Rare variant association analysis in case-parents studies by allowing for missing parental genotypes
Abstract Background The development of next-generation sequencing technologies has facilitated the identification of rare variants. Family-based design is commonly used to effectively control for population admixture and substructure, which is more prominent for rare variants. Case-parents studies,...
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| Format: | Article |
| Language: | English |
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BMC
2018-01-01
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| Series: | BMC Genetics |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12863-018-0597-8 |
| _version_ | 1828528193401782272 |
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| author | Yumei Li Yang Xiang Chao Xu Hui Shen Hongwen Deng |
| author_facet | Yumei Li Yang Xiang Chao Xu Hui Shen Hongwen Deng |
| author_sort | Yumei Li |
| collection | DOAJ |
| description | Abstract Background The development of next-generation sequencing technologies has facilitated the identification of rare variants. Family-based design is commonly used to effectively control for population admixture and substructure, which is more prominent for rare variants. Case-parents studies, as typical strategies in family-based design, are widely used in rare variant-disease association analysis. Current methods in case-parents studies are based on complete case-parents data; however, parental genotypes may be missing in case-parents trios, and removing these data may lead to a loss in statistical power. The present study focuses on testing for rare variant-disease association in case-parents study by allowing for missing parental genotypes. Results In this report, we extended the collapsing method for rare variant association analysis in case-parents studies to allow for missing parental genotypes, and investigated the performance of two methods by using the difference of genotypes between affected offspring and their corresponding “complements” in case-parent trios and TDT framework. Using simulations, we showed that, compared with the methods just only using complete case-parents data, the proposed strategy allowing for missing parental genotypes, or even adding unrelated affected individuals, can greatly improve the statistical power and meanwhile is not affected by population stratification. Conclusions We conclude that adding case-parents data with missing parental genotypes to complete case-parents data set can greatly improve the power of our strategy for rare variant-disease association. |
| first_indexed | 2024-12-11T21:48:52Z |
| format | Article |
| id | doaj.art-779486edd3c54718afb53bfc18d93035 |
| institution | Directory Open Access Journal |
| issn | 1471-2156 |
| language | English |
| last_indexed | 2024-12-11T21:48:52Z |
| publishDate | 2018-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Genetics |
| spelling | doaj.art-779486edd3c54718afb53bfc18d930352022-12-22T00:49:32ZengBMCBMC Genetics1471-21562018-01-011911810.1186/s12863-018-0597-8Rare variant association analysis in case-parents studies by allowing for missing parental genotypesYumei Li0Yang Xiang1Chao Xu2Hui Shen3Hongwen Deng4School of Mathematics and Computational Science, Huaihua UniversitySchool of Mathematics and Computational Science, Huaihua UniversityCenter for Bioinformatics and Genomics, Department of Global Biostatistics and Data Science, Tulane UniversityCenter for Bioinformatics and Genomics, Department of Global Biostatistics and Data Science, Tulane UniversityCenter for Bioinformatics and Genomics, Department of Global Biostatistics and Data Science, Tulane UniversityAbstract Background The development of next-generation sequencing technologies has facilitated the identification of rare variants. Family-based design is commonly used to effectively control for population admixture and substructure, which is more prominent for rare variants. Case-parents studies, as typical strategies in family-based design, are widely used in rare variant-disease association analysis. Current methods in case-parents studies are based on complete case-parents data; however, parental genotypes may be missing in case-parents trios, and removing these data may lead to a loss in statistical power. The present study focuses on testing for rare variant-disease association in case-parents study by allowing for missing parental genotypes. Results In this report, we extended the collapsing method for rare variant association analysis in case-parents studies to allow for missing parental genotypes, and investigated the performance of two methods by using the difference of genotypes between affected offspring and their corresponding “complements” in case-parent trios and TDT framework. Using simulations, we showed that, compared with the methods just only using complete case-parents data, the proposed strategy allowing for missing parental genotypes, or even adding unrelated affected individuals, can greatly improve the statistical power and meanwhile is not affected by population stratification. Conclusions We conclude that adding case-parents data with missing parental genotypes to complete case-parents data set can greatly improve the power of our strategy for rare variant-disease association.http://link.springer.com/article/10.1186/s12863-018-0597-8Rare-variant association analysisCase-parent triosCollapsing method |
| spellingShingle | Yumei Li Yang Xiang Chao Xu Hui Shen Hongwen Deng Rare variant association analysis in case-parents studies by allowing for missing parental genotypes BMC Genetics Rare-variant association analysis Case-parent trios Collapsing method |
| title | Rare variant association analysis in case-parents studies by allowing for missing parental genotypes |
| title_full | Rare variant association analysis in case-parents studies by allowing for missing parental genotypes |
| title_fullStr | Rare variant association analysis in case-parents studies by allowing for missing parental genotypes |
| title_full_unstemmed | Rare variant association analysis in case-parents studies by allowing for missing parental genotypes |
| title_short | Rare variant association analysis in case-parents studies by allowing for missing parental genotypes |
| title_sort | rare variant association analysis in case parents studies by allowing for missing parental genotypes |
| topic | Rare-variant association analysis Case-parent trios Collapsing method |
| url | http://link.springer.com/article/10.1186/s12863-018-0597-8 |
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