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A twin-pronged attack on complex traits

Nature Geneticsvolume 17pages387392 (1997) | Download Citation

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Abstract

Before one starts the hunt for quantitative trait loci (QTLs) for a complex trait it is necessary to show that the trait is genetically influenced. This evidence is most likely to come from the classical twin study—the demonstration that monozygotic twins are more similar for the trait than dizygotic twins. The strengths and weaknesses of twin studies are discussed, and it is suggested that, far from becoming irrelevant with advances in molecular biology, they can improve the efficiency of QTL detection and play an important role in unravelling developmental genetic mechanisms

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References

  1. 1

    Heston, L.L. Psychiatric disorders in foster-home reared children of schizophrenic mothers, fir. J. Psychiatry 112, 819–825 (1966).

  2. 2

    Goodwin, D.W. et al. Drinking problems in adopted and nonadopted sons of alcoholic. Arch. Gen. Psychiatry 31, 164–169 (1974).

  3. 3

    Bulmer, M.G., Biology of Twinning in Man (Oxford University Press, Oxford, UK, 1970).

  4. 4

    Kendler, K.S. et al. A test of the equal-environment assumption in twin studies of psychiatric illness. Behav. Genet. 23, 21–27 (1993).

  5. 5

    Hopper, J.L. Genes for osteoarthritis: interpreting twin data. BMJ 312, 943–944 (1996).

  6. 6

    Folstein, S. & Rutter, M. Genetic influences and infantile autism. Nature 265, 726–728 (1977).

  7. 7

    Stevenson, J. Evidence for a genetic etiology in hyperactivity in children. Behav. Genet 22, 337–344 (1992).

  8. 8

    Ebers, G.C. et al. A population-based study of multiple sclerosis in twins. N. Engl. J. Med. 315, 1638–1642 (1986).

  9. 9

    Ebers, G.C. et al. A full genome search in multiple sclerosis. Nature Genet. 13, 472–476 (1996).

  10. 10

    Bailey, J.M. & Pillard, R.C. A genetic study of male sexual orientation. Arch. Gen. Psychiatry 48, 1089–1096 (1991).

  11. 11

    Bailey, J.M., Pillard, R.C., Neale, M.C. & Agyei, Y. Heritable factors influence sexual orientation in women. Arch. Gen. Psychiatry 5O, 217–223 (1993).

  12. 12

    Bailey, J.M., Dunne, M.P. & Martin, N.G. Sex differencesJn the distribution and determinants of sexual orientation in a national twin sample (submitted).

  13. 13

    Plomin, R., Corley, R., DeFries, J.C. & Fulker, D.W. Individual differences in television viewing in early childhood: nature as well as nurture. Psychol. Sci. 6, 371–377 (1990).

  14. 14

    Martin, N.G. et al. Transmission of social attitudes. Proc. Natl. Acad. Sci. USA. 83, 4364–4368 (1986).

  15. 15

    McGue, M. & Lykken, D.T. Genetic influence on risk of divorce. Psychol. Sci. 3, 368–373 (1991).

  16. 16

    Lykken, D.T. & Tellegen, A. Happiness is a stochastic phenomenon. Psychol. Sci. 7, 186–189 (1996).

  17. 17

    Rende, R.D., Plomin, R. & Vandenberg, S.G. Who discovered the twin method? Behav. Genet. 20, 277–285 (1990).

  18. 18

    Cardon, L.R. et al. Quantitative trait locus for reading disability: correction. Science. 268, 1553 (1995).

  19. 19

    Jinks, J.L. & Fulker, D.W. Comparison of the biometrical genetical, MAVA and classicalal approaches to the analysis of human behavior. Psychol. Bull. 73, 311–349 (1970).

  20. 20

    Eaves, L.J., Last, K., Martin, N.G. & Jinks, J.L. A progressive approach to non-additivity and genotype-environmental covariance in the analysis of human differences, fir. J. Math. Statist. Psychol. 30, 1–42 (1977).

  21. 21

    Eaves, L.J., Last, K., Young, P.A. & Martin, N.G. Model-fitting approaches to the analysis of human behaviour. Heredity. 41, 249–320 (1978).

