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      ESPRESSO: taking into account assessment errors on outcome and exposures in power analysis for association studies

      research-article
      1 , * , 2 , 1
      Bioinformatics
      Oxford University Press

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          Abstract

          Motivation: Very large studies are required to provide sufficiently big sample sizes for adequately powered association analyses. This can be an expensive undertaking and it is important that an accurate sample size is identified. For more realistic sample size calculation and power analysis, the impact of unmeasured aetiological determinants and the quality of measurement of both outcome and explanatory variables should be taken into account. Conventional methods to analyse power use closed-form solutions that are not flexible enough to cater for all of these elements easily. They often result in a potentially substantial overestimation of the actual power.

          Results: In this article, we describe the Estimating Sample-size and Power in R by Exploring Simulated Study Outcomes tool that allows assessment errors in power calculation under various biomedical scenarios to be incorporated. We also report a real world analysis where we used this tool to answer an important strategic question for an existing cohort.

          Availability and implementation: The software is available for online calculation and downloads at http://espresso-research.org. The code is freely available at https://github.com/ESPRESSO-research.

          Contact: louqman@ 123456gmail.com

          Supplementary information: Supplementary data are available at Bioinformatics online.

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          Most cited references10

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          The future of genetic studies of complex human diseases.

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            Genome-wide association study of copy number variation in 16,000 cases of eight common diseases and 3,000 shared controls

            Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to play an important role in genetic susceptibility to common disease. To address this we undertook a large direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed ~19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated ~50% of all common CNVs larger than 500bp. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell-lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease, IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis, and type 1 diabetes, and TSPAN8 for type 2 diabetes, though in each case the locus had previously been identified in SNP-based studies, reflecting our observation that the majority of common CNVs which are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs which can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.
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              Association studies for finding cancer-susceptibility genetic variants.

              Cancer is the result of complex interactions between inherited and environmental factors. Known genes account for a small proportion of the heritability of cancer, and it is likely that many genes with modest effects are yet to be found. Genetic-association studies have been widely used in the search for such genes, but success has been limited so far. Increased knowledge of the function of genes and the architecture of human genetic variation combined with new genotyping technologies herald a new era of gene mapping by association.
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                Author and article information

                Journal
                Bioinformatics
                Bioinformatics
                bioinformatics
                bioinfo
                Bioinformatics
                Oxford University Press
                1367-4803
                1367-4811
                15 August 2015
                22 April 2015
                22 April 2015
                : 31
                : 16
                : 2691-2696
                Affiliations
                1School of Social and Community Medicine, University of Bristol, UK and
                2School of Computing Science, Newcastle University, UK
                Author notes
                *To whom correspondence should be addressed.

                Associate Editor: Alfonso Valencia

                Article
                btv219
                10.1093/bioinformatics/btv219
                4528636
                25908791
                2fbd8cd8-f9f2-43ac-93d0-44b7a616eaac
                © The Author 2015. Published by Oxford University Press.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 18 August 2014
                : 08 March 2015
                : 19 April 2015
                Page count
                Pages: 6
                Categories
                Original Papers
                Genetics and Population Analysis

                Bioinformatics & Computational biology
                Bioinformatics & Computational biology

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