Inbreeding depression caused by ROH.
a Effect of different ROH lengths on height, compared with the effect of SNP homozygosity outside of ROH. The effects of shorter (<5 Mb) and longer (>5 Mb) ROH per unit length are similar and strongly negative, whereas the effect of homozygosity outside ROH is much weaker. The pattern is similar for other traits (Supplementary Fig. ; Supplementary Data ).
b 


is more strongly associated than



in a bivariate model of height. Meta-analysed effect estimates, and 95% confidence intervals, are shown for a bivariate model of height (



). The reduction in height is more strongly associated with



than



, as predicted if the causal variants are in weak LD with the common SNPs used to calculate



(Supplementary Note ). The pattern is similar for other traits (Supplementary Fig. ; Supplementary Data ).
c FROH is a lower variance estimator of the inbreeding coefficient than
FGRM. The ratio of



is plotted against



for all traits in all cohorts. When the variation of



which is independent of



has no effect on traits,



is downwardly biased by a factor of



(Supplementary Note ). A linear maximum likelihood fit, shown in red, has a gradient consistent with unity [1.01; 95% CI 0.84–1.18], as expected when the difference between



and



is not informative about the excess homozygosity at causal variants (Supplementary Note ).
d FROH is a better predictor of rare variant homozygosity than
FGRM. The excess homozygosities of SNPs, extracted from UK Biobank imputed genotypes, were calculated at seven discrete minor allele frequencies (



), and regressed on two estimators of inbreeding in a bivariate statistical model (see Supplementary Note ). The homozygosity of common SNPs is better predicted by



, but rare variant homozygosity is better predicted by



. The results from real data (Fig. 4b, Supplementary Figs and Supplementary Data ) are consistent with those simulated here, if the causal variants are predominantly rare. All errors bars represent 95% confidence intervals