Meta-analysis of the heritability of human traits based on fifty years of twin studies

Abstract

Despite a century of research on complex traits in humans, the relative importance and specific nature of the influences of genes and environment on human traits remain controversial. We report a meta-analysis of twin correlations and reported variance components for 17,804 traits from 2,748 publications including 14,558,903 partly dependent twin pairs, virtually all published twin studies of complex traits. Estimates of heritability cluster strongly within functional domains, and across all traits the reported heritability is 49%. For a majority (69%) of traits, the observed twin correlations are consistent with a simple and parsimonious model where twin resemblance is solely due to additive genetic variation. The data are inconsistent with substantial influences from shared environment or non-additive genetic variation. This study provides the most comprehensive analysis of the causes of individual differences in human traits thus far and will guide future gene-mapping efforts. All the results can be visualized using the MaTCH webtool.

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Figure 1: Distribution of the investigated traits in virtually all twin studies published between 1958 and 2012.
Figure 2: Twin correlations and heritabilities for all human traits studied.
Figure 3: Twin correlations for the top 20 most investigated specific traits by age and sex.

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Acknowledgements

We would like to thank M. Frantsen, M.P. Roeling, R. Lee and D.M. DeCristo for their contribution to collecting the full texts of selected twin studies and data entry. This work was funded by the Netherlands Organization for Scientific Research (NWO VICI 453-14-005, NWO Complexity 645-000-003), by the Australian Research Council (DP130102666) and by the Australian National Health and Medical Research Council (APP613601).

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Contributions

D.P., B.B., P.F.S. and P.M.V. performed the analyses. D.P. conceived the study. D.P., T.J.C.P. and P.M.V. designed the study. T.J.C.P. and D.P. collected and entered the data. D.P. and P.F.S. categorized traits according to standard classifications. A.v.B. and C.A.d.L. checked data entries, and checked and wrote statistical scripts. A.v.B. designed and programmed the webtool. D.P., T.J.C.P. and P.M.V. wrote the manuscript. All authors discussed the results and commented on the manuscript.

Corresponding author

Correspondence to Danielle Posthuma.

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Competing interests

The authors declare no competing financial interests.

Integrated supplementary information

Supplementary Figure 1 Authorship co-occurrence matrix on 2,748 twin studies published between 1958 and 2012.

Each colored cell represents two authors who appeared on the same paper; darker cells indicate authors that co-published more frequently. The filter of at least 25 papers per author was set for readability. The web application MaTCH has an interactive version of this matrix.

Supplementary Figure 2 Funnel plots across all traits for twin correlations and variance components.

Z, Z-converted correlation; MZ, monozygotic twins; DZ, dizygotic twins; DZSS, DZ same-sex twins; MZM, MZ male twins; MZF, MZ female twins; DZM, DZ male twins; DZF, DZ female twins; DOS, DZ opposite-sex twins; h2, heritability; c2, shared environment; h2 same sex; c2 same sex; h2 males; c2 males; h2 female; c2 females.

Supplementary Figure 3 Funnel plots for rMZ across the major trait domains.

The plots denote the relationship between the Z-transformed rMZ and its standard error. SE, standard error.

Supplementary Figure 4 Funnel plots for rDZ across the major trait domains.

The plots denote the relationship between the Z-transformed rDZ and its standard error. SE, standard error.

Supplementary Figure 5 Funnel plots for h2 across the major trait domains.

The plots denote the relationship between the Z-transformed h2 and its standard error. SE, standard error.

Supplementary Figure 6 Funnel plots for c2 across the major trait domains.

The plots denote the relationship between the Z-transformed c2 and its standard error. SE, standard error.

Supplementary Figure 7 Distribution of twin correlations and variance components in full and best models across all traits from 2,748 studies.

rMZ, monozygotic twin correlation; rDZ, dizygotic twin correlation; rDZSS, DZ same-sex twin correlation; rMZM, MZ male twin correlation; rMZF, MZ female twin correlation; rDZM, DZ male twin correlation; rDZF, DZ female twin correlation; rDOS, DZ opposite-sex twin correlation; h2, heritability; c2, shared environment; h2 same sex;c2 same sex; h2 males; c2 males; h2 females; c2 females. “BEST” denotes estimates from the most parsimonious models per study. All other estimates are from “FULL” models.

Supplementary Figure 8 Distribution of differences between MZ and DZ correlations.

rMZ, monozygotic twin correlation; rDZ, dizygotic twin correlation; rDZSS, DZ same-sex twin correlation; rMZM, MZ male twin correlation; rMZF, MZ female twin correlation; rDZM, DZ male twin correlation; rDZF, DZ female twin correlation; rDOS, DZ opposite-sex twin correlation.

Supplementary Figure 9 The correlation between variance component estimates (h2 or c2) from maximum-likelihood (BEST or FULL models) (x axis) compared to the least-squares estimates (y axis).

Supplementary Figure 10 The difference between variance components estimates from maximum-likelihood (BEST model) and least-squares (h2, left panel; c2, right panel) for given sample size.

Supplementary Figure 11 Scatterplots of all MZ versus DZ correlations.

Contour lines indicate the density of the data in that region. The lines are ‘heat’ colored from blue to red, indicating increasing data density.

Supplementary Figure 12 QQ plots of the χ2 test statistics for testing the null hypothesis that 2(rMZrDZ) = 0 and 2rDZrMZ = 0 and relationship with sample size.

(a) The deviation from the null hypotheses is quantified with the inflation λ in the QQ plots. (b) Effects as a function of sample size.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–12, Supplementary Note and Supplementary Tables 1–19, 22–24 and 26–31. (PDF 4786 kb)

Supplementary Tables 20, 21, 25, 32 and 33.

Supplementary Tables 20, 21, 25, 32 and 33. (XLSX 609 kb)

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Polderman, T., Benyamin, B., de Leeuw, C. et al. Meta-analysis of the heritability of human traits based on fifty years of twin studies. Nat Genet 47, 702–709 (2015). https://doi.org/10.1038/ng.3285

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