Twin Pair Resemblance for Psychiatric Hospitalization in the Swedish Twin Registry: A 32-year Follow-up Study of 29,602 Twin Pairs

Abstract

Background

Allgulander et al. (Allgulander C, Nowak J, Rice JP (1991) Acta Psychiatr Scand 83, 12) published twin pair analyses of psychiatric hospitalization for like-sex pairs from the Swedish Twin Registry born 1926–1958. As noted in a subsequent letter (Allgulander C, Nowak J, Rice JP (1992) Acta Psychiatr Scand 86, 421), several features of the original study resulted in under-ascertainment of cases and underestimated heritability, particularly for alcoholism. The present report updates the prior results by using 17 additional years of follow-up, including members of opposite-sex twin pairs, and addressing biases arising from cohort effects and from excluding pairs with unknown zygosity.

Methods

Registry records for 29,602 twin pairs born 1926–1958 were matched against national databases of psychiatric and medical hospitalizations from 1972–2000 to obtain ICD diagnostic codes. Zygosity was known for 10,903 opposite-sex pairs and 15,401 like-sex pairs who participated previously in research. Twin-pair resemblance and genetic and environmental variance proportions were estimated for hospitalization for alcoholism, affective disorders, psychosis, and (in females) anxiety disorders.

Results

Hospitalization rates during the ascertainment window were: alcoholism: males = 3.67%, females = 0.94%; affective disorders: males = 1.99%, females = 2.75%; anxiety disorders: males = 0.46%, females = 0.74%; and psychotic disorders: males = 1.70%, females = 1.96%. Twins from like-sex pairs with unknown zygosity had significantly higher prevalences than those with known zygosity. Tetrachoric correlations and heritability estimates were affected by the method used to model unknown zygosity and cohort effects.

Conclusions

Inclusion of additional follow-up information, opposite-sex twin pairs, age-adjustment, and use of current ICD definitions yielded higher heritability estimates for alcoholism, anxiety disorders, and psychosis than previously published for this nationally-representative sample of twins from Sweden. The results show that relatively small selection biases can alter twin study results and underscore the importance of addressing under-ascertainment of cases in genetic research based on volunteers.

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Notes

  1. 1.

    The disorders and ICD codes corresponding to each diagnostic category were as follows: Alcoholism: alcohol dependence, alcohol abuse, alcohol-induced psychosis (ICD-7: 307,322; ICD-8: 291,303; ICD-9: 291,303,305.0); Anxiety Disorders: anxiety reaction, anxiety neurosis, phobic reaction, phobic neurosis, obsessive-compulsive reaction, obsessive-compulsive neurosis (ICD-7: 310,312,313; ICD-8 & ICD-9: 300.0, 300.2, 300.3); Affective Disorders: depressive neurosis, affective personality disorder, depressive disorder, affective psychosis (ICD-7: 301302314; ICD-8: 296,300.4,301.1; ICD-9: 296,300.4,301.1,311); Psychosis: schizophrenia, affective psychosis, acute psychosis, unspecified psychosis, paranoia (ICD-7: 300-303,309; ICD-8 & 9: 295-299); Substance Abuse: drug dependence, drug abuse, drug-induced psychosis (ICD-7: 323; ICD-8: 294.3, 304; ICD-9: 292, 304, 305.2-305.9).

  2. 2.

    In preliminary analyses, the bootstrapping was also done under an assumption of a 50:50 MZ:DZ ratio among unknown pairs. The results were essentially identical to those obtained using sample-based proportions, which is not surprising given the very low prevalences being studied. Based on the correlations from each bootstrapped data set, we calculated genetic and environmental parameters based on algebraic expectations. That is, within each sex, h= 2*(rMZ−rDZ), c= rMZ−h2, e= 1−(h+ c2), with the additional restrictions of h2 ≥ 0 and c2 ≥ 0 (i.e., if rDZ > rMZ for a sample, h2 was set to 0 and c2 was fixed to the weighted average of rMZ and rDZ). These calculations are based on the same expectations as a structural model analysis, and yield the same results under the conditions of a saturated model and approximately equal group sizes. We used this method for convenience as all the calculations could be done using a SAS macro rather than transferring the 1,000 data sets into another program. Based on the bootstrapping analyses, we obtained 1,000 sets of the four like-sex pair correlations and six parameter estimates (a2, c2, and e2 for males and females). The datasets for males and females were independent. Doing all possible combinations of each male dataset with each female dataset would have meant 1,000,000 runs and was unnecessary, because the male and female bootstraps were independent and we were using a saturated model (i.e., there was no dependence between the male and female parameter estimates). Within each sex, there is nearly complete dependence between the MZ and DZ correlations (e.g., across the 1,000 runs, the correlation of the rMZ and rDZ estimates is r = −0.98). Thus, the upper and lower bounds of the confidence intervals for the parameters considered individually are virtually identical (±0.01) to the upper and lower bounds for the joint distribution of h2 and c2.

