Meta-analysis of gene-level tests for rare variant association (original) (raw)

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Acknowledgements

The authors would like to thank M. Boehnke, X. Wen and S. Zoellner for helpful discussions. This work was supported by research grants R01HG007022 from the National Human Genome Research Institute, R01EY022005 from the National Eye Institute and R01HL117626 from the National Heart, Lung, and Blood Institute. G.M.P. was supported by award T32HL007208 from the National Heart, Lung, and Blood Institute. S.K. is supported by a Research Scholar award from Massachusetts General Hospital (MGH), the Howard Goodman Fellowship from MGH, the Donovan Family Foundation and grant R01HL107816 from the National Heart, Lung, and Blood Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung, and Blood Institute or the US National Institutes of Health. The WHI program is funded by the National Heart, Lung, and Blood Institute, US National Institutes of Health, US Department of Health and Human Services through contracts N01WH22110, N01WH24152, N01WH32100-2, N01WH32105-6, N01WH32108-9, N01WH32111-13, N01WH32115, N01WH32118-32119, N01WH32122, N01WH42107-26, N01WH42129-32 and N01WH44221. This manuscript was prepared in collaboration with investigators from the WHI and has been approved by the WHI. WHI investigators are listed at https://cleo.whi.org/researchers/SitePages/WHI%20Investigators.aspx. The full list of PROCARDIS acknowledgments is available at http://www.procardis.org/. The Ottawa Heart Genomics Study was supported by Canadian Institutes of Health Research (CIHR) grants MOP-82810, MOP-77682 and MOP-2380941 and Canada Foundation for Innovation (CFI) grant 11966. The studies for the Malmö Diet and Cancer cohort were supported by grants from the Swedish Research Council, the Swedish Heart and Lung Foundation, the Påhlsson Foundation, the Novo Nordic Foundation and European Research Council starting grant StG-282255.

Author information

Author notes

1. Dajiang J Liu, Gina M Peloso, Xiaowei Zhan and Oddgeir L Holmen: These authors contributed equally to this work.
2. Sekar Kathiresan and Gonçalo R Abecasis: These authors jointly directed this work.

Authors and Affiliations

1. Department of Biostatistics, Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, Michigan, USA
   Dajiang J Liu, Xiaowei Zhan, Matthew Zawistowski, Shuang Feng & Gonçalo R Abecasis
2. Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA
   Gina M Peloso & Sekar Kathiresan
3. Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA
   Gina M Peloso & Sekar Kathiresan
4. Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA
   Gina M Peloso & Sekar Kathiresan
5. Department of Public Health and General Practice, HUNT Research Centre, Norwegian University of Science and Technology, Levanger, Norway
   Oddgeir L Holmen & Kristian Hveem
6. St. Olav Hospital, Trondheim University Hospital, Trondheim, Norway
   Oddgeir L Holmen
7. University of Ottawa Heart Institute, Ottawa, Ontario, Canada
   Majid Nikpay & Ruth McPherson
8. Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
   Paul L Auer, Ulrike Peters & Charles Kooperberg
9. School of Public Health, University of Wisconsin–Milwaukee, Milwaukee, Wisconsin, USA
   Paul L Auer
10. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
    Anuj Goel, Martin Farrall & Hugh Watkins
11. Department of Cardiovascular Medicine, University of Oxford, Oxford, UK
    Anuj Goel, Martin Farrall, Marju Orho-Melander, Hugh Watkins & Olle Melander
12. Division of Cardiology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA
    He Zhang & Cristen J Willer
13. Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan, USA
    He Zhang & Cristen J Willer
14. Department of Epidemiology, University of Washington School of Public Health, Seattle, Washington, USA
    Ulrike Peters
15. Department of Clinical Sciences, Lund University, Malmö, Sweden
    Marju Orho-Melander & Olle Melander
16. Department of Biostatistics, University of Washington School of Public Health, Seattle, Washington, USA
    Charles Kooperberg
17. Department of Medicine, Levanger Hospital, Nord-Trøndelag Health Trust, Levanger, Norway
    Kristian Hveem
18. Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
    Sekar Kathiresan

Authors

1. Dajiang J Liu
2. Gina M Peloso
3. Xiaowei Zhan
4. Oddgeir L Holmen
5. Matthew Zawistowski
6. Shuang Feng
7. Majid Nikpay
8. Paul L Auer
9. Anuj Goel
10. He Zhang
11. Ulrike Peters
12. Martin Farrall
13. Marju Orho-Melander
14. Charles Kooperberg
15. Ruth McPherson
16. Hugh Watkins
17. Cristen J Willer
18. Kristian Hveem
19. Olle Melander
20. Sekar Kathiresan
21. Gonçalo R Abecasis

Contributions

D.J.L., S.K. and G.R.A. conceived and designed the study. D.J.L., G.M.P. and X.Z. carried out primary data analysis. D.J.L., X.Z. and S.F. wrote the software package implementing the proposed methodologies. O.L.H., M.N., P.L.A., A.G., H.Z., U.P., M.F., M.O.-M., C.K., R.M., H.W., C.J.W., K.H. and O.M. contributed phenotypes, exome array genotypes and analyses for the study. M.Z. conducted population genetics simulation analysis. D.J.L. and G.R.A. wrote the first version of the manuscript. All authors critically reviewed and approved the manuscript. S.K. and G.R.A. jointly supervised the study.

Corresponding authors

Correspondence toDajiang J Liu or Gonçalo R Abecasis.

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Competing interests

The authors declare no competing financial interests.

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Liu, D., Peloso, G., Zhan, X. et al. Meta-analysis of gene-level tests for rare variant association.Nat Genet 46, 200–204 (2014). https://doi.org/10.1038/ng.2852

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• Received: 18 March 2013
• Accepted: 20 November 2013
• Published: 15 December 2013
• Issue date: February 2014
• DOI: https://doi.org/10.1038/ng.2852