Heritable Composite Phenotypes Defined by Combinations of Conduct Problem, Depression, and Temperament Features: Contributions to risk for Alcohol Problems.

Frances L Wang, Lambertus Klei, Bernie Devlin, Brooke S G Molina, Laurie Chassin
Author Information
  1. Frances L Wang: Department of Psychiatry, University of Pittsburgh, 3811 O'Hara St, Pittsburgh, PA, 15213, USA. wangfl@upmc.edu.
  2. Lambertus Klei: Department of Psychiatry, University of Pittsburgh, 3811 O'Hara St, Pittsburgh, PA, 15213, USA.
  3. Bernie Devlin: Department of Psychiatry, University of Pittsburgh, 3811 O'Hara St, Pittsburgh, PA, 15213, USA.
  4. Brooke S G Molina: Department of Psychiatry, University of Pittsburgh, 3811 O'Hara St, Pittsburgh, PA, 15213, USA.
  5. Laurie Chassin: Department of Psychology, Arizona State University, Tempe, AZ, 85281, USA.

Abstract

The genetic architectures underlying symptoms of conduct problems and depression have largely been examined separately and without incorporating temperament, despite evidence for their genetic overlap. We examined how symptoms and temperament dimensions were transmitted together in families to identify highly heritable composite phenotypes, and how these composite phenotypes predicted alcohol outcomes in young adulthood. Participants (N���=���486) were drawn from the third generation of families oversampled for alcohol use disorder in the first generation. Conduct problems, depression, and temperament were reported at 11-19 years old and alcohol outcomes at 18-26 years old. Using principal components of heritability analysis, we found seven highly heritable composite phenotypes, five of which predicted alcohol outcomes: three characterized by co-occurring conduct problems and depression and two by conduct problems. Novel composite phenotypes that were characterized by both conduct problems and depression showed different types of symptoms, temperament features, and genetic underpinnings. Children manifesting differing composite phenotypes might benefit from distinct treatments based on their unique etiologies.

Keywords

References

  1. Stat Appl Genet Mol Biol. 2012 Jan 06;11(2): [PMID: 22499698]
  2. J Am Acad Child Adolesc Psychiatry. 2010 Mar;49(3):248-55 [PMID: 20410714]
  3. J Stud Alcohol. 1992 Jul;53(4):316-9 [PMID: 1619925]
  4. J Child Psychol Psychiatry. 2011 Jul;52(7):792-9 [PMID: 21039488]
  5. Psychol Serv. 2018 Feb;15(1):65-77 [PMID: 28517951]
  6. Annu Rev Psychol. 1997;48:371-410 [PMID: 9046564]
  7. J Am Acad Child Adolesc Psychiatry. 2011 Aug;50(8):818-27 [PMID: 21784301]
  8. JAMA Psychiatry. 2013 Jan;70(1):78-86 [PMID: 23117573]
  9. JAMA Psychiatry. 2013 Jun;70(6):599-607 [PMID: 23740048]
  10. Nat Hum Behav. 2019 May;3(5):513-525 [PMID: 30962613]
  11. Infant Child Dev. 2008 Aug;17(4):365-385 [PMID: 27076792]
  12. J Abnorm Psychol. 2017 May;126(4):454-477 [PMID: 28333488]
  13. Cell. 2019 Dec 12;179(7):1469-1482.e11 [PMID: 31835028]
  14. Nat Hum Behav. 2018 Jul;2(7):514-521 [PMID: 31097806]
  15. Science. 2022 Nov 18;378(6621):709-710 [PMID: 36395208]
  16. Dev Psychol. 2010 Sep;46(5):1159-75 [PMID: 20822230]
  17. Behav Res Ther. 2000 Aug;38(8):835-55 [PMID: 10937431]
  18. J Abnorm Psychol. 1998 Feb;107(1):27-37 [PMID: 9505036]
  19. PLoS One. 2016 Jun 06;11(6):e0156744 [PMID: 27271781]
  20. J Consult Clin Psychol. 2003 Jun;71(3):465-81 [PMID: 12795571]
  21. Dev Psychopathol. 2021 Dec;33(5):1584-1598 [PMID: 34365985]
  22. Soc Sci Res. 2014 Jan;43:184-99 [PMID: 24267761]
  23. Schizophr Bull. 2013 Mar;39(2):464-71 [PMID: 22234486]
  24. J Abnorm Child Psychol. 2008 Apr;36(3):433-44 [PMID: 17965930]
  25. J Child Psychol Psychiatry. 2006 Mar-Apr;47(3-4):395-422 [PMID: 16492265]
  26. J Abnorm Psychol. 2011 Aug;120(3):644-655 [PMID: 21574666]
  27. World Psychiatry. 2020 Oct;19(3):350-359 [PMID: 32931100]
  28. Hum Hered. 1999 Mar;49(2):106-11 [PMID: 10077732]
  29. J Abnorm Psychol. 2020 Feb;129(2):143-161 [PMID: 31804095]
  30. Nat Genet. 2022 May;54(5):548-559 [PMID: 35513722]
  31. Am J Psychiatry. 2014 Apr;171(4):395-7 [PMID: 24687194]
  32. Psychol Bull. 2002 May;128(3):490-529 [PMID: 12002699]
  33. Dev Psychopathol. 2013 Nov;25(4 Pt 2):1567-84 [PMID: 24342856]

Grants

  1. K01 AA027757/NIAAA NIH HHS
  2. R01 AA016213/NIAAA NIH HHS
  3. AA016213/NIAAA NIH HHS
  4. AA027757/NIAAA NIH HHS

MeSH Term

Child
Humans
Young Adult
Adult
Adolescent
Depression
Temperament
Problem Behavior
Alcoholism
Ethanol
Phenotype

Chemicals

Ethanol

Word Cloud

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