Home LiteratureArticle Details
PMID: 18454194 Published · epublish English Journal Article Research Support, Non-U.S. Gov't Review

Data and theory point to mainly additive genetic variance for complex traits.

PLoS genetics ·Vol. 4 ·No. 2 ·2008-02-29 ·Pages e1000008

Hill WG, Goddard ME, Visscher PM

Abstract

The relative proportion of additive and non-additive variation for complex traits is important in evolutionary biology, medicine, and agriculture. We address a long-standing controversy and paradox about the contribution of non-additive genetic variation, namely that knowledge about biological pathways and gene networks imply that epistasis is important. Yet empirical data across a range of traits and species imply that most genetic variance is additive. We evaluate the evidence from empirical studies of genetic variance components and find that additive variance typically accounts for over half, and often close to 100%, of the total genetic variance. We present new theoretical results, based upon the distribution of allele frequencies under neutral and other population genetic models, that show why this is the case even if there are non-additive effects at the level of gene action. We conclude that interactions at the level of genes are not likely to generate much interaction at the level of variance.

MeSH Terms
Alleles Animals Animals, Domestic/genetics Animals, Laboratory/genetics Epistasis, Genetic Gene Frequency Genes, Dominant Genetic Variation Genetics, Population Humans Models, Genetic Phenotype Quantitative Trait Loci Twin Studies as Topic
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Hill William G
Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom. w.g.hill@ed.ac.uk
Goddard Michael E
Visscher Peter M
Conflict of Interest

The authors have declared that no competing interests exist.

