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The Impact of the Parental Patterns of Morbidity and Comorbidity in the Cross-Generational Transmission of Risk for Major Depression and Alcohol Use Disorder

Kendler, Kenneth S ; Abrahamsson, Linda LU ; Sundquist, Jan LU and Sundquist, Kristina LU (2025) In American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Abstract

To further understand the inter-relationship of the familial transmission of major depression (MD) and alcohol use disorder (AUD), we examine, via a multivariable Cox proportional hazards model, risks for AUD and MD in 1,244,516 individuals born in Sweden from 1970 to 1990 to intact mother-father pairs as a function of parental diagnoses of MD and/or AUD. Across the nine possible mating types, we see both direct transmission (MD → MD, AUD → AUD) and also, less strongly, indirect transmission: MD → AUD and AUD → MD. Risks in offspring accumulate with multiple affected parents, which reveals the impact of interactive effects in risk prediction. Interestingly, the risk for comorbid AUD/MD in offspring is higher when one parent has MD and... (More)

To further understand the inter-relationship of the familial transmission of major depression (MD) and alcohol use disorder (AUD), we examine, via a multivariable Cox proportional hazards model, risks for AUD and MD in 1,244,516 individuals born in Sweden from 1970 to 1990 to intact mother-father pairs as a function of parental diagnoses of MD and/or AUD. Across the nine possible mating types, we see both direct transmission (MD → MD, AUD → AUD) and also, less strongly, indirect transmission: MD → AUD and AUD → MD. Risks in offspring accumulate with multiple affected parents, which reveals the impact of interactive effects in risk prediction. Interestingly, the risk for comorbid AUD/MD in offspring is higher when one parent has MD and the other AUD rather than when one parent has both disorders. Modest sex effects are seen, with maternal-offspring transmission sometimes significantly stronger than paternal-offspring transmission. In most comparisons, parental-offspring transmission was modestly stronger for same-sex versus opposite-sex parent-offspring pairs. These results suggest that MD/AUD comorbidity in Sweden is due, at least in part, to correlated familial liability transmitted by direct and indirect paths across generations. We could reject the hypothesis that an AUD/MD syndrome was specifically transmitted from parents to offspring.

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Contribution to journal
publication status
epub
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in
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
publisher
Wiley-Liss Inc.
external identifiers
  • pmid:40813350
ISSN
1552-4841
DOI
10.1002/ajmg.b.33052
language
English
LU publication?
yes
additional info
© 2025 The Author(s). American Journal of Medical Genetics Part B: Neuropsychiatric Genetics published by Wiley Periodicals LLC.
id
9c42cd00-b3c4-40e9-bda7-debe141d8fe4
date added to LUP
2025-08-18 12:49:07
date last changed
2025-08-18 12:49:07
@article{9c42cd00-b3c4-40e9-bda7-debe141d8fe4,
  abstract     = {{<p>To further understand the inter-relationship of the familial transmission of major depression (MD) and alcohol use disorder (AUD), we examine, via a multivariable Cox proportional hazards model, risks for AUD and MD in 1,244,516 individuals born in Sweden from 1970 to 1990 to intact mother-father pairs as a function of parental diagnoses of MD and/or AUD. Across the nine possible mating types, we see both direct transmission (MD → MD, AUD → AUD) and also, less strongly, indirect transmission: MD → AUD and AUD → MD. Risks in offspring accumulate with multiple affected parents, which reveals the impact of interactive effects in risk prediction. Interestingly, the risk for comorbid AUD/MD in offspring is higher when one parent has MD and the other AUD rather than when one parent has both disorders. Modest sex effects are seen, with maternal-offspring transmission sometimes significantly stronger than paternal-offspring transmission. In most comparisons, parental-offspring transmission was modestly stronger for same-sex versus opposite-sex parent-offspring pairs. These results suggest that MD/AUD comorbidity in Sweden is due, at least in part, to correlated familial liability transmitted by direct and indirect paths across generations. We could reject the hypothesis that an AUD/MD syndrome was specifically transmitted from parents to offspring.</p>}},
  author       = {{Kendler, Kenneth S and Abrahamsson, Linda and Sundquist, Jan and Sundquist, Kristina}},
  issn         = {{1552-4841}},
  language     = {{eng}},
  month        = {{08}},
  publisher    = {{Wiley-Liss Inc.}},
  series       = {{American Journal of Medical Genetics Part B: Neuropsychiatric Genetics}},
  title        = {{The Impact of the Parental Patterns of Morbidity and Comorbidity in the Cross-Generational Transmission of Risk for Major Depression and Alcohol Use Disorder}},
  url          = {{http://dx.doi.org/10.1002/ajmg.b.33052}},
  doi          = {{10.1002/ajmg.b.33052}},
  year         = {{2025}},
}