@article {8975,
	title = {Genetic Heterogeneity in Depressive Symptoms Following the Death of a Spouse: Polygenic Score Analysis of the U.S. Health and Retirement Study},
	journal = {American Journal of Psychiatry},
	volume = {174},
	year = {2017},
	month = {10/2017},
	pages = {963-970},
	abstract = {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 {\textquotedblleft}diathesis-stress{\textquotedblright} 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{\textquoteright}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.},
	keywords = {Bereavement, Depressive symptoms, Genetics},
	issn = {0002-953X},
	doi = {10.1176/appi.ajp.2017.16111209},
	url = {http://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2017.16111209},
	author = {Benjamin W Domingue and Hexuan Liu and Okbay, Aysu and Daniel W. Belsky}
}
