GWAS and systems biology analysis of depressive symptoms among smokers from the COPDGene cohort.
J Affect Disord
; 243: 16-22, 2019 01 15.
Article
en En
| MEDLINE
| ID: mdl-30219690
ABSTRACT
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 (pâ¯=â¯1.28â¯×â¯10-6), is near CHRM3. Another SNP was near MDGA2 (rs17118176, pâ¯=â¯3.52â¯×â¯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 (pâ¯=â¯1.00â¯×â¯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.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Fumar
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Depresión
Tipo de estudio:
Diagnostic_studies
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Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Año:
2019
Tipo del documento:
Article