References (53)
53 references, click to expand
  1. Epistasis and balanced polymorphism influencing complex trait variation.
    Nature. 2005 May 5;435(7038):95-8 PMID: 15875023
  2. Evolution of the environmental component of the phenotypic variance: stabilizing selection in changing environments and the cost of homogeneity.
    Evolution. 2005 Jun;59(6):1237-44 PMID: 16050100
  3. Evolution in Mendelian Populations.
    Genetics. 1931 Mar;16(2):97-159 PMID: 17246615
  4. The effects of population size and selection intensity in selection for a quantitative character in Drosophila. I. Short-term response to selection.
    Genet Res. 1968 Dec;12(3):237-48 PMID: 5729523
  5. Multivariate genetic analysis of sex limitation and G x E interaction.
    Twin Res Hum Genet. 2006 Aug;9(4):481-9 PMID: 16899154
  6. The correlation between relatives in a random mating population.
    Proc R Soc Lond B Biol Sci. 1954 Dec 15;143(910):102-13 PMID: 13224653
  7. Genome-wide strategies for detecting multiple loci that influence complex diseases.
    Nat Genet. 2005 Apr;37(4):413-7 PMID: 15793588
  8. A general method of detecting additive, dominance and epistatic variation for metrical traits.
    Heredity (Edinb). 1968 Aug;23(3):403-9 PMID: 5250122
  9. Twin studies of adult psychiatric and substance dependence disorders: are they biased by differences in the environmental experiences of monozygotic and dizygotic twins in childhood and adolescence?
    Psychol Med. 1998 May;28(3):625-33 PMID: 9626718
  10. The role of epistasis in the manifestation of heterosis: a systems-oriented approach.
    Genetics. 2007 Nov;177(3):1815-25 PMID: 18039883
  11. An integrative genomics approach to infer causal associations between gene expression and disease.
    Nat Genet. 2005 Jul;37(7):710-7 PMID: 15965475
  12. The additive genetic variance after bottlenecks is affected by the number of loci involved in epistatic interactions.
    Evolution. 2003 Apr;57(4):706-16 PMID: 12778542
  13. Genetics of quantitative traits in Arabidopsis thaliana.
    Heredity (Edinb). 2003 Nov;91(5):456-64 PMID: 14576738
  14. Simultaneous mapping of epistatic QTL in DU6i x DBA/2 mice.
    Mamm Genome. 2005 Jul;16(7):481-94 PMID: 16151693
  15. The effects of population size and selection intesnity in selection for a quantitative character in Drosophila. II. Long-term response to selection.
    Genet Res. 1968 Dec;12(3):249-66 PMID: 5713599
  16. Effects of genetic drift on variance components under a general model of epistasis.
    Evolution. 2004 Oct;58(10):2111-32 PMID: 15562679
  17. Comparing evolvability and variability of quantitative traits.
    Genetics. 1992 Jan;130(1):195-204 PMID: 1732160
  18. Parental treatment and the equal environment assumption in twin studies of psychiatric illness.
    Psychol Med. 1994 Aug;24(3):579-90 PMID: 7991740
  19. EPISTASIS AS A SOURCE OF INCREASED ADDITIVE GENETIC VARIANCE AT POPULATION BOTTLENECKS.
    Evolution. 1996 Jun;50(3):1042-1051 PMID: 28565298
  20. Genetic variation for total fitness in Drosophila melanogaster.
    Proc Biol Sci. 1997 Feb 22;264(1379):191-9 PMID: 9061969
  21. Epistasis and its contribution to genetic variance components.
    Genetics. 1995 Mar;139(3):1455-61 PMID: 7768453
  22. A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants.
    Science. 2007 Jun 1;316(5829):1341-5 PMID: 17463248
  23. Two-stage two-locus models in genome-wide association.
    PLoS Genet. 2006 Sep 22;2(9):e157 PMID: 17002500
  24. Quantitative genetics of finger-print patterns.
    Br Med Bull. 1961 Sep;17:247-50 PMID: 13715551
  25. Inbreeding depression: tests of the overdominance and partial dominance hypotheses.
    Evolution. 2002 Apr;56(4):768-75 PMID: 12038534
  26. Dynamic genetic interactions determine odor-guided behavior in Drosophila melanogaster.
    Genetics. 2006 Nov;174(3):1349-63 PMID: 17028343
  27. A common variant of HMGA2 is associated with adult and childhood height in the general population.
    Nat Genet. 2007 Oct;39(10):1245-50 PMID: 17767157
  28. Simultaneous mapping of epistatic QTL in chickens reveals clusters of QTL pairs with similar genetic effects on growth.
    Genet Res. 2004 Jun;83(3):197-209 PMID: 15462413
  29. Theoretical models of selection and mutation on quantitative traits.
    Philos Trans R Soc Lond B Biol Sci. 2005 Jul 29;360(1459):1411-25 PMID: 16048784
  30. An Extension of the Concept of Partitioning Hereditary Variance for Analysis of Covariances among Relatives When Epistasis Is Present.
    Genetics. 1954 Nov;39(6):859-82 PMID: 17247525
  31. Estimating genetic parameters in natural populations using the "animal model".
    Philos Trans R Soc Lond B Biol Sci. 2004 Jun 29;359(1446):873-90 PMID: 15306404
  32. Effects of selection on growth, body composition and food intake in mice. I. Responses in selected traits.
    Genet Res. 1984 Feb;43(1):75-92 PMID: 6724302
  33. Predictions of patterns of response to artificial selection in lines derived from natural populations.
    Genetics. 2005 Jan;169(1):411-25 PMID: 15677752
  34. Epistasis: too often neglected in complex trait studies?
    Nat Rev Genet. 2004 Aug;5(8):618-25 PMID: 15266344
  35. Models of quantitative variation of flux in metabolic pathways.
    Genetics. 1989 Apr;121(4):869-76 PMID: 2721937
  36. The genetic architecture of response to long-term artificial selection for oil concentration in the maize kernel.
    Genetics. 2004 Dec;168(4):2141-55 PMID: 15611182
  37. Natural selection and quantitative genetics of life-history traits in Western women: a twin study.
    Evolution. 2001 Feb;55(2):423-35 PMID: 11308097
  38. Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels.
    Science. 2007 Jun 1;316(5829):1331-6 PMID: 17463246
  39. Heritability of fitness in a wild mammal population.
    Proc Natl Acad Sci U S A. 2000 Jan 18;97(2):698-703 PMID: 10639142
  40. Estimation of genetic parameters for litter size in Canadian Yorkshire and Landrace swine with each parity of farrowing treated as a different trait.
    J Anim Sci. 1995 Oct;73(10):2959-70 PMID: 8617666
  41. Drosophila bristles and the nature of quantitative genetic variation.
    Philos Trans R Soc Lond B Biol Sci. 2005 Jul 29;360(1459):1513-27 PMID: 16108138
  42. Will population bottlenecks and multilocus epistasis increase additive genetic variance?
    Evolution. 2006 Sep;60(9):1763-76 PMID: 17089962
  43. ROLE OF EPISTASIS AND OVERDOMINANCE IN STABILITY OF EQUILIBRIA WITH SELECTION.
    Proc Natl Acad Sci U S A. 1959 Jul;45(7):984-9 PMID: 16590492
  44. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls.
    Nature. 2007 Jun 7;447(7145):661-78 PMID: 17554300
  45. Prediction of effects of genetic drift on variance components under a general model of epistasis.
    Theor Popul Biol. 2006 Aug;70(1):56-62 PMID: 16360188
  46. Natural selection and the heritability of fitness components.
    Heredity (Edinb). 1987 Oct;59 ( Pt 2):181-97 PMID: 3316130
  47. Understanding quantitative genetic variation.
    Nat Rev Genet. 2002 Jan;3(1):11-21 PMID: 11823787
  48. Analysis of response to 20 generations of selection for body composition in mice: fit to infinitesimal model assumptions.
    Genet Sel Evol. 2000 Jan-Feb;32(1):3-21 PMID: 14736404
  49. The genetic architecture of quantitative traits: lessons from Drosophila.
    Curr Opin Genet Dev. 2004 Jun;14(3):253-7 PMID: 15172667
  50. A genome-wide association study identifies novel risk loci for type 2 diabetes.
    Nature. 2007 Feb 22;445(7130):881-5 PMID: 17293876
  51. The Effect of Inbreeding on the Variation Due to Recessive Genes.
    Genetics. 1952 Mar;37(2):189-207 PMID: 17247385
  52. Modeling quantitative trait Loci and interpretation of models.
    Genetics. 2005 Mar;169(3):1711-25 PMID: 15654105
  53. The control of flux.
    Symp Soc Exp Biol. 1973;27:65-104 PMID: 4148886
Article Info
Journal
PLoS genetics
Abbr.
PLoS Genet
ISSN
1553-7404
Published
2008-02-29
Epub
2008-00-29
Pages
e1000008
Language
English
Region
United States
NLM ID
101239074
PMCID
PMC2265475
Subset
IM
Grants
Medical Research Council · United Kingdom
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com