Journal Mobile Options
Table of Contents
Vol. 60, No. 1, 2005
Issue release date: 2005
Hum Hered 2005;60:1–9
(DOI:10.1159/000087135)

Complex Segregation Analysis of Obsessive-Compulsive Disorder in Families with Pediatric Probands

Hanna G.L.a · Fingerlin T.E.b · Himle J.A.a · Boehnke M.c
aDepartment of Psychiatry, University of Michigan Medical School, Ann Arbor, Mich., bDepartment of Preventive Medicine and Biometrics, University of Colorado Health Sciences Center, Denver, Colo. and cDepartment of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Mich., USA
email Corresponding Author

Abstract

Objective: The purpose of this study was to assess the mode of inheritance for obsessive-compulsive disorder (OCD) in families ascertained through pediatric probands. Methods: We ascertained 52 families (35 case and 17 control families) through probands between the ages of 10 and 17 years. Direct interviews were completed with 215 individuals. Family informant data were collected on another 450 individuals without direct interviews, forming two data sets with one contained within the other. Complex segregation analyses were performed using regressive models as programmed in REGTL in the S.A.G.E. package.All models used in the analyses included sex-specific age and type parameters. Results: All models that excluded a residual effect of an affected parent were rejected. With that parameter included, the environmental and sporadic models were rejected in comparisons with the most general model in both data sets (all p < 0.005). With the direct interview data, the general codominant Mendelian model was not rejected when compared with the most general model (p = 0.140). We could not distinguish between any of the simple Mendelian models using either data set. However, the dominant Mendelian model provided a somewhat better fit than the other Mendelian models to the direct interview data. Conclusions: The results provide evidence for a major susceptibility locus in families with OCD when age at onset is incorporated into the model. Mendelian factors at most partially explained the familial aggregation of the phenotype, and residual familial effects were necessary to fit the data adequately. The results support the importance of linkage efforts by suggesting that a major locus is segregating within a proportion of families with OCD ascertained through pediatric probands.


 goto top of outline Key Words

  • Obsessive-compulsive disorder
  • Complex segregation analysis
  • Regressive logistic models
  • Age at onset
  • Single major locus transmission

 goto top of outline Abstract

Objective: The purpose of this study was to assess the mode of inheritance for obsessive-compulsive disorder (OCD) in families ascertained through pediatric probands. Methods: We ascertained 52 families (35 case and 17 control families) through probands between the ages of 10 and 17 years. Direct interviews were completed with 215 individuals. Family informant data were collected on another 450 individuals without direct interviews, forming two data sets with one contained within the other. Complex segregation analyses were performed using regressive models as programmed in REGTL in the S.A.G.E. package.All models used in the analyses included sex-specific age and type parameters. Results: All models that excluded a residual effect of an affected parent were rejected. With that parameter included, the environmental and sporadic models were rejected in comparisons with the most general model in both data sets (all p < 0.005). With the direct interview data, the general codominant Mendelian model was not rejected when compared with the most general model (p = 0.140). We could not distinguish between any of the simple Mendelian models using either data set. However, the dominant Mendelian model provided a somewhat better fit than the other Mendelian models to the direct interview data. Conclusions: The results provide evidence for a major susceptibility locus in families with OCD when age at onset is incorporated into the model. Mendelian factors at most partially explained the familial aggregation of the phenotype, and residual familial effects were necessary to fit the data adequately. The results support the importance of linkage efforts by suggesting that a major locus is segregating within a proportion of families with OCD ascertained through pediatric probands.

