dedicate this article to the memory of our late and beloved colleague Dr. Xiaojia Ge for his great contribution in founding the Beijing Adolescent Twin Project.

Conflict of interest

The authors do not have any financial relationship with the organization that sponsored the research. We have full control of all primary data and we agree to allow the journal to review our data if requested.

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Correspondence to Irving I. Gottesman.

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Edited by Deborah Finkel.

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Li, X., McGue, M. & Gottesman, I.I. Two Sources of Genetic Liability to Depression: Interpreting the Relationship Between Stress Sensitivity and Depression Under a Multifactorial Polygenic Model. Behav Genet 42, 268–277 (2012). https://doi.org/10.1007/s10519-011-9506-x

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Keywords

  • China
  • Twins
  • Stress sensitivity
  • Endophenotype
  • Depressive symptoms
  • Adolescence