Deriving GWAS summary estimates for paternal smoking in UK biobank: a GWAS by subtraction
Abstract Objective To use genome-wide association study (GWAS) by subtraction, a method for deriving novel GWASs from existing summary statistics, to derive genome-wide summary statistics for paternal smoking. Result A GWAS by subtraction was implemented using a weighted linear model that defined th...
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BMC
2023-07-01
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| Online Access: | https://doi.org/10.1186/s13104-023-06438-4 |
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| author | Benjamin Woolf Hannah M. Sallis Marcus R. Munafò Dipender Gill |
| author_facet | Benjamin Woolf Hannah M. Sallis Marcus R. Munafò Dipender Gill |
| author_sort | Benjamin Woolf |
| collection | DOAJ |
| description | Abstract Objective To use genome-wide association study (GWAS) by subtraction, a method for deriving novel GWASs from existing summary statistics, to derive genome-wide summary statistics for paternal smoking. Result A GWAS by subtraction was implemented using a weighted linear model that defined the child-genotype paternal-phenotype association as the child-genotype child-phenotype association minus the child-genotype maternal-phenotype association. We first use the laws of inherence to derive the weighted linear model. We then implemented the linear model to create a GWAS of paternal smoking by subtracting the summary statistics from a GWAS of maternal smoking from the summary statistics of a GWAS of the index individual’s smoking. We used a Monte-Carlo simulation to validate the model and showed that this approach performed similarly in terms of bias to performing a traditional GWAS of paternal smoking. Finally, we validated the summary statistics in a Mendelian randomisation analysis by demonstrating an association of genetically predicted paternal smoking with paternal lung cancer and emphysema. |
| format | Article |
| id | doaj-art-8d5f32bb2abb41d1ad042d74f4ce3949 |
| institution | DOAJ |
| issn | 1756-0500 |
| language | English |
| publishDate | 2023-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Research Notes |
| spelling | doaj-art-8d5f32bb2abb41d1ad042d74f4ce39492025-08-20T03:11:07ZengBMCBMC Research Notes1756-05002023-07-011611710.1186/s13104-023-06438-4Deriving GWAS summary estimates for paternal smoking in UK biobank: a GWAS by subtractionBenjamin Woolf0Hannah M. Sallis1Marcus R. Munafò2Dipender Gill3School of Psychological Science, University of BristolMRC Integrative Epidemiology Unit at the University of BristolSchool of Psychological Science, University of BristolDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College LondonAbstract Objective To use genome-wide association study (GWAS) by subtraction, a method for deriving novel GWASs from existing summary statistics, to derive genome-wide summary statistics for paternal smoking. Result A GWAS by subtraction was implemented using a weighted linear model that defined the child-genotype paternal-phenotype association as the child-genotype child-phenotype association minus the child-genotype maternal-phenotype association. We first use the laws of inherence to derive the weighted linear model. We then implemented the linear model to create a GWAS of paternal smoking by subtracting the summary statistics from a GWAS of maternal smoking from the summary statistics of a GWAS of the index individual’s smoking. We used a Monte-Carlo simulation to validate the model and showed that this approach performed similarly in terms of bias to performing a traditional GWAS of paternal smoking. Finally, we validated the summary statistics in a Mendelian randomisation analysis by demonstrating an association of genetically predicted paternal smoking with paternal lung cancer and emphysema.https://doi.org/10.1186/s13104-023-06438-4GWAS-by-subtractionIntergenerational Mendelian randomisationFamily GWASGenome Wide association studies |
| spellingShingle | Benjamin Woolf Hannah M. Sallis Marcus R. Munafò Dipender Gill Deriving GWAS summary estimates for paternal smoking in UK biobank: a GWAS by subtraction BMC Research Notes GWAS-by-subtraction Intergenerational Mendelian randomisation Family GWAS Genome Wide association studies |
| title | Deriving GWAS summary estimates for paternal smoking in UK biobank: a GWAS by subtraction |
| title_full | Deriving GWAS summary estimates for paternal smoking in UK biobank: a GWAS by subtraction |
| title_fullStr | Deriving GWAS summary estimates for paternal smoking in UK biobank: a GWAS by subtraction |
| title_full_unstemmed | Deriving GWAS summary estimates for paternal smoking in UK biobank: a GWAS by subtraction |
| title_short | Deriving GWAS summary estimates for paternal smoking in UK biobank: a GWAS by subtraction |
| title_sort | deriving gwas summary estimates for paternal smoking in uk biobank a gwas by subtraction |
| topic | GWAS-by-subtraction Intergenerational Mendelian randomisation Family GWAS Genome Wide association studies |
| url | https://doi.org/10.1186/s13104-023-06438-4 |
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