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Assessment of genetic factor and depression interactions for asthma symptom severity in cohorts of childhood and elderly asthmatics.

ABSTRACT: It is well known that depression is associated with asthma symptoms. We assessed the combined effects of genetic factors and depression on asthma symptom severity using Bayesian network (BN) analysis. The common 100 top-ranked single-nucleotide polymorphisms (SNPs) were obtained from two genome-wide association studies of symptom severity in two childhood asthmatics trials (CAMP (Childhood Asthma Management Program) and CARE (Childhood Asthma Research and Education)). Using SNPs plus five discretized variables (depression, anxiety, age, sex, and race), we performed BN analysis in 529 CAMP subjects. We identified two nodes (depression and rs4672619 mapping to ERBB4 (Erb-B2 receptor tyrosine kinase 4)) that were within the Markov neighborhood of the symptom node in the network and then evaluated the interactive effects of depressive status and rs4672619 genotypes on asthma symptom severity. In childhood asthmatics with homozygous reference alleles, severe depression was related to less severe symptoms. However, in childhood asthmatics with heterozygous alleles and homozygous variant alleles, depression and symptom severity showed a positive correlation (interaction permutation P value?=?0.019). We then tried to evaluate whether the interactive effects that we found were sustained in another independent cohort of elderly asthmatics. Contrary to the findings from childhood asthmatics, elderly asthmatics with homozygous reference alleles showed a positive correlation between depression and symptom severity, and elderly asthmatics with heterozygous alleles and homozygous variant alleles showed a negative correlation (interaction permutation P value?=?0.003). In conclusion, we have identified a novel SNP, rs4672619, that shows interactive effects with depression on asthma symptom severity in childhood and elderly asthmatics in opposite directions.

SUBMITTER: Park HW

PROVIDER: S-EPMC6031659 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Assessment of genetic factor and depression interactions for asthma symptom severity in cohorts of childhood and elderly asthmatics.

Park Heung-Woo HW Song Woo-Jung WJ Cho Sang-Heon SH McGeachie Michael J MJ Martinez Fernando F Mauger Dave D Bender Bruce G BG Tantisira Kelan G KG

Experimental & molecular medicine 20180704 7

It is well known that depression is associated with asthma symptoms. We assessed the combined effects of genetic factors and depression on asthma symptom severity using Bayesian network (BN) analysis. The common 100 top-ranked single-nucleotide polymorphisms (SNPs) were obtained from two genome-wide association studies of symptom severity in two childhood asthmatics trials (CAMP (Childhood Asthma Management Program) and CARE (Childhood Asthma Research and Education)). Using SNPs plus five discre ...[more]

PMID: 29973587

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Project description:BackgroundAn automated web-based assessment and monitoring system ( www.psynary.com ) has been developed to assist non-specialist clinicians in managing common mood and anxiety disorders. Psynary promotes the use of standardised outcome measures to assess symptom severity and optimise treatments with the aim of improving outcomes and enabling faster recovery. This paper analyses the results from two parallel studies in New Zealand and Japan (OptiMA-1 NZ and Japan) to assess the validity of the R8 Depression scale, one of the system's core outcome measures.MethodsClinical samples were recruited from a public secondary care and a private psychiatry clinic. Participants completed the outcome measures for the study via the online Psynary system. The R8 Depression scale is a 30-item questionnaire which includes all symptom domains covered in the ICD-10 classification of depression. The Patient Health Questionnaire (PHQ-9) was completed at the same time points as the R8 Depression, with a smaller sample also completing a paper-based Quick Inventory of Depressive Symptomatology (QIDS-SR16). Internal validity was quantified via Cronbach's alpha and Guttman lower bounds method. External validation against the PHQ-9 and QIDS used the Pearson's and Kendall's correlation coefficients. Severity categories were set using a multivariate regression model.Results270 patients participated in the study and completed a maximum of 1 baseline and 5 reviews within a 90-day period, giving a total of 1124 assessments with the PHQ-9 also being completed in 1053 of these assessments. R8 Depression normative data was also collected from 204 non-clinical volunteers with 187 of these also completing the PHQ9. Internal reliability scores were all higher than 0.9 (n = 1328). There was overall good external validity when comparing the R8 Depression to the PHQ-9, with a correlation of 0.91 for the combined normative and clinical samples (n = 1240).ConclusionsThe R8 Depression has been developed as a patient-rated outcome measure for depression for administration on an online system called "Psynary". It has high internal and external validity against current widely used scales. Further work is underway to determine the sensitivity to change of the R8 Depression.

Dataset Information

Assessment of genetic factor and depression interactions for asthma symptom severity in cohorts of childhood and elderly asthmatics.

Publications

Assessment of genetic factor and depression interactions for asthma symptom severity in cohorts of childhood and elderly asthmatics.

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