Relatedness disequilibrium regression estimates heritability without environmental bias

Abstract

Heritability measures the proportion of trait variation that is due to genetic inheritance. Measurement of heritability is important in the nature-versus-nurture debate. However, existing estimates of heritability may be biased by environmental effects. Here, we introduce relatedness disequilibrium regression (RDR), a novel method for estimating heritability. RDR avoids most sources of environmental bias by exploiting variation in relatedness due to random Mendelian segregation. We used a sample of 54,888 Icelanders who had both parents genotyped to estimate the heritability of 14 traits, including height (55.4%, s.e. 4.4%) and educational attainment (17.0%, s.e. 9.4%). Our results suggest that some other estimates of heritability may be inflated by environmental effects.

Figure 1. Relatedness disequilibrium

For all pairs of individuals i,j from 20,000 Icelanders with both parents genotyped, the relatedness of i and j, [R]_i,j, is compared to the relatedness of the parents of i and the parents of j, [R_par]_ij. The number of pairs in each hexagonal bin is indicated by shading. Relationships determined by the deCODE Genealogy database are indicated: GP-GC, grandparent-grandchild; P-O, parent-offspring; and sibling. The solid diagonal line indicates the expectation of [R]_ij, which is [R_par]_ij/2, except for pairs where one is a direct ancestor of the other (Supplementary Note). The dashed diagonal line indicates the regression line (excluding parent-offspring and grandparent-grandchild pairs), with intercept -1x10^-4, gradient 0.493, and variance explained 84%. The small deviation of the regression line from the theoretical expectation is likely due to some IBD segments shared between parents being broken up by recombination, resulting in a small fraction of segments in the offspring being too small to detect. Relatedness disequilibrium is the variation in [R]_ij around [R_par]_ij/2. Relatedness disequilibrium is due to independent, random segregations in the parents, except for pairs where one is the direct ancestor of the other.

Fig. 2. Comparison of heritability estimates from different methods.

Horizontal intervals show +/-1.96 standard errors for the estimates on the x-axis, and vertical intervals show +/-1.96 standard errors for the estimates on the y-axis. See Table 2 for numerical values. A) Comparison of RDR to ‘Kinship F.E.’. B) Comparison of RDR-SNP to RELT-SNP. C) Comparison of RDR to Sib-Regression estimates. Intervals for the RDR estimates are not shown to better display Sib-Regression intervals. D) Comparison to published twin studies estimates from the Swedish Twin Registry, apart from for education, which is from a meta-analysis of Scandinavian twin studies (Supplementary Table 6). Trait abbreviations: BMI, body mass index; AFCW, age at first child in women; AFCM, age at first child in men; education, educational attainment (years); cholesterol, total cholesterol; HDL, high density lipoprotein; glucose, fasting glucose; MCH, mean cell haemoglobin; MCHC, mean cell heamoglobin concentration; MCV, mean cell volume.