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Human loss-of-function variants suggest that partial LRRK2 inhibition is a safe therapeutic strategy for Parkinson’s disease
View ORCID ProfileNicola Whiffin, Irina M. Armean, Aaron Kleinman, Jamie L. Marshall, View ORCID ProfileEric V. Minikel, View ORCID ProfileKonrad J. Karczewski, View ORCID ProfileBeryl B. Cummings, View ORCID ProfileLaurent Francioli, Kristen Laricchia, Qingbo Wang, Anna Guan, View ORCID ProfileBabak Alipanahi, Peter Morrison, Marco A.S. Baptista, Kalpana M. Merchant, Genome Aggregation Database Production Team, Genome Aggregation Database Consortium, View ORCID ProfileJames S. Ware, Aki S. Havulinna, Bozenna Iliadou, Jung-Jin Lee, Girish N. Nadkarni, Cole Whiteman, the 23andMe Research Team, Mark Daly, View ORCID ProfileTõnu Esko, View ORCID ProfileChristina Hultman, View ORCID ProfileRuth J.F. Loos, View ORCID ProfileLili Milani, Aarno Palotie, Carlos Pato, Michele Pato, View ORCID ProfileDanish Saleheen, Patrick F. Sullivan, Jessica Alföldi, Paul Cannon, Daniel G. MacArthur
doi: https://doi.org/10.1101/561472
Nicola Whiffin
1National Heart & Lung Institute and MRC London Institute of Medical Sciences, Imperial College London, London UK
2Cardiovascular Research Centre, Royal Brompton & Harefield Hospitals NHS Trust, London UK
3Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA
Irina M. Armean
3Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA
4Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
Aaron Kleinman
523andMe, Inc.
Jamie L. Marshall
3Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA
Eric V. Minikel
3Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA
Konrad J. Karczewski
3Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA
4Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
Beryl B. Cummings
3Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA
4Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
6Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA, 02115, USA
Laurent Francioli
3Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA
4Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
Kristen Laricchia
3Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA
4Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
Qingbo Wang
3Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA
4Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
7Program in Bioinformatics and Integrative Genomics, Harvard Medical School, Boston, MA 02115, USA
Anna Guan
523andMe, Inc.
Babak Alipanahi
523andMe, Inc.
Peter Morrison
523andMe, Inc.
Marco A.S. Baptista
8Michael J. Fox Foundation
Kalpana M. Merchant
8Michael J. Fox Foundation
James S. Ware
1National Heart & Lung Institute and MRC London Institute of Medical Sciences, Imperial College London, London UK
2Cardiovascular Research Centre, Royal Brompton & Harefield Hospitals NHS Trust, London UK
3Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA
Aki S. Havulinna
9Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland
10National Institute for Health and Welfare, 00271, Helsinki, Finland
Bozenna Iliadou
11Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
Jung-Jin Lee
12Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
Girish N. Nadkarni
13The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY
14Department of Medicine, Icahn School of Medicine at Mount Sinai
Cole Whiteman
15Department of Psychiatry and the Behavioral Sciences, State University of New York, Downstate Medical Center, New York, New York
Mark Daly
3Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA
4Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
16Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA
Tõnu Esko
3Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA
17Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia
Christina Hultman
11Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
14Department of Medicine, Icahn School of Medicine at Mount Sinai
Ruth J.F. Loos
13The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY
18The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY
Lili Milani
17Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia
Aarno Palotie
4Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
9Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland
16Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA
Carlos Pato
15Department of Psychiatry and the Behavioral Sciences, State University of New York, Downstate Medical Center, New York, New York
Michele Pato
15Department of Psychiatry and the Behavioral Sciences, State University of New York, Downstate Medical Center, New York, New York
Danish Saleheen
12Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
19Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
20Center for Non-Communicable Diseases, Karachi, Pakistan
Patrick F. Sullivan
11Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
21Departments of Genetics and Psychiatry, University of North Carolina, Chapel Hill, NC, USA
Jessica Alföldi
3Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA
4Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
Paul Cannon
523andMe, Inc.
Daniel G. MacArthur
3Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA
4Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
Posted February 27, 2019.
Human loss-of-function variants suggest that partial LRRK2 inhibition is a safe therapeutic strategy for Parkinson’s disease
Nicola Whiffin, Irina M. Armean, Aaron Kleinman, Jamie L. Marshall, Eric V. Minikel, Konrad J. Karczewski, Beryl B. Cummings, Laurent Francioli, Kristen Laricchia, Qingbo Wang, Anna Guan, Babak Alipanahi, Peter Morrison, Marco A.S. Baptista, Kalpana M. Merchant, Genome Aggregation Database Production Team, Genome Aggregation Database Consortium, James S. Ware, Aki S. Havulinna, Bozenna Iliadou, Jung-Jin Lee, Girish N. Nadkarni, Cole Whiteman, the 23andMe Research Team, Mark Daly, Tõnu Esko, Christina Hultman, Ruth J.F. Loos, Lili Milani, Aarno Palotie, Carlos Pato, Michele Pato, Danish Saleheen, Patrick F. Sullivan, Jessica Alföldi, Paul Cannon, Daniel G. MacArthur
bioRxiv 561472; doi: https://doi.org/10.1101/561472
Human loss-of-function variants suggest that partial LRRK2 inhibition is a safe therapeutic strategy for Parkinson’s disease
Nicola Whiffin, Irina M. Armean, Aaron Kleinman, Jamie L. Marshall, Eric V. Minikel, Konrad J. Karczewski, Beryl B. Cummings, Laurent Francioli, Kristen Laricchia, Qingbo Wang, Anna Guan, Babak Alipanahi, Peter Morrison, Marco A.S. Baptista, Kalpana M. Merchant, Genome Aggregation Database Production Team, Genome Aggregation Database Consortium, James S. Ware, Aki S. Havulinna, Bozenna Iliadou, Jung-Jin Lee, Girish N. Nadkarni, Cole Whiteman, the 23andMe Research Team, Mark Daly, Tõnu Esko, Christina Hultman, Ruth J.F. Loos, Lili Milani, Aarno Palotie, Carlos Pato, Michele Pato, Danish Saleheen, Patrick F. Sullivan, Jessica Alföldi, Paul Cannon, Daniel G. MacArthur
bioRxiv 561472; doi: https://doi.org/10.1101/561472
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