Copyright © 2005 S. Karger AG, Basel


 goto top of outline References
  1. Zohar AH, Ratzoni G, Pauls DL, Apter A, Bleich A, Kron S, Rappaport M, Weizman A, Cohen DJ: An epidemiological study of obsessive-compulsive disorder and related disorders in Israeli adolescents. J Am Acad Child Adolesc Psychiatry 1992;31:1057–1061.
  2. Valleni-Basile LA, Garrison CZ, Jackson KL, Waller JL, McKeown RE, Addy CL, Cuffe SP: Frequency of obsessive-compulsive disorder in a community sample of young adolescents. J Am Acad Child Adolesc Psychiatry 1994;33:782–791.
  3. Weissman MM, Bland RC, Canino GJ, Greenwald S, Hwu HG, Lee CK, Newman SC, Oakley-Browne MA, Rubio-Stipec M, Wickramaratne PJ, Wittchen H-U, Yeh E-K: The cross national epidemiology of obsessive compulsive disorder. The Cross National Collaborative Group. J Clin Psychiatry 1994;55(suppl):5–10.

    External Resources

  4. Douglass HM, Moffitt TE, Dar R, McGee R, Silva P: Obsessive-compulsive disorder in a birth cohort of 18-year-olds: prevalence and predictors. J Am Acad Child Adolesc Psychiatry 1995;34:1424–1431.
  5. Burke KC, Burke JD Jr, Regier DA, Rae DS: Age at onset of selected mental disorders in five community populations. Arch Gen Psychiatry 1990;47:511–518.
  6. Hanna GL: Demographic and clinical features of obsessive-compulsive disorder in children and adolescents. J Am Acad Child Adolesc Psychiatry 1995;34:19–27.
  7. Nestadt G, Bienvenu OJ, Cai G, Samuels J, Eaton WW: Incidence of obsessive-compulsive disorder in adults. J Nerv Ment Dis 1998;186:401–406.
  8. Rosario-Campos MC, Leckman JF, Mercadante MT, Shavitt RG, Prado HS, Sada P, Zamignani D, Miguel EC: Adults with early-onset obsessive-compulsive disorder. Am J Psychiatry 2001;158:1899–1903.
  9. Geller D, Biederman J, Jones J, Park K, Schwartz S, Shapiro S, Coffey B: Is juvenile obsessive-compulsive disorder a developmental subtype of the disorder? A review of the pediatric literature. J Am Acad Child Adolesc Psychiatry 1998;37:420–427.
  10. Sobin C, Blundell ML, Karayiorgou M: Phenotypic differences in early- and late-onset obsessive-compulsive disorder. Comp Psychiatry 2000;41:373–379.
  11. Eichstedt JA, Arnold SL: Childhood-onset obsessive-compulsive disorder: A tic-related subtype of OCD? Clin Psychol Review 2001;21:137–158.
  12. Inouye E: Similar and dissimilar manifestations of obsessive-compulsive neurosis in monozygotic twins. Am J Psychiatry 1965;21:1171–1175.

    External Resources

  13. Carey G, Gottesman II: Twin and family studies of anxiety, phobic and obsessive disorders; in Klein DF, Rabkin J (eds): Anxiety: New Research and Changing Concepts. New York, Raven Press, 1981, pp 117–136.
  14. Clifford CA, Murray RM, Fulker DW: Genetic and environmental influences on obsessional traits and symptoms. Psychol Med 1984;14:791–800.
  15. Jonnal AH, Gardner GO, Prescott CA, Kendler KS: Obsessive and compulsive symptoms in a general population sample of female twins. Am J Med Genet Neuropsychiatr Genet 2000;96:791–796.
  16. Pauls DL, Alsobrook JP II, Goodman W, Rasmussen S, Leckman JF: A family study of obsessive-compulsive disorder. Am J Psychiatry 1995;152:76–84.
  17. Nestadt G, Samuels J, Riddle M, Bienvenu OJ III, Liang K-Y, LaBuda M, Walkup J, Grados M, Hoehn-Saric R: A family study of obsessive-compulsive disorder. Arch Gen Psychiatry 2000;57:358–363.
  18. Hanna GL, Himle JA, Curtis GC, Gillespie BW: A family study of obsessive-compulsive disorder with pediatric probands. Am J Med Genet Neuropsychiatr Genet 2005;134B:13–19.

