Abstract
Background
Major depressive disorder (MDD) is a leading cause of disease-associated disability,
with much of the increased burden due to psychiatric and medical comorbidity. This
comorbidity partly reflects common genetic influences across conditions. Integrating
molecular-genetic tools with health records enables tests of association with the
broad range of physiological and clinical phenotypes. However, standard phenome-wide
association studies analyze associations with individual genetic variants. For polygenic
traits such as MDD, aggregate measures of genetic risk may yield greater insight into
associations across the clinical phenome.
Methods
We tested for associations between a genome-wide polygenic risk score for MDD and
medical and psychiatric traits in a phenome-wide association study of 46,782 unrelated,
European-ancestry participants from the Michigan Genomics Initiative.
Results
The MDD polygenic risk score was associated with 211 traits from 15 medical and psychiatric
disease categories at the phenome-wide significance threshold. After excluding patients
with depression, continued associations were observed with respiratory, digestive,
neurological, and genitourinary conditions; neoplasms; and mental disorders. Associations
with tobacco use disorder, respiratory conditions, and genitourinary conditions persisted
after accounting for genetic overlap between depression and other psychiatric traits.
Temporal analyses of time-at-first-diagnosis indicated that depression disproportionately
preceded chronic pain and substance-related disorders, while asthma disproportionately
preceded depression.
Conclusions
The present results can inform the biological links between depression and both mental
and systemic diseases. Although MDD polygenic risk scores cannot currently forecast
health outcomes with precision at the individual level, as molecular-genetic discoveries
for depression increase, these tools may augment risk prediction for medical and psychiatric
conditions.
Keywords
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Article info
Publication history
Published online: June 10, 2022
Accepted:
June 2,
2022
Received in revised form:
April 1,
2022
Received:
October 17,
2021
Identification
Copyright
© 2022 Society of Biological Psychiatry.
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- Depression Genetics as a Window Into Physical and Mental HealthBiological PsychiatryVol. 92Issue 12
- PreviewPreventing depression and its concomitant health issues is critical to promote healthy aging and extend the lifespan. It is well known that depression and poor health are intertwined (1), but why they are intertwined remains an area of active inquiry. The idea that depression may share underlying biology—including common genetic mechanisms—with other health conditions is appealing, as knowledge of such mechanisms could inform treatments to ameliorate both. To that end, year upon year we are learning more about the complex genetic architecture of major depression (2), which provides us in theory with increasingly powerful genome-wide tools to study the relationship between depression and health.
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