| Autor: |
Palmer RHC; Behavioral Genetics of Addiction Laboratory, Department of Psychology, Emory University, Atlanta, GA, USA. Rohan.Palmer@Emory.edu., Benca-Bachman CE; Behavioral Genetics of Addiction Laboratory, Department of Psychology, Emory University, Atlanta, GA, USA., Huggett SB; Behavioral Genetics of Addiction Laboratory, Department of Psychology, Emory University, Atlanta, GA, USA., Bubier JA; The Jackson Laboratory, Bar Harbor, ME, USA., McGeary JE; Department of Psychiatry and Human Behavior, Brown University, Providence, RI, USA.; Providence Veterans Affairs Medical Center, Providence, RI, USA., Ramgiri N; Behavioral Genetics of Addiction Laboratory, Department of Psychology, Emory University, Atlanta, GA, USA., Srijeyanthan J; Behavioral Genetics of Addiction Laboratory, Department of Psychology, Emory University, Atlanta, GA, USA., Yang J; Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA., Visscher PM; Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia., Yang J; Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia., Knopik VS; Department of Human Development and Family Studies, Purdue University, West Lafayette, IN, USA., Chesler EJ; The Jackson Laboratory, Bar Harbor, ME, USA. |
| Abstrakt: |
Cross-species translational approaches to human genomic analyses are lacking. The present study uses an integrative framework to investigate how genes associated with nicotine use in model organisms contribute to the genetic architecture of human tobacco consumption. First, we created a model organism geneset by collecting results from five animal models of nicotine exposure (RNA expression changes in brain) and then tested the relevance of these genes and flanking genetic variation using genetic data from human cigarettes per day (UK BioBank N = 123,844; all European Ancestry). We tested three hypotheses: (1) DNA variation in, or around, the 'model organism geneset' will contribute to the heritability to human tobacco consumption, (2) that the model organism genes will be enriched for genes associated with human tobacco consumption, and (3) that a polygenic score based off our model organism geneset will predict tobacco consumption in the AddHealth sample (N = 1667; all European Ancestry). Our results suggested that: (1) model organism genes accounted for ~5-36% of the observed SNP-heritability in human tobacco consumption (enrichment: 1.60-31.45), (2) model organism genes, but not negative control genes, were enriched for the gene-based associations (MAGMA, H-MAGMA, SMultiXcan) for human cigarettes per day, and (3) polygenic scores based on our model organism geneset predicted cigarettes per day in an independent sample. Altogether, these findings highlight the advantages of using multiple species evidence to isolate genetic factors to better understand the etiological complexity of tobacco and other nicotine consumption. |
