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Genetic nurture effects for alcohol use disorder

Molecular Psychiatry volume 28, pages 759–766 (2023)Cite this article

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Abstract

We tested whether aspects of the childhood/adolescent home environment mediate genetic risk for alcohol problems within families across generations. Parental relationship discord and parental divorce were the focal environments examined. The sample included participants of European ancestry (N = 4806, 51% female) and African ancestry (N = 1960, 52% female) from the high-risk Collaborative Study on the Genetics of Alcoholism. Alcohol outcomes in the child generation included lifetime criterion counts for DSM-5 Alcohol Use Disorder (AUD), lifetime maximum drinks in 24 h, age at initiation of regular drinking, and age at first alcohol intoxication. Predictors in the parent generation included relationship discord, divorce, alcohol measures parallel to those in the child generation, and polygenic scores for alcohol problems. Parental polygenic scores were partitioned into alleles that were transmitted and non-transmitted to the child. The results from structural equation models were consistent with genetic nurture effects in European ancestry families. Exposure to parental relationship discord and parental divorce mediated, in part, the transmission of genetic risk for alcohol problems from parents to children to predict earlier ages regular drinking (βindirect = −0.018 [−0.026, −0.011]) and intoxication (βindirect = −0.015 [−0.023, −0.008]), greater lifetime maximum drinks (βindirect = 0.006 [0.002, 0.01]) and more lifetime AUD criteria (βindirect = 0.011 [0.006, 0.016]). In contrast, there was no evidence that parental alleles had indirect effects on offspring alcohol outcomes via parental relationship discord or divorce in the smaller number of families of African ancestry. In conclusion, parents transmit genetic risk for alcohol problems to their children not only directly, but also indirectly via genetically influenced aspects of the home environment. Further investigation of genetic nurture in non-European samples is needed.

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Fig. 1: Illustrative extended nature of nurture model for AUDSx (DSM-5 Alcohol Use Disorder Criterion Count) depicting parental divorce and parental AUDSx as mediators of genetic risk across generations.

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Acknowledgements

The Collaborative Study on the Genetics of Alcoholism (COGA), Principal Investigators B. Porjesz, V. Hesselbrock, T. Foroud; Scientific Director, A. Agrawal; Translational Director, DD, includes eleven different centers: University of Connecticut (VH); Indiana University (HJE, TF, YL, MP); University of Iowa Carver College of Medicine (SK, JK); SUNY Downstate Health Sciences University (BP, JM, CK, AP); Washington University in St. Louis (LB, JR, KB, AA); University of California at San Diego (MS); Rutgers University (JT, RH, JS); The Children’s Hospital of Philadelphia, University of Pennsylvania (LA); Virginia Commonwealth University (DD); Icahn School of Medicine at Mount Sinai (AG, PS); and Howard University (DS). Other COGA collaborators include: L Bauer (University of Connecticut); J. Nurnberger Jr., L. Wetherill, X., Xuei, D. Lai, S. O’Connor, (Indiana University); GC (University of Iowa; University of Connecticut); D.B. Chorlian, J. Zhang, P. Barr, S. Kinreich, G. Pandey (SUNY Downstate); N. Mullins (Icahn School of Medicine at Mount Sinai); A. Anokhin, S. Hartz, E. Johnson, V. McCutcheon, S. Saccone (Washington University); J. Moore, Z. Pang, S. Kuo (Rutgers University); A. Merikangas (The Children’s Hospital of Philadelphia and University of Pennsylvania); F. Aliev (Virginia Commonwealth University); H. Chin and A. Parsian are the NIAAA Staff Collaborators. We continue to be inspired by our memories of Henri Begleiter and Theodore Reich, founding PI and Co-PI of COGA, and also owe a debt of gratitude to other past organizers of COGA, including Ting- Kai Li, P. Michael Conneally, Raymond Crowe, and Wendy Reich, for their critical contributions. This national collaborative study is supported by NIH Grant U10AA008401 from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the National Institute on Drug Abuse (NIDA). Additional support for this project came from NIAAA award R01AA028064 to JES. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Author information

