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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Main Authors: Benjamin Woolf, Hannah M. Sallis, Marcus R. Munafò, Dipender Gill
Format: Article
Language:English
Published: BMC 2023-07-01
Series:BMC Research Notes
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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.
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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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