University of Massachusetts Medical School Faculty Publications
UMMS Affiliation
Department of Neurology
Publication Date
2017-06-20
Document Type
Article Preprint
Disciplines
Genetic Phenomena | Genetics | Genomics | Nervous System Diseases
Abstract
The most recent genome-wide association study in amyotrophic lateral sclerosis (ALS) demonstrates a disproportionate contribution from low-frequency variants to genetic susceptibility of disease. We have therefore begun Project MinE, an international collaboration that seeks to analyse whole-genome sequence data of at least 15,000 ALS patients and 7,500 controls. Here, we report on the design of Project MinE and pilot analyses of newly whole-genome sequenced 1,264 ALS patients and 611 controls drawn from the Netherlands. As has become characteristic of sequencing studies, we find an abundance of rare genetic variation (minor allele frequency < 0.1%), the vast majority of which is absent in public data sets. Principal component analysis reveals local geographical clustering of these variants within The Netherlands. We use the whole-genome sequence data to explore the implications of poor geographical matching of cases and controls in a sequence-based disease study and to investigate how ancestry-matched, externally sequenced controls can induce false positive associations. Also, we have publicly released genome-wide minor allele counts in cases and controls, as well as results from genic burden tests.
Keywords
genetics, Project MinE, genome sequencing, ALS, amyotrophic lateral sclerosis, The Netherlands
Rights and Permissions
The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC-BY-ND 4.0 International license.
DOI of Published Version
10.1101/152553
Source
bioRxiv 152553; doi: https://doi.org/10.1101/152553. Link to preprint on bioRxiv service.
Journal/Book/Conference Title
bioRxiv
Repository Citation
Project MinE Consortium, Van Rheenen W, Kenna KP, Landers JE, Veldink JH. (2017). Project MinE: study design and pilot analyses of a large-scale whole-genome sequencing study in amyotrophic lateral sclerosis. University of Massachusetts Medical School Faculty Publications. https://doi.org/10.1101/152553. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/1533
Creative Commons License
This work is licensed under a Creative Commons Attribution-No Derivative Works 4.0 License.
Included in
Genetic Phenomena Commons, Genetics Commons, Genomics Commons, Nervous System Diseases Commons
Comments
Full author list omitted for brevity. For the full list of authors, see article.