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Abstract
Estimation of direct and indirect (i.e. parental and/or sibling) genetic effects on phenotypes is becoming increasingly important. We compare several multivariate methods that utilize summary results statistics from genome-wide association studies to determine how well they estimate direct and indirect genetic effects. Using data from the UK Biobank, we contrast point estimates and standard errors at individual loci compared to those obtained using individual level data. We show that Genomic structural equation modelling (SEM) outperforms the other methods in accurately estimating conditional genetic effects and their standard errors. We apply Genomic SEM to fertility data in the UK Biobank and partition the genetic effect into female and male fertility and a sibling specific effect. We identify a novel locus for fertility and genetic correlations between fertility and educational attainment, risk taking behaviour, autism and subjective well-being. We recommend Genomic SEM be used to partition genetic effects into direct and indirect components when using summary results from genome-wide association studies.
22 Keywords
Adult
Autistic Disorder
Biological Specimen Banks
Educational Status
Female
Fertility
Genetic Association Studies
Genetic Loci
Genome, Human
Genome-Wide Association Study
Genomics
Genotype
Humans
Infant
Inheritance Patterns
Latent Class Analysis
Male
Models, Genetic
Phenotype
Risk-Taking
Siblings
United Kingdom
4 Authors
Nicole M. Warrington
Liang-Dar Hwang
Michel G. Nivard
David M. Evans
Enabling scientific discoveries that improve human health