Review Article | Published:

Heritability in the genomics era — concepts and misconceptions

Nature Reviews Genetics volume 9, pages 255266 (2008) | Download Citation

Abstract

Heritability allows a comparison of the relative importance of genes and environment to the variation of traits within and across populations. The concept of heritability and its definition as an estimable, dimensionless population parameter was introduced by Sewall Wright and Ronald Fisher nearly a century ago. Despite continuous misunderstandings and controversies over its use and application, heritability remains key to the response to selection in evolutionary biology and agriculture, and to the prediction of disease risk in medicine. Recent reports of substantial heritability for gene expression and new estimation methods using marker data highlight the relevance of heritability in the genomics era.

Key points

  • Heritability, the proportion of variation in a particular trait that is attributable to genetic factors, is a fundamental parameter in genetics. First introduced by Sewall Wright and Ronald Fisher nearly a century ago, it is key to the response to selection in evolutionary biology and agriculture, and to the prediction of disease risk in medicine.

  • Heritability is not necessarily constant in a population. Changes in the method of measurement, environmental change and the effects of migration, selection and inbreeding all can alter heritability.

  • The use of high-density genetic marker technologies allows novel estimation methods of heritability, for example, estimation in unpedigreed populations and estimation within families — free of assumptions about variation between families.

  • The estimation of heritability for new phenotypes — those that can be measured with recently developed technologies — provides knowledge about the nature of between-individual differences in core biological processes. For example, amounts of gene expression, brain scanning measurements, the length of telomeres and biochemical compounds measured by mass spectrometry show substantial heritability.

  • Heritabilities are often surprisingly large and at present there is no consensus theory to explain why heritabilities have the values they do. Fortunately, the incredible pace of gene–phenotype discoveries in many species will allow new insights to these questions in the near future.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    Coming to terms with heritability. Genetica 99, 89–96 (1997).

  2. 2.

    & Genetics and analysis of quantitative traits (Sinauer Associates, Sunderland, Massachusetts, 1998).

  3. 3.

    & Introduction to Quantitative Genetics (Longman, Harlow, 1996). References 2 and 3 are introductory and advanced books, respectively, on the theory and application of quantitative genetics across species: they are superb scholarly works and are much more than text books.

  4. 4.

    , , , Analyses of published genetic parameter estimates for beef production traits. 1. Heritability. Animal Breeding Abstracts 62, 309–338. (1994).

  5. 5.

    Heritability: one word, three concepts. Biometrics 39, 465–477 (1983).

  6. 6.

    & Mixed model methodology for farm and ranch beef cattle testing programs. Journal of Anim. Sci. 51, 1277–1287 (1980).

  7. 7.

    Estimating genetic parameters in natural populations using the 'animal model'. Philos. Trans. R. Soc. Lond., B, Biol. Sci. 359, 873–890 (2004).

  8. 8.

    & Multipoint quantitative-trait linkage analysis in general pedigrees. Am. J. Hum. Genet. 62, 1198–1211 (1998).

  9. 9.

    & Recovery of interblock information when block sizes are unqual. Biometrika 58, 545–555 (1971).

  10. 10.

    & Models to estimate maternal effects for juvenile body weight in broiler chickens. Genet. Sel. Evol. 29, 225–249 (1997).

  11. 11.

    et al. Heritability of fitness in a wild mammal population. Proc. Natl Acad. Sci. USA 97, 698–703 (2000).

  12. 12.

    , , & Bias, precision and heritability of self-reported and clinically measured height in Australian twins. Hum. Genet. 120, 571–580 (2006).

  13. 13.

    et al. Replicated effects of sex and genotype on gene expression in human lymphoblastoid cell lines. Hum. Mol. Genet. 16, 364–373 (2007).

  14. 14.

    Maximum likelihood estimation of variance components for a multivariate mixed model with equal design matrices. Biometrics 41, 153–165 (1985).

  15. 15.

    & Likelihood, Bayesian, and MCMC Methods in Quantitative Genetics (Springer, New York, 2002).

  16. 16.

    Inheritance of liability to certain diseases estimated from incidence among relatives. Ann. Hum. Genet. 29, 51–76 (1965).

