Project MinE: study design and pilot analyses of a large-scale whole-genome sequencing study in amyotrophic lateral sclerosis [preprint]
Full author list omitted for brevity. For the full list of authors, see article. ; 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 Net... Mehr ...
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Dokumenttyp: | Preprint |
Erscheinungsdatum: | 2022 |
Schlagwörter: | genetics / Project MinE / genome sequencing / ALS / amyotrophic lateral sclerosis / The Netherlands / Genetic Phenomena / Genomics / Nervous System Diseases |
Sprache: | Englisch |
Permalink: | https://search.fid-benelux.de/Record/base-29197814 |
Datenquelle: | BASE; Originalkatalog |
Powered By: | BASE |
Link(s) : | https://doi.org/10.1101/152553 |
Full author list omitted for brevity. For the full list of authors, see article. ; 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.