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A genome-wide cross-trait analysis from UK Biobank highlights the shared genetic architecture of asthma and allergic diseases

Nature Genetics volume 50, pages 857–864 (2018)Cite this article

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An Author Correction to this article was published on 02 November 2018

Abstract

Clinical and epidemiological data suggest that asthma and allergic diseases are associated and may share a common genetic etiology. We analyzed genome-wide SNP data for asthma and allergic diseases in 33,593 cases and 76,768 controls of European ancestry from UK Biobank. Two publicly available independent genome-wide association studies 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 understanding of the molecular mechanisms underlying co-morbid asthma and allergic diseases.

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Fig. 1: Partitioned genetic correlation between asthma and allergic diseases in UK Biobank.
Fig. 2: Circus Manhattan plot of cross-trait meta-analysis.
Fig. 3: GTEx TSEA.

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Acknowledgements

This research has been conducted using the UK Biobank Resource under application number 16549. We would like to thank the participants and researchers from UK Biobank who significantly contributed or collected data. We thank the GABRIEL consortium and the EAGLE consortium for providing GWAS summary statistic data. We also thank W. Cookson and M. Moffatt their clinical advice, and D. Chasman, V. Anttila, S. Gazal, H. Shi, Y. Feng and M. Chen for their statistical advice. This study was supported by grants R01HL060710 (D.C.C.), R56HL134356 (D.C.C.), R01HL114769 (Q.L.), AAF15-0097 (Q.L.) and R00MH101367 (P.H.L.) from the National Heart, Lung, and Blood Institute (NHLBI), the National Institutes of Health, the American Asthma Foundation and the National Institute of Mental Health.

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Authors and Affiliations

  1. Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA

    Zhaozhong Zhu, Wonil Chung, Po-Ru Loh & Liming Liang

  2. Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA

    Zhaozhong Zhu & David C. Christiani

  3. Center for Genomic Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA

    Zhaozhong Zhu & Phil H. Lee

  4. Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA

    Phil H. Lee, Mark D. Chaffin & Po-Ru Loh

  5. Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA

    Phil H. Lee

  6. Program in Molecular and Integrative Physiological Sciences, Departments of Environmental Health and Genetics & Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA

    Quan Lu

  7. Pulmonary and Critical Care Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA

    David C. Christiani

  8. Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA

    Liming Liang

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Contributions

Z.Z., L.L., P.H.L., Q.L. and D.C.C. designed the study. Z.Z., M.D.C., W.C. and P.-R.L. performed the statistical analysis. Z.Z., M.D.C., L.L., W.C. and Q.L. wrote the manuscript. All authors helped interpret the data, reviewed and edited the final paper, and approved the submission.

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Correspondence to Liming Liang.

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Zhu, Z., Lee, P.H., Chaffin, M.D. et al. A genome-wide cross-trait analysis from UK Biobank highlights the shared genetic architecture of asthma and allergic diseases. Nat Genet 50, 857–864 (2018). https://doi.org/10.1038/s41588-018-0121-0

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