  17. 17.

    The genetics of schizophrenia. PLoS Med. 2, e212 (2005).

  18. 18.

    , & Genetic epidemiology of major depression: review and meta-analysis. Am. J. Psychiatry 157, 1552–1562 (2000).

  19. 19.

    & Heritability of threshold characters. Genetics 35, 212–236 (1950). A paper that is perhaps most famous for its appendix, written by Alan Robertson, that showed the approximate relationship between heritability on the observed and underlying scale for dichotomous traits.

  20. 20.

    , & Prediction of individual genetic risk to disease from genome-wide association studies. Genome Res. 17, 1520–1528 (2007).

  21. 21.

    The Genetical Theory of Natural Selection (Clarendon, Oxford, 1930).

  22. 22.

    Quantitative genetic analysis of multivariate evolution, applied to brain:body size allometry. Evolution 33, 402–416 (1979).

  23. 23.

    & The measurement of selection on correlated characters. Evolution 37, 1210–1226 (1983).

  24. 24.

    A mathematical model of culling process in dairy cattle. Anim. Prod. 8, 95–108 (1966).

  25. 25.

    et al. Antler size in red deer: heritability and selection but no evolution. Evolution 56, 1683–1695 (2002).

  26. 26.

    A tale of two matrices: multivariate approaches in evolutionary biology. J. Evol. Biol. 20, 1–8 (2007).

  27. 27.

    & Power and potential bias in field studies of natural selection. Evolution 58, 479–485 (2004).

  28. 28.

    , & Heritabilities and genetic correlations for the 1st 3 lactations from records subject to culling. J. Dairy Sci. 62, 1784–1790 (1979).

  29. 29.

    et al. Genetic parameters for body condition score, body weight, milk yield, and fertility estimated using random regression models. J. Dairy Sci. 86, 3704–3717 (2003).

  30. 30.

    & Heritable variation and evolution under favourable and unfavourable conditions. Trends Ecol. Evol. 14, 96–101 (1999).

  31. 31.

    & Environmental quality and evolutionary potential: lessons from wild populations. Proc. R. Soc. Lond., B, Biol. Sci. 272, 1415–1425 (2005).

  32. 32.

    & The quantitative genetics of wing dimorphism under laboratory and 'field' conditions in the cricket Gryllus pennsylvanicus. Heredity 78, 235–240 (1997).

  33. 33.

    , , & Heritability of milk yield and composition at different levels and variability of production. Anim. Prod. 36, 59–68 (1983).

  34. 34.

    , & Estimation of genetic and environmental variances for fat yield in individual herds and an investigation into heterogeneity of variance between herds. Livest. Prod. Sci. 28, 273–290 (1991).

  35. 35.

    Wilson, A. J. et al. Environmental coupling of selection and heritability limits evolution. PLoS Biol. 4, e216 (2006).

  36. 36.

    , , , & Socioeconomic status modifies heritability of IQ in young children. Psychol. Sci. 14, 623–628 (2003).

  37. 37.

    Effect of selection on genetic variability. Am. Nat. 105, 201–211 (1971).

  38. 38.

    & Prediction of rates of inbreeding in selected populations. Genet. Res. 55, 41–54 (1990).

  39. 39.

    , , & Estimation of changes in genetic parameters in selected lines of mice using REML with an animal model.1. Lean mass. Heredity 69, 352–360 (1992).

  40. 40.

    & The changes in genetic and environmental variance with inbreeding in Drosophila melanogaster. Genetics 152, 345–353 (1999).

  41. 41.

    , & Inbreeding: its effect on response to selection for pupal weight and the heritable variance in fitness in the flour beetle, Tribolium castaneum. Evolution 50, 723–733 (1996).

  42. 42.

    , & Genetic components of variation in Nemophila menziesii undergoing inbreeding: morphology and flowering time. Genetics 150, 1649–1661 (1998).

  43. 43.

    & Effects of genetic drift on variance components under a general model of epistasis. Evolution Int. J. Org. Evolution 58, 2111–2132 (2004).

  44. 44.

    The effect of inbreeding on the variation due to recessive genes. Genetics 37, 189–207 (1952).

