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Exp Mol Med. 2018;50(7):1-7.

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

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제1저자 박흥우 · 교신저자 박흥우

PMID 29973587 PMC6031659 DOI 10.1038/s12276-018-0110-5 IF 17.5 알레르기내과
소속 (8)
  1. Department of Medicine, Channing Division of Network of Medicine, Brigham and Womens Hospital, Harvard Medical School, Boston, MA, USA. guinea71@snu.ac.kr.
  2. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea. guinea71@snu.ac.kr.
  3. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
  4. Department of Medicine, Channing Division of Network of Medicine, Brigham and Womens Hospital, Harvard Medical School, Boston, MA, USA.
  5. Arizona Respiratory Center, University of Arizona, Tucson, AZ, USA.
  6. Department of Public Health Sciences, Pennsylvania State University College of Medicine, Hershey, PA, USA.
  7. National Jewish Health, Denver, CO, USA.
  8. Department of Medicine, Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA.

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.

Figures

Fig. 1
Fig. 1 Bayesian network inferred. A Bayesian network learned from the data of childhood asthmatics with a Hill-Climbing algorithm. Edges represent conditional dependencies, and connected nodes represent variables that are conditionally dependent on each other. Red edges represent edges with an arc strength >0.5, blue edges represent edges with an arc strength between 0.2 and 0.5, and black edges represent edges with an arc strength between 0.1 and 0.2. Edges with an arc strength <0.1 were removed from the network. For a certain node, nodes connected above (parent nodes), nodes connected below (children nodes), and the other parent nodes of these children nodes form a Markov blanket, which is required to predict the behavior of that node. Thus, we evaluated the interactive effects of depression severity (parent of the Sx node) and rs4672619 (S16) genotypes (children of the Sx node) on asthma symptom severity (Sx node). A age quartile, Ax anxiety quartile, Dp depression quartile, G gender (male/female), Sx symptom severity quartile, R ethnicity (non-Hispanic white/African American/Hispanic/Asian), and S1-100 top-ranked 100 SNPs (S16, rs4672619)
Fig. 2
Fig. 2 Interactive effects of rs4672619 genotypes and depression severity on asthma symptom severity in cohorts of childhood and elderly asthmatics. a Childhood asthmatics. b Elderly asthmatics. Solid lines represent subjects with reference homozygous alleles of rs4672619, and dotted lines represent subjects with heterozygous or homozygous variant alleles of rs4672619. Q1 represents mild depression, and Q4 represents severe depression. The severity of asthma symptoms increases as symptom score increases

그림 출처: PubMed Central 공개 논문 (PMC6031659)

Conflict of interest statement

The authors declare that they have no conflict of interest.

그 밖의 정보
출판 형태
Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
저널
Experimental & molecular medicine · eISSN 2092-6413
전자 출판
2018-07-04
MeSH
Aged · Asthma / epidemiology / genetics · Child · Depression / epidemiology / genetics · Female · Homozygote · Humans · Male · Polymorphism, Single Nucleotide* · Receptor, ErbB-4 / genetics
Substances
ERBB4 protein, human · Receptor, ErbB-4
연구비
NHLBI NIH HHS U01 HL065899 · NINR NIH HHS R01 NR013391 · NIH HHS R01 NR013391 and U01 HL065899 · NIEHS NIH HHS P30 ES006694 · NHLBI NIH HHS R01 HL139634 · NHLBI NIH HHS R01 HL127332 · NHLBI NIH HHS U10 HL064313
참고문헌
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