UMass Chan Medical School Faculty Publications

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Department of Neurology

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Article Preprint


Genetic Phenomena | Genetics | Genomics | Nervous System Diseases


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.


genetics, Project MinE, genome sequencing, ALS, amyotrophic lateral sclerosis, The Netherlands

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The copyright holder for this preprint (which was not peer-reviewed) is the author/funder.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.

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bioRxiv 152553; doi: Link to preprint on bioRxiv service.


Full author list omitted for brevity. For the full list of authors, see article.

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Creative Commons Attribution-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-No Derivative Works 4.0 License.