Polygenic Liability to Depression Is Associated With Multiple Medical Conditions in the Electronic Health Record: Phenome-wide Association Study of 46,782 Individuals.
Depression
Health span
Medical condition
Mental disorder
PheWAS
Polygenic risk score
Journal
Biological psychiatry
ISSN: 1873-2402
Titre abrégé: Biol Psychiatry
Pays: United States
ID NLM: 0213264
Informations de publication
Date de publication:
15 12 2022
15 12 2022
Historique:
received:
17
10
2021
revised:
01
04
2022
accepted:
02
06
2022
pubmed:
15
8
2022
medline:
22
11
2022
entrez:
14
8
2022
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 35965108
pii: S0006-3223(22)01319-1
doi: 10.1016/j.biopsych.2022.06.004
pmc: PMC10712651
mid: NIHMS1852096
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
923-931Subventions
Organisme : NICHD NIH HHS
ID : P2C HD065563
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH101459
Pays : United States
Organisme : NICHD NIH HHS
ID : R24 HD065563
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2022 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
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