References

  1. Allgulander C, Nowak J, Rice JP (1991) Psychopathology and treatment of 30,334 twins in Sweden: II. Heritability estimates of psychiatric diagnosis and treatment in 12,884 twin pairs. Acta Psychiatr Scand 83:12–15

    PubMed  CAS  Google Scholar 

  2. Allgulander C, Nowak J, Rice JP (1992) Psychopathology and treatment of 30,334 twins in Sweden (Letter). Acta Psychiatr Scand 86:421–422

    PubMed  CAS  Google Scholar 

  3. Bohman M, Sigvardsson S, Cloninger CR (1981) Maternal inheritance of alcohol abuse. Cross-fostering analysis of adopted women. Arch Gen Psychiatry 38:965–969

    PubMed  CAS  Google Scholar 

  4. Cardno AG, Gottesman II (2000) Twin studies of schizophrenia from bow-and-arrow concordances to star wars Mx and functional genomics. Am J Med Genet 97:12–17

    PubMed  Article  CAS  Google Scholar 

  5. Cloninger CR, Bohman M, Sigvardsson S (1981) Inheritance of alcohol abuse. Cross-fostering analysis of adopted men. Arch Gen Psychiatry 38:861–868

    PubMed  CAS  Google Scholar 

  6. Eley TC, Collier D, McGuffin P (2002) Anxiety and eating disorders. In: McGuffin P, Owen MJ, Gottesman II (eds) Psychiatric genetics and genomics. Oxford University Press, London, pp 303–340

    Google Scholar 

  7. Falconer DS (1965) The inheritance of liability to certain diseases, estimated from the incidence among relatives. Ann Hum Genet 29:51–76

    Google Scholar 

  8. Foley DL, Neale MC, Kendler KS (1998) Reliability of a lifetime history of major depression: implications for heritability and comorbidity. Psychol Med 28:857–870

    PubMed  Article  CAS  Google Scholar 

  9. Heath AC, Nyholt DR, Neuman R, Madden PA, Bucholz KK, Todd RD, Nelson EC, Montgomery GW, Martin NG (2003) Zygosity diagnosis in the absence of genotypic data: an approach using latent class analysis. Twin Res 6:22–26

    PubMed  Article  Google Scholar 

  10. Jones I, Kent L, Craddock N (2002) Genetic of affective disorders. In: McGuffin P, Owen MJ, Gottesman II (eds) Psychiatric genetics and genomics. Oxford University Press, London, pp 211–245

    Google Scholar 

  11. Kaij L (1960) Alcoholism in twins. Almqvist and Wiksell, Stockholm

    Google Scholar 

  12. Kendler KS, Holm NV (1985) Differential enrollment in twin registries: its effect on prevalence and concordance rates and estimates of genetic parameters. Acta Genetica Medica et Gemellologia 34:125–140

    CAS  Google Scholar 

  13. Kendler KS, Pedersen NC, Neale MC, Mathe AA (1995) A pilot Swedish twin study of affective illness including hospital- and population-ascertained subsamples: results of model fitting. Behav Genet 25:217–232

    PubMed  Article  CAS  Google Scholar 

  14. Kendler KS, Prescott CA, Neale MC, Pedersen NL (1997) Temperance board registration for alcohol abuse in a national sample of Swedish male twins, born 1902 to 1949. Arch Gen Psychiatry 54:178–184

    PubMed  CAS  Google Scholar 

  15. Kessler RC, McGonagle KA, Zhao S, Nelson CB, Hughes M, Eshleman S, Wittchen H-U, Kendler KS (1994) Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States: results from the National Comorbidity Survey. Arch Gen Psychiatry 51:8–10

    PubMed  CAS  Google Scholar 

  16. Lichtenstein P, deFaire U, Floderus B, Svartengren M, Svedberg P, Pedersen NL (2002) The Swedish twin registry: a unique resource for clinical, epidemiological and genetic studies. J Intern Med 252:184–205

    PubMed  Article  CAS  Google Scholar 

  17. Maes HH, Neale MC, Kendler KS, Hewitt JK, Silberg JL, Foley DL, Meyer JM, Rutter M, Simonoff E, Pickles A, Eaves LJ (1998) Assortative mating for major psychiatric diagnoses in two population-based samples. Psychol Med 28:1389–1401

    PubMed  Article  CAS  Google Scholar 

  18. McGuffin P, Katz R, Watkins S, Rutherford J (1996) A hospital based twin register of the heritability of DSM-IV unipolar depression. Arch Gen Psychiatry 53:129–136

    PubMed  CAS  Google Scholar 

  19. Medlund P, Cederlof R, Floderus-Myrhed B, Friberg L, Sorensen SA (1976) A new Swedish twin registry containing environmental and medical base line data from about 14,000 same-sexed pairs born 1926–58. Acta Med Scand Suppl. 600, 1–111

