The actions and interactions of family genetic risk scores for alcohol use disorder and major depression on the risk for these two disorders
(2022) In American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics 189(5). p.128-138- Abstract
We know little about how genetic risk factors for two disorders jointly act and interact in predisposing to illness. Therefore, in the Swedish population, born 1970–1990 (n = 2,116,082) and followed through 2015, we examine, using additive Cox models, the impact of the family genetic risk scores (FGRS) for alcohol use disorder (AUD) and major depression (MD), their interaction with each other and with the relevant comorbid disorder on risk for AUD and MD. FGRS scores are constructed using rates of illness in first-fourth degree relatives. FGRS for AUD and MD interacted in predicting of both disorders and one FRGS (e.g., for AUD) interacted with the phenotype of MD to predict that disorder (e.g., AUD). These FGRS interactions were not... (More)
We know little about how genetic risk factors for two disorders jointly act and interact in predisposing to illness. Therefore, in the Swedish population, born 1970–1990 (n = 2,116,082) and followed through 2015, we examine, using additive Cox models, the impact of the family genetic risk scores (FGRS) for alcohol use disorder (AUD) and major depression (MD), their interaction with each other and with the relevant comorbid disorder on risk for AUD and MD. FGRS scores are constructed using rates of illness in first-fourth degree relatives. FGRS for AUD and MD interacted in predicting of both disorders and one FRGS (e.g., for AUD) interacted with the phenotype of MD to predict that disorder (e.g., AUD). These FGRS interactions were not substantially attenuated by adding interactions with the disorders. These results replicated across sexes. In predicting risk for a given disorder, we rarely consider genetic liabilities for other disorders. But such effects were here significant and interactive. Furthermore, the primary disorder genetic risk interacts with comorbid disorders. The pathways to risk for disorders from their and other disorders' genetic liability may be more complex than commonly considered.
(Less)
- author
- Kendler, Kenneth S. ; Lönn, Sara L. LU ; Sundquist, Jan LU and Sundquist, Kristina LU
- organization
- publishing date
- 2022-07
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- alcohol use disorder, family genetic risk score, interactions, major depression
- in
- American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
- volume
- 189
- issue
- 5
- pages
- 11 pages
- publisher
- International Society of Psychiatric Genetics
- external identifiers
-
- scopus:85133185579
- pmid:35779072
- ISSN
- 1552-4841
- DOI
- 10.1002/ajmg.b.32909
- language
- English
- LU publication?
- yes
- additional info
- Funding Information: This project was supported by grant R01AA023534 from the National Institutes of Health, NIAAA, grants from the Swedish Research Council, as well as Avtal om Läkarutbildning och Forskning (ALF) funding from Region Skåne.
- id
- 8652215f-1fa4-4713-b221-ba8150861095
- date added to LUP
- 2022-09-13 14:40:25
- date last changed
- 2024-06-13 19:22:25
@article{8652215f-1fa4-4713-b221-ba8150861095,
abstract = {{<p>We know little about how genetic risk factors for two disorders jointly act and interact in predisposing to illness. Therefore, in the Swedish population, born 1970–1990 (n = 2,116,082) and followed through 2015, we examine, using additive Cox models, the impact of the family genetic risk scores (FGRS) for alcohol use disorder (AUD) and major depression (MD), their interaction with each other and with the relevant comorbid disorder on risk for AUD and MD. FGRS scores are constructed using rates of illness in first-fourth degree relatives. FGRS for AUD and MD interacted in predicting of both disorders and one FRGS (e.g., for AUD) interacted with the phenotype of MD to predict that disorder (e.g., AUD). These FGRS interactions were not substantially attenuated by adding interactions with the disorders. These results replicated across sexes. In predicting risk for a given disorder, we rarely consider genetic liabilities for other disorders. But such effects were here significant and interactive. Furthermore, the primary disorder genetic risk interacts with comorbid disorders. The pathways to risk for disorders from their and other disorders' genetic liability may be more complex than commonly considered.</p>}},
author = {{Kendler, Kenneth S. and Lönn, Sara L. and Sundquist, Jan and Sundquist, Kristina}},
issn = {{1552-4841}},
keywords = {{alcohol use disorder; family genetic risk score; interactions; major depression}},
language = {{eng}},
number = {{5}},
pages = {{128--138}},
publisher = {{International Society of Psychiatric Genetics}},
series = {{American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics}},
title = {{The actions and interactions of family genetic risk scores for alcohol use disorder and major depression on the risk for these two disorders}},
url = {{http://dx.doi.org/10.1002/ajmg.b.32909}},
doi = {{10.1002/ajmg.b.32909}},
volume = {{189}},
year = {{2022}},
}