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Table of Contents
Vol. 59, No. 3, 2005
Issue release date: June 2005
Section title: Original Paper
Hum Hered 2005;59:136–143
(DOI:10.1159/000085572)

Developmental Dyslexia – Recurrence Risk Estimates from a German Bi-Center Study Using the Single Proband Sib Pair Design

Ziegler A.a · König I.R.a · Deimel W.b · Plume E.c · Nöthen M.M.d · Propping P.d · Kleensang A.a · Müller-Myhsok B.e · Warnke A.c · Remschmidt H.b · Schulte-Körne G.b
aInstitut für Medizinische Biometrie und Statistik, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Universität zu Lübeck, Lübeck, bKlinik für Psychiatrie und Psychotherapie des Kindes- und Jugendalters, Philipps-Universität Marburg, Marburg, cKlinik und Poliklinik für Kinder- und Jugendpsychiatrie, Julius-Maximilians-Universität Würzburg, Würzburg, dInstitut für Humangenetik, Universität Bonn, Bonn, and eMax-Planck-Institut für Psychiatrie München, München, Germany
email Corresponding Author

Abstract

Objective: Several studies have demonstrated a genetic component for dyslexia. However, both segregation and linkage analyses show contradictory results pointing at the necessity of an optimal ascertainment scheme for molecular genetic studies. Previously, we have argued that the single proband sib pair design (SPSP) would be optimal. The aims of this paper therefore are to demonstrate the practicability of the SPSP design and the estimation of recurrence risks for reading and writing. Methods: We assessed spelling and reading in a family sample ascertained through the SPSP design. 287 families with at least two siblings and their parents were recruited. At least one child was affected with spelling disorder according to a one standard deviation (1SD) discrepancy criterion. Results: Mean values for probands and their siblings were different for both the spelling and the reading phenotype. For the probands, variances of the phenotype spelling were smaller. These effects became stronger with more extreme selection criteria. Both siblings fulfilled the 1SD criterion for spelling and reading in 60.3 and 28.9% of the families, respectively, indicating a low cost efficiency of the double proband sib pair approach. A recurrence risk of 4.52 (CI: 4.07–4.93) was obtained for spelling when the 1SD criterion was applied to both siblings. Recurrence risk estimates were similar for reading. Conclusion: The study demonstrates the suitability of the SPSP design for genetic analysis of dyslexia. The recurrence risk estimates may be used for determining sample sizes in gene mapping studies.

© 2005 S. Karger AG, Basel


  

Key Words

  • Dyslexia
  • Genetics
  • Reading disability
  • Recurrence risk
  • Risch’s lambda
  • Single proband sib pair design