  45. 45.

    & The distribution of phenotypic variance with inbreeding. Evolution 53, 1143–1156 (1999).

  46. 46.

    Predictions of response to artificial selection from new mutations. Genet. Res. 40, 255–278 (1982).

  47. 47.

    , & Maize selection passes the century mark: a unique resource for 21st century genomics. Trends Plant Sci. 9, 358–364 (2004). This paper is one of the few examples in which heritability, in this case of maize protein and oil percentage in corn, has been estimated over many generations of selection in a long-term selection experiments. Genetic variance has been maintained despite an effective population size of 96 at most.

  48. 48.

    & Understanding quantitative genetic variation. Nature Rev. Genet. 3, 11–21 (2002).

  49. 49.

    Marker-based method for inferences about quantitative inheritance in natural populations. Evolution 50, 1062–1073 (1996). In this paper, Ritland proposed how the estimation of relatedness from molecular markers can be combined with phenotypic resemblance to estimate heritability in natural populations when pedigree information is not available.

  50. 50.

    The estimation of genetic relationships using molecular markers and their efficiency in estimating heritability in natural populations. Philos. Trans. R. Soc. Lond., B, Biol. Sci. 360, 1457–1467 (2005).

  51. 51.

    , & Estimating variance components in natural populations using inferred relationships. Heredity 84, 427–436 (2000).

  52. 52.

    Marker-inferred relatedness as a tool for detecting heritability in nature. Mol. Ecol. 9, 1195–1204 (2000).

  53. 53.

    , & A novel method for estimating heritability using molecular markers. Heredity 80, 218–224 (1998).

  54. 54.

    & Inferences about quantitative inheritance based on natural population structure in the yellow monkeyflower, Mimulus guttatus. Evolution 50, 1074–1082 (1996).

  55. 55.

    , & The use of marker-based relationship information to estimate the heritability of body weight in a natural population: a cautionary tale. J. Evol. Biol. 15, 92–99 (2002).

  56. 56.

    et al. Assumption-free estimation of heritability from genome-wide identity by descent sharing between full siblings. PLoS Genet. 2, e41 (2006). This paper demonstrated by theory and application that, when using genetic markers, heritability can be estimated from within-family information only, free of assumptions and the potential bias of between-family effects.

  57. 57.

    , , & Merlin — rapid analysis of dense genetic maps using sparse gene flow trees. Nature Genet. 30, 97–101 (2002).

  58. 58.

    Variation in genetic identity among relatives. Hum. Hered. 46, 61–70 (1996).

  59. 59.

    Variation in genetic identity within kinships. Heredity 71, 652–653 (1993).

  60. 60.

    & Application of a recombination model in calculating the variance of sib pair genetic identity. Ann. Hum. Genet. 43, 177–186 (1979).

  61. 61.

    Population genetics: separating nurture from nature in estimating heritability. Heredity 97, 256–257 (2006).

  62. 62.

    et al. Genome partitioning of genetic variation for height from 11,214 sibling pairs. Am. J. Hum. Genet. 81, 1104–1110 (2007).

  63. 63.

    , , & Genetic dissection of transcriptional regulation in budding yeast. Science 296, 752–5 (2002).

  64. 64.

    et al. Genetics of gene expression surveyed in maize, mouse and man. Nature 422, 297–302 (2003).

  65. 65.

    et al. Natural variation in human gene expression assessed in lymphoblastoid cells. Nature Genet. 33, 422–425 (2003). References 64 and 65 are two landmark papers that show that heritability for gene expression is widespread, across multiple species.

  66. 66.

    & Genetical genomics: the added value from segregation. Trends Genet. 17, 388–391 (2001).

  67. 67.

    & Genetics of global gene expression. Nature Rev. Genet. 7, 862–872 (2006).

  68. 68.

    et al. Global eQTL mapping reveals the complex genetic architecture of transcript-level variation in Arabidopsis. Genetics 175, 1441–50 (2007).

  69. 69.

    et al. Global eQTL mapping reveals the complex genetic architecture of transcript-level variation in Arabidopsis and modulates expression of PTGER4. PLoS Genet. 3, e58 (2007).