    External Resources

  19. Nicolini H, Hanna GL, Baxter L, Schwartz J, Weissbecker K, Spence M: Segregation analysis of obsessive compulsive and associated disorders: Preliminary results. Ursus Medicus 1991;1:25–28.
  20. Cavallini MC, Bertelli S, Chiapparino D, Riboldi S, Bellodi L: Complex segregation analysis of obsessive-compulsive disorder in 141 families of eating disorder probands, with and without obsessive-compulsive disorder. Am J Med Genet 2000;96:384–391.
  21. Alsobrook JP II, Leckman JF, Goodman WK, Rasmussen SA, Pauls DL: Segregation analysis of obsessive-compulsive disorder using symptom-based factor scores. Am J Med Genet Neuropsychiatr Genet 1999;88:669–675.
  22. Nestadt G, Lan T, Samuels J, Riddle M, Bienvenu OJ III, Liang K-Y, Hoehn-Saric R, Cullen B, Grados M, Beaty TH, Shugart YY: Complex segregation analysis provides compelling evidence for a major gene underlying obsessive-compulsive disorder and for heterogeneity by sex. Am J Hum Genet 2000;67:1611–1616.
  23. Hanna GL, Veenstra-VanderWeele J, Cox NJ, Boehnke M, Himle JA, Curtis GC, Leventhal BL, Cook EH: Genome-wide linkage analysis of families with obsessive-compulsive disorder ascertained through pediatric probands. Am J Med Genet Neuropsychiatr Genet 2002;114:541–552.
  24. Willour VL, Shugart YY, Samuels J, Grados M, Cullen B, Bienvenu OJ III, Wang Y, Liang KY, Valle D, Hoehn-Saric R, Riddle M, Nestadt G: Replication study supports evidence for linkage to 9p24 in obsessive-compulsive disorder. Am J Hum Genet 2004;75:508–513.
  25. Lander E, Schork N: Genetic dissection of complex traits. Science 1994;265:2037–2048.
  26. American Psychiatric Association on Nomenclature and Statistics: Diagnostic and Statistical Manual of Mental Disorders, ed 3, revised. Washington, DC, American Psychiatric Association, 1987.
  27. Orvaschel H: Schedule for Affective Disorders and Schizophrenia for School Aged Children-Epidemiologic Version (K-SADS-E), Fourth Edition. Philadelphia, PA, Medical College of Pennsylvania, 1987.
  28. Spitzer RL, Williams JB, Gibbon M, First MB: Structured Clinical Interview for DSM-III-R (SCID). Washington, DC, American Psychiatric Press, 1990.
  29. Pauls DL, Hurst CR: Schedule for Tourette and Other Behavioral Syndromes. New Haven, CT, Child Study Center, Yale University, 1991.
  30. Goodman W, Price L, Rasmussen S, Mazure C, Fleischmann R, Hill C, Heninger G, Charney D: The Yale-Brown Obsessive Compulsive Scale: I. development, use, and reliability. Arch Gen Psychiatry 1989;46:1006–1011.
  31. Mannuza S, Fyer AJ, Endicott J, Klein DF: Family Informant Schedule and Criteria (FISC). New York, NY, Anxiety Disorders Clinic, New York Psychiatric Institute, 1985.
  32. Roy MA, Lanctot G, Merette C, Cliche D, Fournier JP, Boutin P, Rodrigue C, Charron L, Turgeon M, Hamel M, Montgrain N, Nicole L, Pires A, Wallot H, Ponton AM, Garneau Y, Dion C, Lavallee JC, Potvin A, Szatmari P, Maziade M: Clinical and methodological factors related to reliability of the best-estimate diagnostic procedure. Am J Psychiatry 1997;154:1726–1733.
  33. Cannings C, Thompson EA: Ascertainment in the sequential sampling of the pedigrees. Clin Genet 1977;12:208–212.
  34. Boehnke M, Young MR, Moll PP: Comparison of sequential and fixed-structure sampling of pedigrees in complex segregation analysis of a quantitative trait. Am J Hum Genet 1988;43:336–343.
