Detection and quantification of inbreeding depression for complex traits from SNP data [Genetics]
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 ∼140,000 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;
P<0.001). 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.
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