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  • Perspective
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Concepts, estimation and interpretation of SNP-based heritability

Nature Genetics volume 49, pages 1304–1310 (2017)Cite this article

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Abstract

Narrow-sense heritability (h2) is an important genetic parameter that quantifies the proportion of phenotypic variance in a trait attributable to the additive genetic variation generated by all causal variants. Estimation of h2 previously relied on closely related individuals, but recent developments allow estimation of the variance explained by all SNPs used in a genome-wide association study (GWAS) in conventionally unrelated individuals, that is, the SNP-based heritability (). In this Perspective, we discuss recently developed methods to estimate for a complex trait (and genetic correlation between traits) using individual-level or summary GWAS data. We discuss issues that could influence the accuracy of , definitions, assumptions and interpretations of the models, and pitfalls of misusing the methods and misinterpreting the models and results.

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Figure 1: Interpretation of estimated genetic variance depends on ascertainment of the sample.
Figure 2: Relationship between SNP-based heritability on the liability scale (h2SNP(l)) and SNP-based heritability estimated from case–control samples.
Figure 3: Estimation of genetic variance depends on ascertainment of SNPs and genetic architecture.
Figure 4: Multiple-component GREML or HE regression for sets of SNPs stratified by MAF.

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Acknowledgements

We thank A. Price for his constructive and helpful comments on an earlier version of the manuscript. This research was supported by the Australian National Health and Medical Research Council (1078901, 1078037 and 1113400), the Australian Research Council (DP160101343), the US National Institutes of Health (GM099568 and MH100141-01), and the Sylvia & Charles Viertel Charitable Foundation (Senior Medical Research Fellowship). This research has been conducted using data from dbGaP (accessions phs000090.v3.p1 and phs000091.v2.p1), the UK10K Project and the UK Biobank Resource (application number 12514). A full list of acknowledgments to these data sets can be found in the Supplementary Note.

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Authors and Affiliations

  1. Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia

    Jian Yang, Jian Zeng, Naomi R Wray & Peter M Visscher

  2. Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia

    Jian Yang, Naomi R Wray & Peter M Visscher

  3. Faculty of Veterinary and Agricultural Science, University of Melbourne, Parkville, Victoria, Australia

    Michael E Goddard

  4. Biosciences Research Division, Department of Economic Development, Jobs, Transport and Resources, Bundoora, Victoria, Australia

    Michael E Goddard

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Correspondence to Jian Yang or Peter M Visscher.

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Yang, J., Zeng, J., Goddard, M. et al. Concepts, estimation and interpretation of SNP-based heritability. Nat Genet 49, 1304–1310 (2017). https://doi.org/10.1038/ng.3941

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