Genetic Heterogeneity in Depressive Symptoms Following the Death of a Spouse: Polygenic Score Analysis of the U.S. Health and Retirement Study.


Journal Article

OBJECTIVE:Experience of stressful life events is associated with risk of depression. Yet many exposed individuals do not become depressed. A controversial hypothesis is that genetic factors influence vulnerability to depression following stress. This hypothesis is often tested with a "diathesis-stress" model, in which genes confer excess vulnerability. The authors tested an alternative formulation of this model: genes may buffer against depressogenic effects of life stress. METHOD:The hypothesized genetic buffer was measured using a polygenic score derived from a published genome-wide association study of subjective well-being. The authors tested whether married older adults who had higher polygenic scores were less vulnerable to depressive symptoms following the death of their spouse compared with age-matched peers who had also lost their spouse and who had lower polygenic scores. Data were analyzed from 8,588 non-Hispanic white adults in the Health and Retirement Study (HRS), a population-representative longitudinal study of older adults in the United States. RESULTS:HRS adults with higher well-being polygenic scores experienced fewer depressive symptoms during follow-up. Those who survived the death of their spouses (N=1,647) experienced a sharp increase in depressive symptoms following the death and returned toward baseline over the following 2 years. Having a higher well-being polygenic score buffered against increased depressive symptoms following a spouse's death. CONCLUSIONS:The effects were small, and the clinical relevance is uncertain, although polygenic score analyses may provide clues to behavioral pathways that can serve as therapeutic targets. Future studies of gene-environment interplay in depression may benefit from focus on genetics discovered for putative protective factors.

Full Text

Cited Authors

  • Domingue, BW; Liu, H; Okbay, A; Belsky, DW

Published Date

  • October 2017

Published In

Volume / Issue

  • 174 / 10

Start / End Page

  • 963 - 970

PubMed ID

  • 28335623

Pubmed Central ID

  • 28335623

Electronic International Standard Serial Number (EISSN)

  • 1535-7228

International Standard Serial Number (ISSN)

  • 0002-953X

Digital Object Identifier (DOI)

  • 10.1176/appi.ajp.2017.16111209


  • eng