Functional variants in the LRRK2 gene confer shared effects on risk for Crohn’s disease and Parkinson’s disease-Reference-Cited by-同舟云学术

Functional variants in the LRRK2 gene confer shared effects on risk for Crohn’s disease and Parkinson’s disease

Published:2018-01-10 Issue:423 Volume:10 Page:
ISSN:1946-6234
Container-title:Science Translational Medicine
language:en
Short-container-title:Sci. Transl. Med.

Author:

Hui Ken Y.¹²,Fernandez-Hernandez Heriberto³,Hu Jianzhong³,Schaffner Adam⁴⁵^ORCID,Pankratz Nathan⁶^ORCID,Hsu Nai-Yun³^ORCID,Chuang Ling-Shiang³^ORCID,Carmi Shai⁷^ORCID,Villaverde Nicole³^ORCID,Li Xianting⁴^ORCID,Rivas Manual⁸⁹^ORCID,Levine Adam P.¹⁰^ORCID,Bao Xiuliang³^ORCID,Labrias Philippe R.³^ORCID,Haritunians Talin¹¹^ORCID,Ruane Darren¹²,Gettler Kyle¹¹³,Chen Ernie³^ORCID,Li Dalin¹¹^ORCID,Schiff Elena R.¹⁰^ORCID,Pontikos Nikolas¹⁰^ORCID,Barzilai Nir¹⁴,Brant Steven R.¹⁵¹⁶^ORCID,Bressman Susan¹⁷^ORCID,Cheifetz Adam S.¹⁸,Clark Lorraine N.¹⁹²⁰,Daly Mark J.⁸⁹²⁰²¹^ORCID,Desnick Robert J.³^ORCID,Duerr Richard H.²²²³^ORCID,Katz Seymour²⁴²⁵²⁶^ORCID,Lencz Todd²⁷^ORCID,Myers Richard H.²⁸^ORCID,Ostrer Harry²⁹^ORCID,Ozelius Laurie³³⁰^ORCID,Payami Haydeh³¹³²^ORCID,Peter Yakov³³³⁴^ORCID,Rioux John D.³⁵³⁶^ORCID,Segal Anthony W.¹⁰^ORCID,Scott William K.³⁷^ORCID,Silverberg Mark S.³⁸³⁹,Vance Jeffery M.³⁷^ORCID,Ubarretxena-Belandia Iban⁵,Foroud Tatiana⁴⁰^ORCID,Atzmon Gil¹⁴⁴¹^ORCID,Pe’er Itsik⁴²^ORCID,Ioannou Yiannis³,McGovern Dermot P. B.¹¹,Yue Zhenyu⁴,Schadt Eric E.³⁴³⁴⁴,Cho Judy H.¹³¹³⁴⁵^ORCID,Peter Inga³⁴³^ORCID

Affiliation:

1. Section of Digestive Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.

2. Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA.

3. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

4. Departments of Neurology and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

5. Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

6. Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA.

7. Braun School of Public Health and Community Medicine, The Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel.

8. Department of Medical and Population Genetics, Broad Institute, Cambridge, MA 02142, USA.

9. Analytical and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA.

10. Centre for Molecular Medicine, Division of Medicine, University College, London WC1E 6JF, UK.

11. Translational Genomics Group, F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.

12. Department of Immunology and Inflammation, Regeneron Pharmaceuticals, Tarrytown, NY 10591, USA.

13. Department of Genetics, Yale University, New Haven, CT 06520, USA.

14. Departments of Genetics and Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

15. Harvey M. and Lyn P. Meyerhoff Inflammatory Bowel Disease Center, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD 21231, USA.

16. Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21231, USA.

17. Alan and Barbara Mirken Department of Neurology, Beth Israel Medical Center, New York, NY 10003, USA.

18. Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.

19. Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA.

20. Taub Institute for Alzheimer’s Disease and the Aging Brain, Columbia University Medical Center, New York, NY 10032, USA.

21. Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.

22. Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.

23. Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA 15261, USA.

24. New York University School of Medicine, New York City, NY 10016, USA.

25. North Shore University-Long Island Jewish Medical Center, Manhasset, NY, USA.

26. St. Francis Hospital, Roslyn, NY 11576, USA.

27. Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY 11030, USA.

28. Department of Neurology, Boston University School of Medicine, Boston, MA 02114, USA.

29. Departments of Pathology and Pediatrics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

30. Deparment of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA.

31. Departments of Neurology and Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.

32. HudsonAlpha Institute for Biotechnology, Huntsville, AL 35805, USA.

33. Department of Biology, Touro College, Queens, NY 10033, USA.

34. Department of Pulmonary Medicine, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY 10033, USA.

35. Research Center, Montreal Heart Institute, Montreal, Quebec H1T1C8, Canada.

36. Faculté de Médecine, Université de Montréal, Montreal, Quebec H1T1C8, Canada.

37. Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL 33136, USA.

38. Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario M5T3L9, USA.

39. Department of Medicine, University of Toronto, Toronto, Ontario M5G1X5, Canada.

40. Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

41. Faculty of Natural Sciences, University of Haifa, Haifa 3498838, Israel.

42. Center for Computational Biology and Bioinformatics, Columbia University, New York, NY 10032, USA.

43. Institute for Genetics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

44. Sema4, a Mount Sinai venture, Stamford, CT 06902, USA.

45. Section of Gastroenterology and Hepatology, Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06520, USA.

Abstract

Crohn’s disease (CD)–associated variants in the LRRK2 gene for risk (N2081D) and for protection (N551K) mediate shared effects in CD and Parkinson’s disease.

Funder

National Science Foundation

National Institutes of Health

National Institute of Mental Health

National Institute on Aging

National Cancer Institute

National Institute of Allergy and Infectious Diseases

National Institute of General Medical Sciences

National Institute of Neurological Disorders and Stroke

National Institute of Diabetes and Digestive and Kidney Diseases

Crohn’s and Colitis Foundation of America

United States - Israel Binational Science Foundation