Abstract
Disaggregation and estimation of genetic effects from offspring and parents has long been of interest to statistical geneticists. Recently, technical and methodological advances have made the genome-wide and loci-specific estimation of direct offspring and parental genetic nurture effects more possible. However, unbiased estimation using these methods requires datasets where both parents and at least one child have been genotyped, which are relatively scarce. Our group has recently developed a method and accompanying software (IMPISH; Hwang et al. in PLoS Genet 16:e1009154, 2020) which is able to impute missing parental genotypes from observed data on sibships and estimate their effects on an offspring phenotype conditional on the effects of genetic transmission. However, this method is unable to disentangle maternal and paternal effects, which may differ in magnitude and direction. Here, we introduce an extension to the original IMPISH routine which takes advantage of all available nuclear families to impute parent-specific missing genotypes and obtain asymptotically unbiased estimates of genetic effects on offspring phenotypes. We apply this this method to data from related individuals in the UK Biobank, showing concordance with previous estimates of maternal genetic effects on offspring birthweight. We also conduct the first GWAS jointly estimating offspring-, maternal-, and paternal-specific genetic effects on body-mass index.
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Funding
D.M.E. is funded by an Australian National Health and Medical Research Council Senior Research Fellowship (APP1137714) and NHMRC project Grants (GNT1125200, GNT1157714, GNT1183074).
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Justin D. Tubbs, Liang-Dar Hwang, Justin Luong, David M. Evans and Pak C. Sham declare no conflicts of interest.
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This research has been conducted using the UK Biobank Resource under project ID number 28732. UK Biobank received ethical approval from the NHS National Research Ethics Service North West (11/NW/0382).
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Edited by Elizabeth Prom-Wormley.
Justin D. Tubbs and Liang-Dar Hwang are joint first authors.
David M. Evans and Pak C. Sham are joint senior authors.
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Tubbs, J.D., Hwang, LD., Luong, J. et al. Modeling Parent-Specific Genetic Nurture in Families with Missing Parental Genotypes: Application to Birthweight and BMI. Behav Genet 51, 289–300 (2021). https://doi.org/10.1007/s10519-020-10040-w
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DOI: https://doi.org/10.1007/s10519-020-10040-w