  35. S.A.G.E. (Statistical Analysis for Genetic Epidemiology), version 3.1. Computer program package, available from the Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, 1997.
  36. Bonney GE: Regressive logistic models for family disease and other binary traits. Biometrics 1986;42:611–625.
  37. Elston R, George V: Age of onset, age at examination, and other covariates in the analysis of family data. Genet Epidemiol 1989;6:217–220.
  38. Khoury MJ, Beaty TH, Cohen BH: Fundamentals of Genetic Epidemiology. New York, Oxford University Press, 1993.
  39. Baer L: Factor analysis of symptom subtypes of obsessive compulsive disorder and their relation to personality and tic disorders. J Clin Psychiatry 1994;55:18–23.
  40. Leckman JF, Grice DE, Boardman, J, Zhang H, Vitale A, Bondi C, Alsobrook, J, Peterson BS, Cohen DJ, Rasmussen SA, Goodman WK, McDougle CJ, Pauls DL: Symptoms of obsessive compulsive disorder. Am J Psychiatry 1997;154:911–917.
  41. Summerfeldt LJ, Richter MA, Antony MM, Swinson RP: Symptom structure in obsessive-compulsive disorder: A confirmatory factor-analytic study. Behav Res Ther 1999;37:297–311.
  42. Mataix-Cols D, Rosario-Campos MC, Leckman JF: A multidimensional model of obsessive-compulsive disorder. Am J Psychiatry 2005;162:228–238.
  43. Zhang H, Leckman JF, Pauls DL, Tsai C-L, Kidd KK, Campos MR, the Tourette Syndrome Association International Consortium for Genetics: Genomewide scan of hoarding in sib pairs in which both sibs have Gilles de la Tourette Syndrome. Am J Hum Genet 2002;70:896–904.
  44. Leckman JF, Pauls DL, Zhang H, Rosario-Campos MC, Katsovich L, Kidd KK, Pakstis AJ, Alsobrook JP, Robertson MM, McMahon WM, Walkup JT, van de Wetering BJM, King RA, Cohen DJ, the Tourette Syndrome Association International Consortium for Genetics: Obsessive-compulsive symptom dimensions in affected sibling pairs diagnosed with Gilles de la Tourette Syndrome. Am J Med Genet Neuropsychiatr Genet 2003;116B:60–68.
  45. Cavallini MC, Albertazzi M, Bianchi L, Bellodi L: Anticipation of age at onset of obsessive-compulsive spectrum disorders in patients with obsessive-compulsive disorder. Psychiatry Res 2002;111:1–9.
  46. Walkup JT, LaBuda MC, Singer HS, Brown J, Riddle MA, Hurko O: Family study and segregation analysis of Tourette syndrome: Evidence for a mixed model of inheritance. Am J Hum Genet 1996;59:684–693.
  47. Grados MA, Riddle MA, Samuels JF, Liang K-Y, Hoehn-Saric R, Bienvenu OJ, Walkup JT, Song D, Nestadt G: The familial phenotype of obsessive-compulsive disorder in relation to tic disorders: the Hopkins OCD Family Study. Biol Psychiatry 2001;50:559–565.
  48. Bienvenu OJ, Samuels JF, Riddle MA, Hoehn-Saric R, Liang K-Y, Cullen BAM, Grados MA, Nestadt G: The relationship of obsessive-compulsive disorder to possible spectrum disorders: results from a family study. Biol Psychiatry 2000;48:287–293.
  49. Nestadt G, Samuels J, Riddle MA, Liang K-Y, Bienvenu OJ, Hoehn-Saric R, Grados M, Cullen B: The relationship between obsessive-compulsive disorder and anxiety and affective disorders: results from the Johns Hopkins OCD Family Study. Psychol Med 2001;31:481–487.
  50. Cavallini MC, Bertelli S, Chiapparino D, Riboldi S, Bellodi L: Complex segregation analysis of obsessive-compulsive disorder in 141 families of eating disorder probands, with and without obsessive-compulsive disorder. Am J Med Genet 2000;96:384–391.