  70. 70.

    et al. Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma. Nature 448, 470–473 (2007).

  71. 71.

    , & Data and theory point to mainly additive genetic variance for complex traits PLoS Genet. (in the press).

  72. 72.

    & Evolution of the environmental component of the phenotypic variance: stabilizing selection in changing environments and the cost of homogeneity. Evolution Int. J. Org. Evolution 59, 1237–1244 (2005).

  73. 73.

    & Mutation selection balance for environmental variance. Am. Nat. (in the press).

  74. 74.

    & Long-term selection for 8-week body-weight in chickens — direct and correlated responses. Theor. App. Genet. 71, 305–313 (1985).

  75. 75.

    Covariance between relatives for characters composed of components contributed by related individuals. Biometrics 19, 18–27 (1963).

  76. 76.

    et al. Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 301, 386–389 (2003).

  77. 77.

    Secular trends in growth. Proc. Nutr. Soc. 59, 317–324 (2000).

  78. 78.

    & The mysterious trend in American heights in the 20th century. Ann. Hum. Biol. 34, 206–215 (2007).

  79. 79.

    Comparing evolvability and variability of quantitative traits. Genetics 130, 195–204 (1992). This paper proposes that the potential to respond to natural or artificial selection, termed evolvability, can be expressed as an additive genetic coefficient of variation, with empirical data to show that fitness-related traits display surprisingly high coefficients.

  80. 80.

    , , & Genetic variation for total fitness in Drosophila melanogaster. Proc. R. Soc. Lond., B, Biol. Sci. 264, 191–199 (1997).

  81. 81.

    et al. Natural selection and quantitative genetics of life-history traits in Western women: a twin study. Evolution Int. J. Org. Evolution 55, 423–435 (2001).

  82. 82.

    & in The Challenge of Genetic Change in Animal Production (eds Hill, W. G. et al.) (British Society of Animal Science, Edinburgh, 2000).

  83. 83.

    Massive IQ gains in 14 nations — what IQ tests really measure. Psychol. Bull. 101, 171–191 (1987).

  84. 84.

    & Evidence for a major gene for rapid postweaning growth in mice. Genet. Res. 44, 293–308 (1984).

  85. 85.

    et al. Regulatory variation at glypican 3 underlies a major growth QTL in mice. PLoS Biol. 3, e135 (2005).

  86. 86.

    et al. A common variant of HMGA2 is associated with adult and childhood height in the general population. Nature Genet. 39, 1245–1250 (2007).

  87. 87.

    The relative importance of heredity and environment in determining the piebald pattern of guinea-pigs. Proc. Natl Acad. Sci. USA 6, 320–332 (1920). This paper is one of the earliest applications of Wright's method of path analysis and the first time the term h2 is used and defined as the 'degree of determination by heredity'.

  88. 88.

    The correlation between relatives on the supposition of Mendelian inheritance. Trans. Roy. Soc. Edin. 52, 399–433 (1918). This is a classic and landmark paper that reconciled Mendelian and biometrical genetics and founded quantitative genetics theory.

  89. 89.

    Intra-sire correlations or regressions of offspring on dam as a method of estimating heritability of characteristics. Proc. Am. Soc. Anim. Prod. 33, 293–301 (1940).

  90. 90.

    Logical, epistemological and statistical aspects of nature–nurture data interpretation. Biometrics 34, 1–23 (1978).

  91. 91.

    Annotation: the analysis of variance and the analysis of causes. Am. J. Hum. Genet. 26, 400–411 (1974).

  92. 92.

    Lessons from The Bell Curve. J. Polit. Econ. 103, 1091–1120 (1995).

  93. 93.

    & The Bell Curve: Intelligence and Class Structure in American Life (The Free Press, New York, 1994).

  94. 94.

    , & Genetics of intelligence. Eur. J. Hum. Genet. 14, 690–700 (2006).

  95. 95.

    , , & Genetic and environmental influences on the development of intelligence. Behav. Genet. 32, 237–249 (2002).

  96. 96.

    et al. Substantial genetic influence on cognitive abilities in twins 80 or more years old. Science 276, 1560–1563 (1997).

  97. 97.