Author notes

  1. These authors contributed equally: Nathaniel S. Thomas, Jessica E. Salvatore.

Authors and Affiliations

  1. Department of Psychology, Virginia Commonwealth University, Richmond, VA, USA

    Nathaniel S. Thomas

  2. Department of Psychiatry, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ, USA

    Jessica E. Salvatore, Sally I-Chun Kuo, Fazil Aliev, Sarah J. Brislin & Danielle M. Dick

  3. Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA

    Vivia V. McCutcheon, Kathleen K. Bucholz, Arpana Agrawal, Laura Bierut & John Rice

  4. Department of Psychiatry and Behavioral Sciences, State University of New York Health Sciences University, Brooklyn, NY, USA

    Jacquelyn M. Meyers, Chella Kamarajan, Gayathri Pandey, Bernice Porjesz & Ashwini Pandey

  5. Department of Psychiatry, University of Connecticut School of Medicine, Farmington, CT, USA

    Grace Chan & Victor Hesselbrock

  6. Department of Psychiatry, University of Iowa, Iowa City, IA, USA

    Grace Chan, John R. Kramer & Samuel Kuperman

  7. Department of Biochemistry and Molecular Biology, Indiana University, Indianapolis, IN, USA

    Howard J. Edenberg

  8. Department of Psychiatry, Indiana University, Indianapolis, IN, USA

    Martin H. Plawecki

  9. Department of Psychiatry, University of California San Diego Medical School, San Diego, CA, USA

    Marc A. Schuckit

  10. Department of Medical & Molecular Genetics, Indiana University, Indianapolis, IN, USA

    Tatiana Foroud

  11. Departments of Medical & Molecular Genetics, Biostatistics, and BioHealth Informatics, Indiana University, Indianapolis, IN, USA

    Yunlong Liu

  12. Department of Genetics, Rutgers University, Piscataway, NJ, USA

    Jay Tischfield

  13. Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ, USA

    Ronald Hart

  14. The Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA, USA

    Laura Almasy

  15. Departments of Genetics and Genomic Sciences, Neuroscience, and Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Alison Goate

  16. Departments of Neuroscience and Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Paul Slesinger

  17. Department of Pediatrics, Howard University, Washington DC, USA

    Denise Scott

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  1. Nathaniel S. Thomas
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Consortia

COGA Collaborators

  • Bernice Porjesz
  • , Victor Hesselbrock
  • , Tatiana Foroud
  • , Arpana Agrawal
  • , Danielle M. Dick
  • , Howard J. Edenberg
  • , Yunlong Liu
  • , Martin H. Plawecki
  • , Samuel Kuperman
  • , John R. Kramer
  • , Jacquelyn M. Meyers
  • , Chella Kamarajan
  • , Ashwini Pandey
  • , Laura Bierut
  • , John Rice
  • , Kathleen K. Bucholz
  • , Marc A. Schuckit
  • , Jay Tischfield
  • , Ronald Hart
  • , Jessica E. Salvatore
  • , Laura Almasy
  • , Alison Goate
  • , Paul Slesinger
  •  & Denise Scott

Contributions

Data curation: NST, SIK, FA. Formal analysis: NST, FA. Conceptualization NST, JES. Writing – Original Draft: NST, JES. Writing – review & editing: NST, JES, SIK, FA, VVM, JMM, KKB, SJB, GC, HJE, CK, JRK, SK, GP, MHP, MAS, DMD. Conception and Design of the COGA Study (COGA Collaborators).

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Correspondence to Nathaniel S. Thomas or Jessica E. Salvatore.

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Thomas, N.S., Salvatore, J.E., Kuo, S.IC. et al. Genetic nurture effects for alcohol use disorder. Mol Psychiatry 28, 759–766 (2023). https://doi.org/10.1038/s41380-022-01816-z

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