 goto top of outline Author Contacts

Gregory L. Hanna, MD
Department of Psychiatry, University of Michigan Health System
2101 Commonwealth Boulevard, Suite C
Ann Arbor, MI 48109-0390 (USA)
Tel. +1 734 764 0234, Fax +1 734 936 8907, E-Mail ghanna@umich.edu


 goto top of outline Article Information

Received: December 23, 2004
Accepted after revision: May 12, 2005
Published online: July 27, 2005
Number of Print Pages : 9
Number of Figures : 2, Number of Tables : 1, Number of References : 50


 goto top of outline Publication Details

Human Heredity (International Journal of Human and Medical Genetics)

Vol. 60, No. 1, Year 2005 (Cover Date: 2005)

Journal Editor: Devoto, M. (Wilmington, Del.)
ISSN: 0001–5652 (print), 1423–0062 (Online)

For additional information: http://www.karger.com/hhe


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

Objective: The purpose of this study was to assess the mode of inheritance for obsessive-compulsive disorder (OCD) in families ascertained through pediatric probands. Methods: We ascertained 52 families (35 case and 17 control families) through probands between the ages of 10 and 17 years. Direct interviews were completed with 215 individuals. Family informant data were collected on another 450 individuals without direct interviews, forming two data sets with one contained within the other. Complex segregation analyses were performed using regressive models as programmed in REGTL in the S.A.G.E. package.All models used in the analyses included sex-specific age and type parameters. Results: All models that excluded a residual effect of an affected parent were rejected. With that parameter included, the environmental and sporadic models were rejected in comparisons with the most general model in both data sets (all p < 0.005). With the direct interview data, the general codominant Mendelian model was not rejected when compared with the most general model (p = 0.140). We could not distinguish between any of the simple Mendelian models using either data set. However, the dominant Mendelian model provided a somewhat better fit than the other Mendelian models to the direct interview data. Conclusions: The results provide evidence for a major susceptibility locus in families with OCD when age at onset is incorporated into the model. Mendelian factors at most partially explained the familial aggregation of the phenotype, and residual familial effects were necessary to fit the data adequately. The results support the importance of linkage efforts by suggesting that a major locus is segregating within a proportion of families with OCD ascertained through pediatric probands.



 goto top of outline Author Contacts

Gregory L. Hanna, MD
Department of Psychiatry, University of Michigan Health System
2101 Commonwealth Boulevard, Suite C
Ann Arbor, MI 48109-0390 (USA)
Tel. +1 734 764 0234, Fax +1 734 936 8907, E-Mail ghanna@umich.edu


 goto top of outline Article Information

Received: December 23, 2004
Accepted after revision: May 12, 2005
Published online: July 27, 2005
Number of Print Pages : 9
Number of Figures : 2, Number of Tables : 1, Number of References : 50


 goto top of outline Publication Details

Human Heredity (International Journal of Human and Medical Genetics)

Vol. 60, No. 1, Year 2005 (Cover Date: 2005)

Journal Editor: Devoto, M. (Wilmington, Del.)
ISSN: 0001–5652 (print), 1423–0062 (Online)

For additional information: http://www.karger.com/hhe


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Zohar AH, Ratzoni G, Pauls DL, Apter A, Bleich A, Kron S, Rappaport M, Weizman A, Cohen DJ: An epidemiological study of obsessive-compulsive disorder and related disorders in Israeli adolescents. J Am Acad Child Adolesc Psychiatry 1992;31:1057–1061.
  2. Valleni-Basile LA, Garrison CZ, Jackson KL, Waller JL, McKeown RE, Addy CL, Cuffe SP: Frequency of obsessive-compulsive disorder in a community sample of young adolescents. J Am Acad Child Adolesc Psychiatry 1994;33:782–791.
  3. Weissman MM, Bland RC, Canino GJ, Greenwald S, Hwu HG, Lee CK, Newman SC, Oakley-Browne MA, Rubio-Stipec M, Wickramaratne PJ, Wittchen H-U, Yeh E-K: The cross national epidemiology of obsessive compulsive disorder. The Cross National Collaborative Group. J Clin Psychiatry 1994;55(suppl):5–10.