    Google Scholar 

  20. Merikangas KR, Mehta RL, Molnar BE, Walters EE, Swendsen JD, Aguilar-Gaziola S, Bijl R, Borges G, Caraveo-Anduaga JJ, DeWit DJ, Kolody B, Vega WA, Wittchen H-U, Kessler RC (1998) Comorbidity of substance use disorders with mood and anxiety disorders: results of the international consortium in psychiatric epidemiology. Addict Behav 23:893–907

    PubMed  Article  CAS  Google Scholar 

  21. Muthen LK, Muthen BO (2003) Mplus user’s guide. Version 3.0. Muthen & Muthen., Los Angeles, CA

    Google Scholar 

  22. Neale MC (2003) A finite mixture distribution model for data collected from twins. Twin Res 6:235–239

    PubMed  Article  Google Scholar 

  23. Owen MJ, O’Donovan MC, Gottesman II (2002) Schizophrenia. In: McGuffin P, Owen MJ, Gottesman II (eds) Psychiatric genetics and genomics. Oxford University Press, London, pp 247–266

    Google Scholar 

  24. Pedersen NL, Lichtenstein P, Svedberg P (2002) The Swedish twin registry in the third millenium. Twin Res 5:427–432

    PubMed  Article  Google Scholar 

  25. Prescott CA (2003) Alcoholism and drug addiction. Encyclopedia of the human genome. Nature Publishing Group, London. (http://www.ehgonline.net)

  26. Prescott CA (2004). Using the Mplus computer program to estimate models for continuous and categorical data from twins. Behav Genet 34:7–40

    Article  Google Scholar 

  27. Prescott CA, Kendler KS (2000) Influence of ascertainment strategy on finding sex differences in genetic influences from twin studies of alcoholism. Neuropsychiatric Genetics 96:754–761

    PubMed  Article  CAS  Google Scholar 

  28. Reed T, Page WF, Viken RJ, Christian JC (1996) Genetic predisposition to organ-specific endpoints of alcoholism. Alcohol Clin Exp Res 20:1528–1533

    PubMed  Article  CAS  Google Scholar 

  29. Rose RJ, Kaprio J, Williams CJ, Viken R, Obremski K (1990) Social contact and sibling similarity: facts, issues, and red herrings. Behav Genet 20:763–778

    PubMed  Article  CAS  Google Scholar 

  30. Soldani F, Sullivan PF, Pedersen NL (2005) Mania in the Swedish twin registry: criterion validity and prevalence. Aust N Z J Psychiatry 39:235–243

    PubMed  Article  Google Scholar 

  31. Sullivan PF, Kendler KS, Neale MC (2003) Schizophrenia as a complex trait: evidence from a meta-analysis of twin studies. Arch Gen Psychiatry 60:1187–1192

    PubMed  Article  Google Scholar 

  32. Sullivan PF, Neale MC, Kendler KS (2000) Genetic epidemiology of major depression: review and meta analysis. Am J Psychiatry 157:1552–1562

    PubMed  Article  CAS  Google Scholar 

  33. True WR, Heath AC, Bucholz K, Slutske W, Romels JC, Scherrer JF, Lin N, Eisen SA, Goldberg J, Lyons M, Tsuang MT (1996) Models of treatment seeking for alcoholism: the role of genes and environment. Alcohol Clin Exp Res 20:1577–1581

    PubMed  Article  CAS  Google Scholar 

  34. World Health Organization (1960) International classification of diseases––seventh revision. World Health Organization, Geneva

    Google Scholar 

  35. World Health Organization (1968) International classification of diseases, eighth revision. World Health Organization, Geneva

    Google Scholar 

  36. World Health Organization (1978) International classification of diseases, ninth revision. World Health Organization, Geneva

    Google Scholar 

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Acknowledgments

The Swedish Twin Registry is supported by grants from the Swedish Scientific Council, the Swedish Ministry of Higher Education, and Astra Zeneca. The authors are grateful to Lisa Halberstadt for helpful comments and J. J. McArdle for statistical advice. Preparation of this manuscript was supported by grants R01-AA-11408 and K01-AA-00236 from the U.S. National Institutes of Health and an Independent Investigator award from the National Alliance for Research on Schizophrenia and Affective Disorders (to CAP). Rebecca Ortiz assisted with manuscript preparation.

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Correspondence to Carol A. Prescott.

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Prescott, C.A., Kuhn, J.W. & Pedersen, N.L. Twin Pair Resemblance for Psychiatric Hospitalization in the Swedish Twin Registry: A 32-year Follow-up Study of 29,602 Twin Pairs. Behav Genet 37, 547–558 (2007). https://doi.org/10.1007/s10519-007-9143-6

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Keywords

  • Alcoholism
  • Depression
  • Psychosis
  • Anxiety
  • Ascertainment