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Quantifying the effects of inbreeding is critical to characterizing the genetic architecture of complex traits. This study highlights through theory and simulations the strengths and shortcomings of three SNP-based inbreeding measures commonly used to estimate inbreeding depression (ID). We demonstrate that heterogeneity in linkage disequilibrium (LD) between causal variants and SNPs biases ID estimates, and we develop an approach to correct this bias using LD and minor allele frequency stratified inference (LDMS). We quantified ID in 25 traits measured in [Formula: see text] participants of the UK Biobank, using LDMS, and confirmed previously published ID for 4 traits. We find unique evidence of ID for handgrip strength, waist/hip ratio, and visual and auditory acuity (ID between -2.3 and -5.2 phenotypic SDs for complete inbreeding; [Formula: see text]). Our results illustrate that a careful choice of the measure of inbreeding combined with LDMS stratification improves both detection and quantification of ID using SNP data.

Original publication




Journal article


Proceedings of the National Academy of Sciences of the United States of America

Publication Date





8602 - 8607


Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia;


Humans, Consanguinity, Quantitative Trait, Heritable, Linkage Disequilibrium, Polymorphism, Single Nucleotide, Models, Genetic, Databases, Nucleic Acid, Female, Male