  22. 22

    Martin, N.G., Eaves, L.J., Kearsey, M.J. & Davies, P. The power of the classical twin study. Heredity. 40, 97–116 (1978).

  23. 23

    Neale, M.C., LJ.& Kendler, K.S. The power of the classical twin study to resolve variation in threshold traits. Behav. Genet. 24, 239–258 (1994).

  24. 24

    Heath, A.C. et al. Genetic and environmental contributions to DSM-IIIR alcohol dependence risk in a national twin sample: no gender differences. Psychol. Med. (in the press).

  25. 25

    Holm, N.V., Hauge, M. & Harvald, B. Etiologic factors of breast cancer elucidated by a study of unselected twins. J. Natl. Cancer Inst. 65, 285–298 (1980).

  26. 26

    Kaprio, J. Lessons from twin studies in Finland. Ann. Med. 26, 135–139 (1994).

  27. 27

    Eaves, L.J. & Meyer, J.M. Locating human quantitative trait loci: guidelines for the selection of sibling pairs for genotyping. behav. Genet. 24, 443–455 (1994).

  28. 28

    Risch, N. & Zhang, H. Extreme discordant sib pairs for mapping quantitative trait loci in humans. Science. 268, 1584–1589 (1995).

  29. 29

    Eaves, L.J., Eysenck, H.J. & Martin, N.G. Genes, Culture and Personality: An Empirical Approach (Academic Press, London, 1989).

  30. 30

    Neale, M.C. & Cardon, L.R. Methodology for Genetic Studies of Twins and Families (Kluwer Academic Publishers, Dordrecht, The Netherlands, 1992).

  31. 31

    Kendler, K.S. & Eaves, L.J. Models for the joint effect of genotype and environment on liability to psychiatric illness. Am. J. Psychiatry. 143, 279–289 (1986).

  32. 32

    Carey, G. Sibling imitation and contrast effects, fiehav. Genet. 16, 319–342 (1986).

  33. 33

    Martin, N.G. & Eaves, L.J. The genetical analysis of covariance structure. Heredity. 38, 79–95 (1977).

  34. 34

    Boomsma, D.I., Martin, N.G., Neale, M.C., eds. Genetic analysis of twin and family data: structural modeling using LISREL. fiehav. Genet. 19, 3–161 (1989).

  35. 35

    Neale, M.C. Mx: Statistical Modeling, 3rd ed. (Box 980126 MCV, Richmond VA 23298, 1997).

  36. 36

    Risch, N. Linkage strategies for genetically complex traits: II. The power of affected relative pairs. Am. J. Hum. Genet. 46, 229–241 (1990).

  37. 37

    Hudziak, J.J. Identifying phenotypes for molecular genetic studies of childhood psychopathology. in The Handbook of Psychiatric Genetics (eds Blum, K. & Noble, E.) 201–218 (CRC Press, Boca Raton, Florida, 1997).

  38. 38

    Boomsma, D.I. Using multivariate genetic modeling to detect pleiotropic quantitative trait loci, fiehav. Genet. 26, 161–166 (1996).

  39. 39

    Kendler, K.S. Major depression and generalized anxiety disorder: same genes (partly) different environments-revisited. Br. J. Psychiatry 168 (Suppl. 30), 68–75 (1996).

  40. 40

    Eaves, L.J., Neale, M.C. & Macs, H. Multivariate multipoint linkage analysis of quantitative trait loci. Behav. Genet. 26, 519–525 (1996).

  41. 41

    Paterson, A.H. et al. Resolution of quantitative traits into Mendelian factors by using a complete linkage map of restriction fragment length polymorphisms. Nature. 335, 721–726 (1988).

  42. 42

    Flint, J. et al. A simple genetic basis for a complex psychological trait in laboratory mice. Science. 269, 1432–1435 (1995).

  43. 43

    Fulker, D.W. & Cherny, S.S. An improved multipoint sib-pair analysis of quantitative traits, flehav. Genet. 26, 527–532 (1996).

  44. 44

    Kruglyak, L. & Lander, E.S. High-resolution genetic mapping of complex traits. Am. J. Hum. Genet. 56, 1212–1223 (1995).

  45. 45

    Collins, F.S. Positional cloning moves from perditional to traditional. Nature Genet. 9, 347–350 (1995).