    & Twin studies, heritability, and intelligence. Science 278, 1383–1384 (1997).

  98. 98.

    , & The heritability of IQ. Nature 388, 468–471 (1997).

  99. 99.

    & Heritability of threshold characters. Genetics 35, 212–236 (1950).

  100. 100.

    et al. The association between brain volume and intelligence is of genetic origin. Nature Neurosci. 5, 83–84 (2002).

  101. 101.

    et al. Telomere length as an indicator of biological aging — the gender effect and relation with pulse pressure and pulse wave velocity. Hypertension 37, 381–385 (2001).

  102. 102.

    & Telomere maintenance and disease. Lancet 362, 983–988 (2003).

  103. 103.

    et al. Mapping genetic loci that determine leukocyte telomere length in a large sample of unselected female sibling pairs. Am. J. Hum. Genet. 78, 480–486 (2006).

  104. 104.

    et al. Telomere length inversely correlates with pulse pressure and is highly familial. Hypertension 36, 195–200 (2000).

  105. 105.

    , & Genetic determination of telomere size in humans: a twin study of three age groups. Am. J. Hum. Genet. 55, 876–882 (1994).

  106. 106.

    et al. The genetics of plant metabolism. Nature Genet. 38, 842–849 (2006).

  107. 107.

    & Quantitative genetics and fitness: lessons from Drosophila. Heredity 58, 103–118 (1987).

  108. 108.

    Quantitative genetics of zooplankton life histories. Experientia 51, 454–464 (1995).

  109. 109.

    & Phenotypic variation and population structuring in Atlantic salmon in fluctuating environments. J. Fish Biol. 69, 232–232 (2006).

  110. 110.

    Expression of genetic variation in body size of the collared flycatcher under different environmental conditions. Evolution 51, 526–536 (1997).

  111. 111.

    & Natural selection and the heritability of fitness components. Heredity 59, 181–197 (1987).

  112. 112.

    Genetic parameters for tropical beef-cattle in northern Australia — a Review. Aust. J. Agric. Res. 44, 179–198 (1993).

  113. 113.

    Determinants of variation in adult body height. J. Biosoc. Sci. 35, 263–285 (2003).

  114. 114.

    Breeding plans for rainbow trout. Aquaculture 100, 73–83 (1992).

  115. 115.

    Genetics of sow reproduction, including puberty, oestrus, pregnancy, farrowing and lactation. Livest. Prod. Sci. 66, 1–12 (2000).

Download references

Acknowledgements

The authors are supported by the Australian National Health and Medical Research Council (grants 389892, 442915 and 443011) and the Australian Research Council (grant DP0770096). We thank I. Deary and the referees for their many comments on earlier versions of the manuscript.

Author information

Affiliations

  1. Queensland Institute of Medical Research, Royal Brisbane Hospital Post Office, Brisbane 4029, Queensland, Australia.

    • Peter M. Visscher
    •  & Naomi R. Wray
  2. Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, West Mains Road, Edinburgh, EH9 3JT, UK.

    • William G. Hill

Authors

  1. Search for Peter M. Visscher in:

  2. Search for William G. Hill in:

  3. Search for Naomi R. Wray in:

Corresponding author

Correspondence to Peter M. Visscher.

Glossary

Linear mixed model

A statistical model in which the dependent variable is a linear function of both fixed and random independent variables. Fixed effects are constant following the taking of repeated samples, whereas random effects are a sample from a distribution of effects.

Sampling variance

The variation of a parameter estimate across repeated samples due to finite sample size.

Bayesian estimation

An estimation method that combines prior information and observed data to draw statistical inference.

Confounding

The impossibility of separating the effect of two or more causal factors on an observed variable.

Assortative mating

The tendency of mates to resemble each other in phenotype.

Truncation selection

Selection of individuals with trait values equal to or greater than some threshold as parents of the next generation.

Stabilizing selection

Selection, either natural or artificial, of individuals with trait values in the middle of the distribution as parents of the next generation.

Gametic disequilibrium

The non-random association of alleles at different loci (also termed linkage disequilibrium).

About this article

Publication history

Published

DOI

https://doi.org/10.1038/nrg2322

Further reading