Novel characterization of the multivariate genetic architecture of internalizing psychopathology and alcohol use.
| Title: | Novel characterization of the multivariate genetic architecture of internalizing psychopathology and alcohol use. |
|---|---|
| Authors: | Colbert SMC; Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, Colorado, USA.; Department of Ecology and Evolutionary Biology, University of Colorado Boulder, Boulder, Colorado, USA.; Funkhouser SA; Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, Colorado, USA.; Johnson EC; Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA.; Morrison CL; Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, Colorado, USA.; Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, Colorado, USA.; Hoeffer CA; Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, Colorado, USA.; Department of Integrative Physiology, University of Colorado Boulder, Boulder, Colorado, USA.; Friedman NP; Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, Colorado, USA.; Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, Colorado, USA.; Ehringer MA; Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, Colorado, USA.; Department of Integrative Physiology, University of Colorado Boulder, Boulder, Colorado, USA.; Evans LM; Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, Colorado, USA.; Department of Ecology and Evolutionary Biology, University of Colorado Boulder, Boulder, Colorado, USA. |
| Source: | American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics [Am J Med Genet B Neuropsychiatr Genet] 2021 Sep; Vol. 186 (6), pp. 353-366. Date of Electronic Publication: 2021 Sep 27. |
| Publication Type: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
| Language: | English |
| Journal Info: | Publisher: Wiley-Blackwell Country of Publication: United States NLM ID: 101235742 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1552-485X (Electronic) Linking ISSN: 15524841 NLM ISO Abbreviation: Am J Med Genet B Neuropsychiatr Genet Subsets: MEDLINE |
| Imprint Name(s): | Publication: Hoboken, N.J. : Wiley-Blackwell; Original Publication: Hoboken, N.J. : Wiley-Liss, c2003- |
| MeSH Terms: | Alcoholism*/genetics ; Genome-Wide Association Study*; Alcohol Drinking/genetics ; Humans ; Psychopathology |
| Abstract: | Genetic correlations suggest that the genetic relationship of alcohol use with internalizing psychopathology depends on the measure of alcohol use. Problematic alcohol use (PAU) is positively genetically correlated with internalizing psychopathology, whereas alcohol consumption ranges from not significantly correlated to moderately negatively correlated with internalizing psychopathology. To explore these different genetic relationships of internalizing psychopathology with alcohol use, we performed a multivariate genome-wide association study of four correlated factors (internalizing psychopathology, PAU, quantity of alcohol consumption, and frequency of alcohol consumption) and then assessed genome-wide and local genetic covariance between these factors. We identified 14 significant regions of local, largely positive, genetic covariance between PAU and internalizing psychopathology and 12 regions of significant local genetic covariance (including both positive and negative genetic covariance) between consumption factors and internalizing psychopathology. Partitioned genetic covariance among functional annotations suggested that brain tissues contribute significantly to positive genetic covariance between internalizing psychopathology and PAU but not to the genetic covariance between internalizing psychopathology and quantity or frequency of alcohol consumption. We hypothesize that genome-wide genetic correlations between alcohol use and psychiatric traits may not capture the more complex shared or divergent genetic architectures at the locus or tissue specific level. This study highlights the complexity of genetic architectures of alcohol use and internalizing psychopathology, and the differing shared genetics of internalizing disorders with PAU compared to consumption.; (© 2021 Wiley Periodicals LLC.) |
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| Grant Information: | R01 AG046938 United States AG NIA NIH HHS; R01 DA042742 United States DA NIDA NIH HHS; U01 DA046413 United States DA NIDA NIH HHS; U01 MH109532 United States MH NIMH NIH HHS; R01 MH100141 United States MH NIMH NIH HHS; R01 NS086933 United States NS NINDS NIH HHS; T32 MH016880 United States MH NIMH NIH HHS; F32 AA027435 United States AA NIAAA NIH HHS |
| Contributed Indexing: | Keywords: genetic risk; genome-wide association studies; internalizing psychopathology; problematic alcohol use; substance use |
| Entry Date(s): | Date Created: 20210927 Date Completed: 20220113 Latest Revision: 20240925 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC8556277 |
| DOI: | 10.1002/ajmg.b.32874 |
| PMID: | 34569141 |
| Database: | MEDLINE |
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.