    External Resources

  4. Douglass HM, Moffitt TE, Dar R, McGee R, Silva P: Obsessive-compulsive disorder in a birth cohort of 18-year-olds: prevalence and predictors. J Am Acad Child Adolesc Psychiatry 1995;34:1424–1431.
  5. Burke KC, Burke JD Jr, Regier DA, Rae DS: Age at onset of selected mental disorders in five community populations. Arch Gen Psychiatry 1990;47:511–518.
  6. Hanna GL: Demographic and clinical features of obsessive-compulsive disorder in children and adolescents. J Am Acad Child Adolesc Psychiatry 1995;34:19–27.
  7. Nestadt G, Bienvenu OJ, Cai G, Samuels J, Eaton WW: Incidence of obsessive-compulsive disorder in adults. J Nerv Ment Dis 1998;186:401–406.
  8. Rosario-Campos MC, Leckman JF, Mercadante MT, Shavitt RG, Prado HS, Sada P, Zamignani D, Miguel EC: Adults with early-onset obsessive-compulsive disorder. Am J Psychiatry 2001;158:1899–1903.
  9. Geller D, Biederman J, Jones J, Park K, Schwartz S, Shapiro S, Coffey B: Is juvenile obsessive-compulsive disorder a developmental subtype of the disorder? A review of the pediatric literature. J Am Acad Child Adolesc Psychiatry 1998;37:420–427.
  10. Sobin C, Blundell ML, Karayiorgou M: Phenotypic differences in early- and late-onset obsessive-compulsive disorder. Comp Psychiatry 2000;41:373–379.
  11. Eichstedt JA, Arnold SL: Childhood-onset obsessive-compulsive disorder: A tic-related subtype of OCD? Clin Psychol Review 2001;21:137–158.
  12. Inouye E: Similar and dissimilar manifestations of obsessive-compulsive neurosis in monozygotic twins. Am J Psychiatry 1965;21:1171–1175.

    External Resources

  13. Carey G, Gottesman II: Twin and family studies of anxiety, phobic and obsessive disorders; in Klein DF, Rabkin J (eds): Anxiety: New Research and Changing Concepts. New York, Raven Press, 1981, pp 117–136.
  14. Clifford CA, Murray RM, Fulker DW: Genetic and environmental influences on obsessional traits and symptoms. Psychol Med 1984;14:791–800.
  15. Jonnal AH, Gardner GO, Prescott CA, Kendler KS: Obsessive and compulsive symptoms in a general population sample of female twins. Am J Med Genet Neuropsychiatr Genet 2000;96:791–796.
  16. Pauls DL, Alsobrook JP II, Goodman W, Rasmussen S, Leckman JF: A family study of obsessive-compulsive disorder. Am J Psychiatry 1995;152:76–84.
  17. Nestadt G, Samuels J, Riddle M, Bienvenu OJ III, Liang K-Y, LaBuda M, Walkup J, Grados M, Hoehn-Saric R: A family study of obsessive-compulsive disorder. Arch Gen Psychiatry 2000;57:358–363.
  18. Hanna GL, Himle JA, Curtis GC, Gillespie BW: A family study of obsessive-compulsive disorder with pediatric probands. Am J Med Genet Neuropsychiatr Genet 2005;134B:13–19.