  46. 46

    Risch, N. & Merikangas, K. The future of genetic studies of complex human diseases. Science. 273, 1516–1517 (1996).

  47. 47

    Bouchard, T.J. et al. Sources of human psychological differences: the Minnesota study of twins reared apart. Science. 268, 223–228 (1990).

  48. 48

    Truett, K.R. et al. A model system for analysis of family resemblance in extended kinships of twins. Behav. Genet. 24, 35–49 (1994).

  49. 49

    Maes, H.H.M., Neale, M.C. & Eaves, L.J. (1997). Genetic and environmental factors in relative body weight and human adiposity. Behav. Genet., (in the press).

  50. 50

    Hennis, B.C. et al. An amino acid polymorphism in histidine-rich glycoprotein (HRG) explains 59% of the variance in plasma HRG levels. Thromb. Haemostasis. 74, 1497–1500 (1995).

  51. 51

    Martin, N.G. et al. Does the PI polymorphism alone control alpha-1-antitrypsin expression. Am. J. Hum Genet. 40, 267–277 (1987).

  52. 52

    Phillips, D.I.W. Twin studies in medical research: can they tell us whether diseases are genetically determined?. Lancet. 341, 1008–1009 (1993).

  53. 53

    Christensen, K., Vaupel, J.W., Holm, N.V. & Yashin, A.I. Mortality among twins after age 6: fetal origins hypothesis versus twin method. BMJ. 310, 432–436 (1995).

  54. 54

    van den Oord, E.J. et al. A twin-singleton comparison of problem behavior in 2–3 year olds. J. Child Psychol. Psychiatry. 36, 449–458 (1995).

  55. 55

    Darlington, C.D. Twin biology. Heredity. 25, 655–657 (1970).

  56. 56

    Loehlin, J.C. & Nichols, R.C., Personality: A Study of 850 Sets of Twins (University of Texas Press, Austin, Texas, 1976).

  57. 57

    Plomin, R. & Daniels, D. Why are children in the same family so different from one another?. Behav. Brain Sci. 10, 1–60 (1987).

  58. 58

    Rowe, D.C., Limits of Family Influence: Genes, Experience, and Behavior (Guilford Press, New York, 1994).

  59. 59

    Torrey, E.F. et al. Prenatal origin of schizophrenia in a subgroup of discordant monozygotic twins. Schizophr. Bull. 20, 425–432 (1994).

  60. 60

    Hopper, J.L. & Seeman, E. The bone density of female twins discordant for tobacco use. N. Engl. J. Med. 330, 387–392 (1994).

  61. 61

    Vernon, P.A., Jang, K.L., Harris, J.A. & McCarthy, J.M. Environmental predictors of personality differences: a twin and sibling study. J. Person. Soc. Psychol. 72, 177–183 (1997).

  62. 62

    Côté, G.B. & Gyftidimou, J. Twinning and mitotic crossing-over: some possibilities and their implications. Am. J. Hum. Genet. 49, 120–130 (1991).

  63. 63

    Machin, G.A. Some causes of genotypic and phenotypic discordance in monozygotic twin pairs. Am. J. Med, Genet. 61, 216–228 (1996).

  64. 64

    Molenaar, P.C.M., Boomsma, D.I. & Dolan, C.V. A third source of developmental differences, fiehav. Genet. 23, 519–524 (1993).

  65. 65

    Richards, C.S. et al. Skewed X inactivation in a female MZ twin results in Duchenne muscular dystrophy. Am. J. Hum. Genet. 46, 672–681 (1990).

  66. 66

    Trejo, V. et al. X chromosome inactivation patterns correlate with fetal-placental anatomy in monozygotic twin pairs: implications for immune relatedness and concordance for autoimmunity. Mol. Med. 1, 62–70 (1994).

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Affiliations

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

    • Nicholas Martin
  2. Psychology Department, Free University, Amsterdam, The Netherlands

    • Dorret Boomsma
  3. Fetal/Genetic Pathologist, The Permanente Medical Group, Northern California Region, Oakland, California, USA

    • Geoffrey Machin

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Correspondence to Nicholas Martin.

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https://doi.org/10.1038/ng1297-387

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