References

  1. Francks C, MacPhie IL, Monaco AP: The genetic basis of dyslexia. Lancet Neurol 2002;1:483–490.
  2. Schulte-Körne G: Annotation: Genetics of reading and spelling disorder. J Child Psychol Psychiatry 2001;42:985–997.
  3. Francks C, Fisher SE, Olson RK, Pennington BF, Smith SD, DeFries JC, Monaco AP: Fine mapping of the chromosome 2p12–16 dyslexia susceptibility locus: quantitative association analysis and positional candidate genes SEMA4F and OTX1. Psychiatr Genet 2002;12:35–41.
  4. Schulte-Körne G: Legasthenie und Sprachwahrnehmung. Münster, Waxmann, 2001.
  5. Lewitter FI, DeFries JC, Elston RC: Genetic models of reading disability. Behav Genet 1980;10:9–30.
  6. Pennington BF, Gilger JW, Pauls D, Smith SA, Smith SD, DeFries JC: Evidence for major gene transmission of developmental dyslexia. J Am Med Assoc 1991;266:1527–1534.
  7. Chapman NH, Raskind WH, Thomson JB, Berninger VW, Wijsman EM: Segregation analysis of phenotypic components of learning disabilities. II. Phonological decoding. Am J Med Genet 2003;121B:60–70.
  8. Wijsman EM, Peterson D, Leutenegger AL, Thomson JB, Goddard KA, Hsu L, Berninger VW, Raskind WH: Segregation analysis of phenotypic components of learning disabilities. I. Nonword memory and digit span. Am J Hum Genet 2000;67:631–646.
  9. Gilger JW, Borecki IB, DeFries JC, Pennington BF: Commingling and segregation analysis of reading performance in families of normal reading probands. Behav Genet 1994;24:345–355.
  10. Lewis BA, Cox NJ, Byard PJ: Segregation analysis of speech and language disorders. Behav Genet 1993;23:291–297.
  11. Ziegler A, Hebebrand J: Sample size calculations for linkage analysis using extreme sib pairs based on segregation analysis with the quantitative phenotype body weight as an example. Genet Epidemiol 1998;15:577–593.
  12. Grigorenko EL, Wood FB, Meyer MS, Pauls JE, Hart LA, Pauls DL: Linkage studies suggest a possible locus for developmental dyslexia on chromosome 1p. Am J Med Genet 2001;105:120–129.
  13. Rabin M, Wen XL, Hepburn M, Lubs HA, Feldman E, Duara R: Suggestive linkage of developmental dyslexia to chromosome 1p34-p36. Lancet 1993;342:178.
  14. Kaminen N, Hannula-Jouppi K, Kestila M, Lahermo P, Muller K, Kaaranen M, Myllyluoma B, Voutilainen A, Lyytinen H, Nopola-Hemmi J, Kere J: A genome scan for developmental dyslexia confirms linkage to chromosome 2p11 and suggests a new locus on 7q32. J Med Genet 2003;40:340–345.
  15. Grigorenko EL, Wood FB, Meyer MS, Hart LA, Speed WC, Shuster A, Pauls DL: Susceptibility loci for distinct components of developmental dyslexia on chromosomes 6 and 15. Am J Hum Genet 1997;60:27–39.
  16. Kaplan DE, Gayan J, Ahn J, Won TW, Pauls D, Olson RK, DeFries JC, Wood F, Pennington BF, Page GP, Smith SD, Gruen JR: Evidence for linkage and association with reading disability on 6p21.3–22. Am J Hum Genet 2002;70:1287–1298.
  17. Schulte-Körne G, Grimm T, Nöthen MM, Müller-Myhsok B, Cichon S, Vogt IR, Propping P, Remschmidt H: Evidence for linkage of spelling disability to chromosome 15. Am J Hum Genet 1998;63:279–282.
  18. Fisher SE, Francks C, Marlow AJ, MacPhie IL, Newbury DF, Cardon LR, Ishikawa-Brush Y, Richardson AJ, Talcott JB, Gayán J, Olson RK, Pennington BF, Smith SD, DeFries JC, Stein JF, Monaco AP: Independent genome-wide scans identify a chromosome 18 quantitative-trait locus influencing dyslexia. Nat Genet 2001;17:17.
  19. Cardon LR, Smith SD, Fulker DW, Kimberling WJ, Pennington BF, DeFries JC: Quantitative trait locus for reading disability on chromosome 6. Science 1994;266:276–279.
  20. Field LL, Kaplan BJ: Absence of linkage of phonological coding dyslexia to chromosome 6p23-p21.3 in a large family data set. Am J Hum Genet 1998;63:1448–1456.
  21. Petryshen TL, Kaplan BJ, Fu Liu M, de French NS, Tobias R, Hughes ML, Field LL: Evidence for a susceptibility locus on chromosome 6q influencing phonological coding dyslexia. Am J Med Genet 2001;105:507–517.
  22. Cardon LR, Smith SD, Fulker DW, Kimberling WJ, Pennington BF, DeFries JC: Quantitative trait locus for reading disability: Erratum. Science 1995;268:1553.
  23. Londin ER, Meng H, Gruen JR: A transcription map of the 6p22.3 reading disability locus identifying candidate genes. BMC Genomics 2003;4:25.
  24. Ziegler A: Sampling strategies for model free linkage analyses of quantitative traits: implications for sib pair studies of reading and spelling disabilities to minimize the total study cost. Eur Child Adolesc Psychiatry 1999;8:35–39.