    External Resources

  19. Nicolini H, Hanna GL, Baxter L, Schwartz J, Weissbecker K, Spence M: Segregation analysis of obsessive compulsive and associated disorders: Preliminary results. Ursus Medicus 1991;1:25–28.
  20. Cavallini MC, Bertelli S, Chiapparino D, Riboldi S, Bellodi L: Complex segregation analysis of obsessive-compulsive disorder in 141 families of eating disorder probands, with and without obsessive-compulsive disorder. Am J Med Genet 2000;96:384–391.
  21. Alsobrook JP II, Leckman JF, Goodman WK, Rasmussen SA, Pauls DL: Segregation analysis of obsessive-compulsive disorder using symptom-based factor scores. Am J Med Genet Neuropsychiatr Genet 1999;88:669–675.
  22. Nestadt G, Lan T, Samuels J, Riddle M, Bienvenu OJ III, Liang K-Y, Hoehn-Saric R, Cullen B, Grados M, Beaty TH, Shugart YY: Complex segregation analysis provides compelling evidence for a major gene underlying obsessive-compulsive disorder and for heterogeneity by sex. Am J Hum Genet 2000;67:1611–1616.
  23. Hanna GL, Veenstra-VanderWeele J, Cox NJ, Boehnke M, Himle JA, Curtis GC, Leventhal BL, Cook EH: Genome-wide linkage analysis of families with obsessive-compulsive disorder ascertained through pediatric probands. Am J Med Genet Neuropsychiatr Genet 2002;114:541–552.
  24. Willour VL, Shugart YY, Samuels J, Grados M, Cullen B, Bienvenu OJ III, Wang Y, Liang KY, Valle D, Hoehn-Saric R, Riddle M, Nestadt G: Replication study supports evidence for linkage to 9p24 in obsessive-compulsive disorder. Am J Hum Genet 2004;75:508–513.
  25. Lander E, Schork N: Genetic dissection of complex traits. Science 1994;265:2037–2048.
  26. American Psychiatric Association on Nomenclature and Statistics: Diagnostic and Statistical Manual of Mental Disorders, ed 3, revised. Washington, DC, American Psychiatric Association, 1987.
  27. Orvaschel H: Schedule for Affective Disorders and Schizophrenia for School Aged Children-Epidemiologic Version (K-SADS-E), Fourth Edition. Philadelphia, PA, Medical College of Pennsylvania, 1987.
  28. Spitzer RL, Williams JB, Gibbon M, First MB: Structured Clinical Interview for DSM-III-R (SCID). Washington, DC, American Psychiatric Press, 1990.
  29. Pauls DL, Hurst CR: Schedule for Tourette and Other Behavioral Syndromes. New Haven, CT, Child Study Center, Yale University, 1991.
  30. Goodman W, Price L, Rasmussen S, Mazure C, Fleischmann R, Hill C, Heninger G, Charney D: The Yale-Brown Obsessive Compulsive Scale: I. development, use, and reliability. Arch Gen Psychiatry 1989;46:1006–1011.
  31. Mannuza S, Fyer AJ, Endicott J, Klein DF: Family Informant Schedule and Criteria (FISC). New York, NY, Anxiety Disorders Clinic, New York Psychiatric Institute, 1985.
  32. Roy MA, Lanctot G, Merette C, Cliche D, Fournier JP, Boutin P, Rodrigue C, Charron L, Turgeon M, Hamel M, Montgrain N, Nicole L, Pires A, Wallot H, Ponton AM, Garneau Y, Dion C, Lavallee JC, Potvin A, Szatmari P, Maziade M: Clinical and methodological factors related to reliability of the best-estimate diagnostic procedure. Am J Psychiatry 1997;154:1726–1733.
  33. Cannings C, Thompson EA: Ascertainment in the sequential sampling of the pedigrees. Clin Genet 1977;12:208–212.
  34. Boehnke M, Young MR, Moll PP: Comparison of sequential and fixed-structure sampling of pedigrees in complex segregation analysis of a quantitative trait. Am J Hum Genet 1988;43:336–343.
