Highlights d Three groups of highly genetically-related disorders among 8 psychiatric disorders d Identified 109 pleiotropic loci affecting more than one disorder d Pleiotropic genes show heightened expression beginning in 2 nd prenatal trimester d Pleiotropic genes play prominent roles in neurodevelopmental processes Authors Cross-Disorder Group of the Psychiatric Genomics Consortium

Key messagesd This large-scale cross-trait GWAS provides strong evidence for shared genetic components between obesityrelated metabolic traits and asthma subtypes.d The strongest positive genetic correlation was observed between obesity and later-onset asthma.d Mendelian randomization analysis provided strong evidence in support of BMI causally increasing the risk of asthma.

Clinical and epidemiological data suggest that asthma and allergic diseases are associated and may share a common genetic etiology. We analyzed genome-wide single-nucleotide polymorphism (SNP) data for asthma and allergic diseases in 33,593 cases and 76,768 controls of European ancestry from the UK Biobank. Two publicly available independent genome wide association studies (GWAS) were used for replication. We have found a strong genome-wide genetic correlation between asthma and allergic diseases (rg = 0.75, P = 6.84×10−62). Cross trait analysis identified 38 genome-wide significant loci, including 7 novel shared loci. Computational analysis showed that shared genetic loci are enriched in immune/inflammatory systems and tissues with epithelium cells. Our work identifies common genetic architectures shared between asthma and allergy and will help to advance our understanding of the molecular mechanisms underlying co-morbid asthma and allergic diseases.

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