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Practical Experience of the Application of a Weighted Burden Test to Whole Exome Sequence Data for Obesity and Schizophrenia
For biological and statistical reasons it makes sense to combine information from variants at the level of the gene. One may wish to give more weight to variants which are rare and those that are more likely to affect function. A combined weighting scheme, implemented in the SCOREASSOC program, was...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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John Wiley and Sons Inc.
2015
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4833177/ https://www.ncbi.nlm.nih.gov/pubmed/26474449 http://dx.doi.org/10.1111/ahg.12135 |
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author | Curtis, David |
author_facet | Curtis, David |
author_sort | Curtis, David |
collection | PubMed |
description | For biological and statistical reasons it makes sense to combine information from variants at the level of the gene. One may wish to give more weight to variants which are rare and those that are more likely to affect function. A combined weighting scheme, implemented in the SCOREASSOC program, was applied to whole exome sequence data for 1392 subjects with schizophrenia and 982 with obesity from the UK10K project. Results conformed fairly well with null hypothesis expectations and no individual gene was strongly implicated. However, a number of the higher ranked genes appear plausible candidates as being involved in one or other phenotype and may warrant further investigation. These include MC4R, NLGN2, CRP, DONSON, GTF3A, IL36B, ADCYAP1R1, ARSA, DLG1, SIK2, SLAIN1, UBE2Q2, ZNF507, CRHR1, MUSK, NSF, SNORD115, GDF3 and HIBADH. Some individual variants in these genes have different frequencies between cohorts and could be genotyped in additional subjects. For other genes, there is a general excess of variants at many different sites so attempts at replication would be more difficult. Overall, the weighted burden test provides a convenient method for using sequence data to highlight genes of interest. |
format | Online Article Text |
id | pubmed-4833177 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-48331772016-06-24 Practical Experience of the Application of a Weighted Burden Test to Whole Exome Sequence Data for Obesity and Schizophrenia Curtis, David Ann Hum Genet Original Articles For biological and statistical reasons it makes sense to combine information from variants at the level of the gene. One may wish to give more weight to variants which are rare and those that are more likely to affect function. A combined weighting scheme, implemented in the SCOREASSOC program, was applied to whole exome sequence data for 1392 subjects with schizophrenia and 982 with obesity from the UK10K project. Results conformed fairly well with null hypothesis expectations and no individual gene was strongly implicated. However, a number of the higher ranked genes appear plausible candidates as being involved in one or other phenotype and may warrant further investigation. These include MC4R, NLGN2, CRP, DONSON, GTF3A, IL36B, ADCYAP1R1, ARSA, DLG1, SIK2, SLAIN1, UBE2Q2, ZNF507, CRHR1, MUSK, NSF, SNORD115, GDF3 and HIBADH. Some individual variants in these genes have different frequencies between cohorts and could be genotyped in additional subjects. For other genes, there is a general excess of variants at many different sites so attempts at replication would be more difficult. Overall, the weighted burden test provides a convenient method for using sequence data to highlight genes of interest. John Wiley and Sons Inc. 2015-10-16 2016-01 /pmc/articles/PMC4833177/ /pubmed/26474449 http://dx.doi.org/10.1111/ahg.12135 Text en © 2015 The Authors. Annals of Human Genetics published by University College London (UCL) and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Curtis, David Practical Experience of the Application of a Weighted Burden Test to Whole Exome Sequence Data for Obesity and Schizophrenia |
title | Practical Experience of the Application of a Weighted Burden Test to Whole Exome Sequence Data for Obesity and Schizophrenia |
title_full | Practical Experience of the Application of a Weighted Burden Test to Whole Exome Sequence Data for Obesity and Schizophrenia |
title_fullStr | Practical Experience of the Application of a Weighted Burden Test to Whole Exome Sequence Data for Obesity and Schizophrenia |
title_full_unstemmed | Practical Experience of the Application of a Weighted Burden Test to Whole Exome Sequence Data for Obesity and Schizophrenia |
title_short | Practical Experience of the Application of a Weighted Burden Test to Whole Exome Sequence Data for Obesity and Schizophrenia |
title_sort | practical experience of the application of a weighted burden test to whole exome sequence data for obesity and schizophrenia |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4833177/ https://www.ncbi.nlm.nih.gov/pubmed/26474449 http://dx.doi.org/10.1111/ahg.12135 |
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