Accepted for Publication: December 18, 2013.
Published Online: February 17, 2014. doi:10.1001/jamaneurol.2013.6237.
Study concept and design: Cady, Koval, Baloh, Goate, Miller, Cruchaga, Harms.
Acquisition of data: Cady, Koval, Benitez, Jockel-Balsarotti, Allred, Ravits, Simpson, Appel, Pestronk, Cruchaga, Harms.
Analysis and interpretation of data: Cady, Koval, Benitez, Zaidman, Miller, Cruchaga, Harms.
Drafting of the manuscript: Cady, Koval, Benitez, Jockel-Balsarotti, Pestronk, Harms.
Critical revision of the manuscript for important intellectual content: Cady, Benitez, Zaidman, Allred, Baloh, Ravits, Simpson, Appel, Pestronk, Goate, Miller, Cruchaga, Harms.
Statistical analysis: Cady, Koval, Zaidman, Cruchaga.
Obtained funding: Ravits, Goate, Miller, Cruchaga, Harms.
Administrative, technical, or material support: Allred, Appel, Pestronk, Miller.
Study supervision: Baloh, Pestronk, Goate, Miller, Harms.
Conflict of Interest Disclosures: Dr Ravits receives research support from the ALS Association, Microsoft Research, and P2ALS; serves as an unpaid consultant to the Muscular Dystrophy Association; and serves as a consultant for Isis Pharmaceuticals, Inc. Dr Appel receives grant support from the Hamill foundation, not associated with the present work. Dr Pestronk receives revenue related to antibody patent licenses and speaker honoraria from Athena; owns stock in Johnson & Johnson; directs the Washington University Neuromuscular Clinical Laboratory, which performs antibody testing; and receives research support from the National Institutes of Health (NIH), Muscular Dystrophy Association, Neuromuscular Research Fund, Insmed, Knopp, Cytokinetics, Biogen Idec, ISIS, Genzyme, Glaxo SmithKline, sanofi-aventis, and Ultragenyx. Dr Goate provides consultation or expert testimony to Finnegan; receives grants from Genentech, Pfizer, and AstraZeneca for Alzheimer disease genetic research; has received honoraria from Genentech and Amgen for speaking on Alzheimer disease genetics; and receives royalties from Taconic for tau mutation patents. Dr Miller receives nonfinancial support from Regulus Therapeutics, not associated with the present work; receives grants and nonfinancial support from Isis Pharmaceuticals, not associated with the present work; and has a patent pending on miR-155 inhibition in ALS. Dr Harms has received honoraria from Genzyme for speaking on neuromuscular genetics; has provided expert testimony in medicolegal proceedings; has received grant support from Ultragenyx, not associated with the present work; and receives grant funding from the Barnes Jewish Foundation and NIH. No other disclosures were reported.
Funding/Support: This work was supported by NIH grants K08-NS075094 (Dr Harms), R01-AG044546 (Dr Cruchaga), R01-NS078398-02 (Dr Miller), and R01-NS069669 (Dr Baloh), as well as the Hope Center for Neurological Disorders. This research was conducted with Dr Cruchaga as the recipient of a New Investigator Award in Alzheimer’s disease form the American Federation for Aging Research, and Ms Cady was funded by the Genetics Epidemiology Training grant 5 T32 HL 83822-5. Dr Baloh holds a career Award for Medical Scientists from the Burroughs Wellcome Fund. This publication was made possible by grant UL1 RR024992 from the National Center for Research Resources, a component of the NIH, and NIH Roadmap for Medical Research.
Role of the Sponsor: The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Disclaimer: The contents of the article are solely the responsibility of the authors and do not necessarily represent the official view of the National Center for Research Resources or the NIH.
Additional Contributions: The authors thank the National Heart, Lung, and Blood Institute Grand Opportunity Exome Sequencing Project and its ongoing studies, which produced and provided exome variant calls for comparison: the Lung Grand Opportunity Sequencing Project (HL-102923), the Women’s Health Initiative Sequencing Project (HL-102924), the Broad Grand Opportunity Sequencing Project (HL-102925), the Seattle Grand Opportunity Sequencing Project (HL-102926), and the Heart Grand Opportunity Sequencing Project (HL-103010). DNA panels and clinical data from the National Institute of Neurological Disorders and Stroke Human Genetics Resource Center DNA and Cell Line Repository (http://ccr.coriell.org/ninds) were used in this study. The individuals who contributed samples are acknowledged in detailed descriptions of each panel: NDPT020, NDPT025, NDPT026, NDPT079, NDPT82, NDPT095, NDPT096, NDPT100, NDPT103, NDPT106, and NDPT116. DNA samples from the Washington University Neuromuscular Genetics Project and autopsy tissue from the Washington University ALS Tissue Donation Program were used in this study. Tara Skorupa, BA (Department of Psychiatry, Washington University), and Paul Cooper, BA (Department of Neurology, Washington University), performed assays; Ryan Libby, BA, and Michael Baughn, BA (Department of Neurosciences, University of California, San Diego), contributed participant recruitment and sample processing; and Sharon Halton, MSW, LCSW, and Luis Lay Jr, MD (Department of Neurology, The Methodist Hospital), contributed participant recruitment and data collection.