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

• Published in: Experimental & molecular medicine 2018, 50(0), , pp.1-7
• Main Authors: Park, Heung-Woo, Song, Woo-Jung, Cho, Sang-Heon, McGeachie, Michael J., Martinez, Fernando, Mauger, Dave, Bender, Bruce G., Tantisira, Kelan G.
• Format: Article
• Language: English
• Subjects: 38/43; 631/208; 692/699/1785/31; Aged; Alleles; Anxiety; Asthma; Asthma - epidemiology; Asthma - genetics; Bayesian analysis; Biomedical and Life Sciences; Biomedicine; Child; Childhood; Children; Depression - epidemiology; Depression - genetics; ErbB-2 protein; Female; Gene mapping; Genetic factors; Genome-wide association studies; Geriatrics; Homozygote; Humans; Kinases; Male; Medical Biochemistry; Mental depression; Molecular Medicine; Polymorphism, Single Nucleotide; Protein-tyrosine kinase receptors; Receptor, ErbB-4 - genetics; Single-nucleotide polymorphism; Stem Cells; 생화학
• ISSN: 1226-3613; 2092-6413
• DOI: 10.1038/s12276-018-0110-5

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. Asthma: How genetic factors and depression affect symptom severity A novel mutation affects how depression influences the severity of asthma symptoms, with opposite effects in children and the elderly. Depression is known to affect the severity of symptoms experienced by patients with chronic disorders, such as asthma. Heung-Woo Park at Seoul National University College of Medicine in South Korea and coworkers investigated how genetic factors might influence the interaction between depression and asthma. Using previously collected genetic data, the researchers identified a mutation linked with both asthma and depression