PT - JOURNAL ARTICLE AU - Zhaozhong Zhu AU - Xi Zhu AU - Cong-Lin Liu AU - Huwenbo Shi AU - Sipeng Shen AU - Yunqi Yang AU - Kohei Hasegawa AU - Carlos A. Camargo AU - Liming Liang TI - Shared Genetics of Asthma and Mental Health Disorders: A Large-Scale Genome-Wide Cross-Trait Analysis AID - 10.1183/13993003.01507-2019 DP - 2019 Jan 01 TA - European Respiratory Journal PG - 1901507 4099 - http://erj.ersjournals.com/content/early/2019/10/16/13993003.01507-2019.short 4100 - http://erj.ersjournals.com/content/early/2019/10/16/13993003.01507-2019.full AB - Epidemiological studies demonstrate an association between asthma and mental health disorders, although little is known about the shared genetics and causality of this association. Thus, we aim to investigate shared genetic and the causal link between asthma and mental health disorders.We conducted a large-scale genome-wide cross-trait association study to investigate genetic overlap between asthma from UK Biobank and 8 mental health disorders from Psychiatric Genomics Consortium, including: attention deficit hyperactivity disorder (ADHD), anxiety disorder (ANX), autism spectrum disorder, bipolar disorder, eating disorder, major depressive disorder (MDD), posttraumatic stress disorder, and schizophrenia, with a sample size of 7556 to 446 032.In the single trait genome-wide association analysis, we replicated 130 and discovered 31 novel independent loci that are associated with asthma. We identified that ADHD, ANX and MDD have strong genetic correlation with asthma at the genome-wide level. Cross-trait meta-analysis identified 7 loci jointly associated with asthma and ADHD, 1 loci with asthma and ANX and 10 loci with asthma and MDD. Functional analysis revealed that the identified variants regulated gene expression in major tissues belonging to exocrine/endocrine, digestive, respiratory and hemic/immune system. Mendelian randomisation analyses suggested that ADHD and MDD (including 6.7% samples overlap with asthma) might increase the risk of asthma.This large-scale genome-wide cross-trait analysis identified shared genetics and potential causal links between asthma and three mental health disorders (ADHD, ANX, and MDD). Such shared genetics implicate potential new biological functions that are in common among them.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Zhu has nothing to disclose.Conflict of interest: Dr. Zhu has nothing to disclose.Conflict of interest: Dr. Liu has nothing to disclose.Conflict of interest: Dr. Shi has nothing to disclose.Conflict of interest: Dr. Shen has nothing to disclose.Conflict of interest: Dr. Yang has nothing to disclose.Conflict of interest: Dr. Hasegawa has nothing to disclose.Conflict of interest: Dr. Camargo has nothing to disclose.Conflict of interest: Dr. Liang has nothing to disclose.