  35. S.A.G.E. (Statistical Analysis for Genetic Epidemiology), version 3.1. Computer program package, available from the Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, 1997.
  36. Bonney GE: Regressive logistic models for family disease and other binary traits. Biometrics 1986;42:611–625.
  37. Elston R, George V: Age of onset, age at examination, and other covariates in the analysis of family data. Genet Epidemiol 1989;6:217–220.
  38. Khoury MJ, Beaty TH, Cohen BH: Fundamentals of Genetic Epidemiology. New York, Oxford University Press, 1993.
  39. Baer L: Factor analysis of symptom subtypes of obsessive compulsive disorder and their relation to personality and tic disorders. J Clin Psychiatry 1994;55:18–23.
  40. Leckman JF, Grice DE, Boardman, J, Zhang H, Vitale A, Bondi C, Alsobrook, J, Peterson BS, Cohen DJ, Rasmussen SA, Goodman WK, McDougle CJ, Pauls DL: Symptoms of obsessive compulsive disorder. Am J Psychiatry 1997;154:911–917.
  41. Summerfeldt LJ, Richter MA, Antony MM, Swinson RP: Symptom structure in obsessive-compulsive disorder: A confirmatory factor-analytic study. Behav Res Ther 1999;37:297–311.
  42. Mataix-Cols D, Rosario-Campos MC, Leckman JF: A multidimensional model of obsessive-compulsive disorder. Am J Psychiatry 2005;162:228–238.
  43. Zhang H, Leckman JF, Pauls DL, Tsai C-L, Kidd KK, Campos MR, the Tourette Syndrome Association International Consortium for Genetics: Genomewide scan of hoarding in sib pairs in which both sibs have Gilles de la Tourette Syndrome. Am J Hum Genet 2002;70:896–904.
  44. Leckman JF, Pauls DL, Zhang H, Rosario-Campos MC, Katsovich L, Kidd KK, Pakstis AJ, Alsobrook JP, Robertson MM, McMahon WM, Walkup JT, van de Wetering BJM, King RA, Cohen DJ, the Tourette Syndrome Association International Consortium for Genetics: Obsessive-compulsive symptom dimensions in affected sibling pairs diagnosed with Gilles de la Tourette Syndrome. Am J Med Genet Neuropsychiatr Genet 2003;116B:60–68.
  45. Cavallini MC, Albertazzi M, Bianchi L, Bellodi L: Anticipation of age at onset of obsessive-compulsive spectrum disorders in patients with obsessive-compulsive disorder. Psychiatry Res 2002;111:1–9.
  46. Walkup JT, LaBuda MC, Singer HS, Brown J, Riddle MA, Hurko O: Family study and segregation analysis of Tourette syndrome: Evidence for a mixed model of inheritance. Am J Hum Genet 1996;59:684–693.
  47. Grados MA, Riddle MA, Samuels JF, Liang K-Y, Hoehn-Saric R, Bienvenu OJ, Walkup JT, Song D, Nestadt G: The familial phenotype of obsessive-compulsive disorder in relation to tic disorders: the Hopkins OCD Family Study. Biol Psychiatry 2001;50:559–565.
  48. Bienvenu OJ, Samuels JF, Riddle MA, Hoehn-Saric R, Liang K-Y, Cullen BAM, Grados MA, Nestadt G: The relationship of obsessive-compulsive disorder to possible spectrum disorders: results from a family study. Biol Psychiatry 2000;48:287–293.
  49. Nestadt G, Samuels J, Riddle MA, Liang K-Y, Bienvenu OJ, Hoehn-Saric R, Grados M, Cullen B: The relationship between obsessive-compulsive disorder and anxiety and affective disorders: results from the Johns Hopkins OCD Family Study. Psychol Med 2001;31:481–487.
  50. Cavallini MC, Bertelli S, Chiapparino D, Riboldi S, Bellodi L: Complex segregation analysis of obsessive-compulsive disorder in 141 families of eating disorder probands, with and without obsessive-compulsive disorder. Am J Med Genet 2000;96:384–391.