GWAS and systems biology analysis of depressive symptoms among smokers from the COPDGene cohort.

Autor: Heinzman JT; Department of Psychiatry, University of Iowa Hospitals and Clinics, Iowa City, IA, USA., Hoth KF; Department of Psychiatry, University of Iowa Hospitals and Clinics, Iowa City, IA, USA., Cho MH; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA., Sakornsakolpat P; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA., Regan EA; Department of Medicine, National Jewish Health, Denver, CO, USA; Department of Epidemiology, Colorado School of Public Health, University of Colorado, Aurora, CO, USA., Make BJ; Department of Medicine, National Jewish Health, Denver, CO, USA., Kinney GL; Department of Epidemiology, Colorado School of Public Health, University of Colorado, Aurora, CO, USA., Wamboldt FS; Department of Medicine, National Jewish Health, Denver, CO, USA; Department of Psychiatry, University of Colorado School of Medicine at the Anschutz Medical Campus, Aurora, CO, USA., Holm KE; Department of Medicine, National Jewish Health, Denver, CO, USA., Bormann N; Department of Psychiatry, University of Iowa Hospitals and Clinics, Iowa City, IA, USA., Robles J; Department of Psychiatry, University of Iowa Hospitals and Clinics, Iowa City, IA, USA., Kim V; Department of Thoracic Medicine and Surgery, Temple University School of Medicine, Philadelphia, PA, USA., Iyer AS; Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA; Lung Health Center, University of Alabama at Birmingham, Birmingham, AL, USA; Health Services, Outcomes, and Effectiveness Research Training Program, University of Alabama at Birmingham, Birmingham, AL, USA., Silverman EK; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA., Crapo JD; Department of Medicine, National Jewish Health, Denver, CO, USA., Han S; Department of Psychiatry, University of Iowa Hospitals and Clinics, Iowa City, IA, USA; Department of Psychiatry, Johns Hopkins University, Baltimore, MD, USA., Potash JB; Department of Psychiatry, University of Iowa Hospitals and Clinics, Iowa City, IA, USA; Department of Psychiatry, Johns Hopkins University, Baltimore, MD, USA., Shinozaki G; Department of Psychiatry, University of Iowa Hospitals and Clinics, Iowa City, IA, USA. Electronic address: gen-shinozaki@uiowa.edu.
Jazyk: angličtina
Zdroj: Journal of affective disorders [J Affect Disord] 2019 Jan 15; Vol. 243, pp. 16-22. Date of Electronic Publication: 2018 Sep 07.
DOI: 10.1016/j.jad.2018.09.003
Abstrakt: Background: Large sample GWAS is needed to identify genetic factors associated with depression. This study used genome-wide genotypic and phenotypic data from the COPDGene study to identify genetic risk factors for depression.
Methods: Data were from 9716 COPDGene subjects with ≥10 pack-year history. Depression was defined as antidepressant use and/or a HADS depression subscale score ≥8. Non-Hispanic White (6576) and African-American (3140) subsets were analyzed. A GWAS pipeline identified SNPs associated with depression in each group. Network analysis software analyzed gene interactions through common biological pathways, genetic interactions, and tissue-specific gene expression.
Results: The mean age was 59.4 years (SD 9.0) with 46.5% female subjects. Depression was in 24.7% of the NHW group (1622) and 12.5% of the AA group (391). No SNPs had genome-wide significance. One of the top SNPs, rs12036147 (p = 1.28 × 10 -6 ), is near CHRM3. Another SNP was near MDGA2 (rs17118176, p = 3.52 × 10 -6 ). Top genes formed networks for synaptic transmission with a statistically significant level of more co-expression in brain than other tissues, particularly in the basal ganglia (p = 1.00 × 10 -4 ).
Limitations: Limitations included a depression definition based on antidepressant use and a limited HADS score subgroup, which could increase false negatives in depressed patients not on antidepressants. Antidepressants used for smoking cessation in non-depressed patients could lead to false positives.
Conclusions: Systems biology analysis identified statistically significant pathways whereby multiple genes influence depression. The gene set pathway analysis and COPDGene data can help investigate depression in future studies.
(Copyright © 2018 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: