Twin studies and the heritability of MS: a conclusion

Objective The classical twin study has the potential to evaluate the relative contribution of genes and environment and guide further research strategies, provided the sampling and methods of analysis are correct. We wish to review all the more informative twin studies on multiple sclerosis (MS). Methods We examined six large population-based twin studies in MS and calculated indices of heritability (h2), which is the traditional method of assessing genetic contribution to disease and to allow comparison between studies. Results This index was found to vary widely from 0.25 to 0.76 with large confidence intervals that reflect small sample size and prevent robust interpretation. Conclusion Overall the studies support a genetic contribution to disease; however, the imprecision of the heritability estimates and potential biases that they contain mean that very little inference can be drawn its exact size. Given that the magnitude of genetic effect cannot be measured because of the relative infrequency of MS; the consequent difficulty in collecting an informative sample; and in many countries, the lack of a comprehensive twin register, we suggest that further twin prevalence surveys should not be undertaken. Twin studies could be used more effectively in other ways, such as the co-twin case–control approach.

[1]  W. James Gauderman,et al.  Childhood sun exposure influences risk of multiple sclerosis in monozygotic twins , 2007, Neurology.

[2]  D. Paty,et al.  A population-based study of multiple sclerosis in twins. , 1986, The New England journal of medicine.

[3]  B. Weinshenker,et al.  Multiple sclerosis. , 2000, The New England journal of medicine.

[4]  A. Morris,et al.  Evidence for genetic regulation of vitamin D status in twins with multiple sclerosis , 2008, The American journal of clinical nutrition.

[5]  D. McFarlin,et al.  Multiple sclerosis in twins , 1980, Neurology.

[6]  A. Verma,et al.  Risk Alleles for Multiple Sclerosis Identified by a Genomewide Study , 2008 .

[7]  T. Lehtimäki,et al.  Gene expression profiles in Finnish twins with multiple sclerosis , 2006, BMC Medical Genetics.

[8]  N. Martin,et al.  The power of the classical twin study , 1978, Heredity.

[9]  C. Hawkes Twin studies in medicine--what do they tell us? , 1997, QJM : monthly journal of the Association of Physicians.

[10]  A. Tellegen,et al.  Recruitment bias in twin research: The rule of two-thirds reconsidered , 1987, Behavior genetics.

[11]  W. Cendrowski Multiple sclerosis: discordance in three pairs of dizygotic twins. , 1968, Journal of medical genetics.

[12]  M. Devoto,et al.  Variants of ST8SIA1 Are Associated with Risk of Developing Multiple Sclerosis , 2008, PloS one.

[13]  C. Duijn,et al.  EVI5 is a risk gene for multiple sclerosis , 2008, Genes and Immunity.

[14]  T. Spector,et al.  Genetic influences on osteoarthritis in women: a twin study , 1996, BMJ.

[15]  J. Brody,et al.  Twin study of multiple sclerosis , 1978, Neurology.

[16]  A. Ascherio Epstein–Barr virus in the development of multiple sclerosis , 2008, Expert review of neurotherapeutics.

[17]  C. Smith,et al.  Concordance in twins: methods and interpretation. , 1974, American journal of human genetics.

[18]  K. Kyvik,et al.  Concordance for multiple sclerosis in Danish twins: an update of a nationwide study , 2005, Multiple sclerosis.

[19]  A. Sadovnick,et al.  CONCORDANCE IN TWINS AND RECURRENCE IN SIBSHIPS IN MULTIPLE SCLEROSIS , 1982, The Lancet.

[20]  S. Faraone,et al.  Genes, environment and schizophrenia. , 2001, The British journal of psychiatry. Supplement.

[21]  K. Kyvik,et al.  Risk for multiple sclerosis in dizygotic and monozygotic twins , 2005, Multiple sclerosis.

[22]  K. Kendler,et al.  Multivariate genetic analysis of twin-family data on fears: Mx models , 1994, Behavior genetics.

[23]  D. Miller,et al.  The British Isles survey of multiple sclerosis in twins , 1994, Neurology.

[24]  T. Mack,et al.  Differential twin concordance for multiple sclerosis by latitude of birthplace , 2006, Annals of neurology.

[25]  R. Currier,et al.  Possible risk factors in multiple sclerosis as found in a national twin study. , 1982, Archives of neurology.

[26]  I. Elovaara,et al.  Human herpes virus 6 and multiple sclerosis: a Finnish twin study , 2008, Multiple sclerosis.

[27]  R. P. Mackay,et al.  Multiple Sclerosis in Twins and Their Relatives: Final Report , 1966 .

[28]  J. Kaprio,et al.  Genetic liability of type 1 diabetes and the onset age among 22,650 young Finnish twin pairs: a nationwide follow-up study. , 2003, Diabetes.

[29]  J. Kaprio,et al.  Multiple sclerosis in a nationwide series of twins , 1987, Neurology.

[30]  J. Hillert,et al.  Genetic association analysis of the interleukin 7 gene (IL7) in multiple sclerosis , 2007, Journal of Neuroimmunology.

[31]  A. Chinnaiyan,et al.  Identification of genes modulated in rheumatoid arthritis using complementary DNA microarray analysis of lymphoblastoid B cell lines from disease-discordant monozygotic twins. , 2006, Arthritis and rheumatism.

[32]  S. Di Giovanni,et al.  Multiple sclerosis in twins from continental Italy and Sardinia: A nationwide study , 2006, Annals of neurology.

[33]  J. Kaprio,et al.  Concordance and heritability of multiple sclerosis in Finland: study on a nationwide series of twins , 2008, European journal of neurology.

[34]  R. P. Mackay,et al.  Multiple sclerosis in twins and their relatives. , 1966, Archives of Neurology.

[35]  N. Risch,et al.  Twin concordance and sibling recurrence rates in multiple sclerosis , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[36]  J W Langston,et al.  Parkinson disease in twins: an etiologic study. , 1999, JAMA.