  25. Strehlow U, Kluge R, Möller H, Haffner J: Long-term course of dyslexia beyond the school years: catamnesis from pediatric psychiatric ambulatory care. Z Kinder Jugendpsychiatr 1992;20:254–265.
  26. Ziegler A: Genetische Kartierung quantitativer Phänotypen. Eine İbersicht über modellfreie kopplungsanalytische Verfahren. München, Urban & Vogel, Medien und Medizinverlag, 1999.
  27. Risch N, Zhang H: Extreme discordant sib pairs for mapping quantitative trait loci in humans. Science 1995;268:1584–1589.
  28. Neale MC, Neale BM, Sullivan PF: Nonpaternity in linkage studies of extremely discordant sib pairs. Am J Hum Genet 2002;70:526–529.
  29. Allison DB: The use of discordant sibling pairs for finding genetic loci linked to obesity: Practical considerations. Int J Obes Relat Metab Disord 1996;20:553–560.
  30. Allison DB, Heo M, Schork NJ, Wong SL, Elston RC: Extreme selection strategies in gene mapping studies of oligogenic quantitative traits do not always increase power. Hum Hered 1998;48:97–107.
  31. Marlow AJ, Fisher SE, Richardson AJ, Francks C, Talcott JB, Monaco AP, Stein JF, Cardon LR: Investigation of quantitative measures related to reading disability in a large sample of sib-pairs from the UK. Behav Genet 2001;31:219–230.
  32. Marlow AJ, Fisher SE, Richardson AJ, Francks C, Talcott JB, Monaco AP, Stein JF, Cardon LR: Investigation of quantitative measures related to reading disability in a large sample of sib-pairs from the UK. Behav Genet 2001;31:219–230.
  33. Allison DB, Faith MS, Nathan JS: Risch’s lambda values for human obesity. Int J Obes Relat Metab Disord 1996;20:990–999.
  34. Risch N: Linkage strategies for genetically complex traits. I. Multilocus models. Am J Hum Genet 1990;46:222–228.
  35. Guo X, Elston RC: Two-stage global search designs for linkage analysis I: Use of the mean statistic for affected sib pairs. Genet Epidemiol 2000;18:97–110.
  36. Böddeker IR, Müller H-H, Kress R, Geller F, Ziegler A, Schäfer H: The use of sequential designs in genome scans for asthma susceptibility loci with affected sib pairs. Genet Epidemiol 2001;21:S49–54.
  37. König IR, Schäfer H, Müller H-H, Ziegler A: Optimized group sequential study designs for tests of genetic linkage and association in complex diseases. Am J Hum Genet 2001;69:590–600.
  38. Kruglyak L, Lander ES: High-resolution genetic mapping of complex traits. Am J Hum Genet 1995;56:1212–1223.
  39. Kruglyak L, Lander ES: Limits on fine mapping of complex traits. Am J Hum Genet 1996;58:1092–1093.
  40. Gu C, Rao DC: A linkage strategy for detection of human quantitative-trait loci. I. Generalized relative risk ratios and power of sib pairs with extreme trait values. Am J Hum Genet 1997;61:200–210.
  41. Ziegler A, Schäfer H, Hebebrand J: Risch’s lambda values for human obesity estimated from segregation analysis. Int J Obes Relat Metab Disord 1997;21:952–953.
  42. Willcutt EG, Pennington BF, Smith SD, Cardon LR, Gayan J, Knopik VS, Olson RK, DeFries JC: Quantitative trait locus for reading disability on chromosome 6p is pleiotropic for attention-deficit/hyperactivity disorder. Am J Med Genet 2002;114:260–268.
  43. Brähler E, Holling V, Leutner D, Petermann F: Brickenkamp Handbuch psychologischer und pädagogischer Tests. Göttingen, Hogrefe, 2002.
  44. Olson JM, Cordell HJ: Ascertainment bias in the estimation of sibling genetic risk parameters. Genet Epidemiol 2000;18:217–235.
  45. Weiβ RH, Osterland J: Grundintelligenztest Skala 1 CFT 1. Göttingen, Hogrefe, 1997.
  46. Weiβ RH: Grundintelligenztest Skala 2 CFT 20. Göttingen, Hogrefe, 1998.
  47. Landerl K, Wimmer H, Moser E: SLRT – Salzburger Lese- und Rechtschreibtest. Bern, Hans Huber, 1997.
  48. Schulte-Körne G, Bartling J, Deimel W, Remschmidt H: Visual evoked potentials elicited by coherently moving dots in dyslexic children. Neurosci Lett 2004;357:207–210.
  49. Royston P, Altman DG: Regression using fractional polynomials of continuous covariats: Parsimonious parametric modelling. Appl Stat 1994;43:429–467.

    External Resources

  50. Sheskin DJ: Handbook of parametric and nonparametric statistical procedures. Boca Raton, Chapman & Hall/CRC, 2000.

  

Author Contacts

Prof. Dr. Andreas Ziegler
Institut für Medizinische Biometrie und Statistik
Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Universität zu Lübeck
Ratzeburger Allee 160, Haus 4, DE–23538 Lübeck (Germany)
Tel. +49 451 500 2780, Fax +49 451 500 2999, E-Mail ziegler@imbs.uni-luebeck.de

  

Article Information

Received: September 7, 2004
Accepted after revision: February 1, 2005
Published online: May 2, 2005
Number of Print Pages : 8
Number of Figures : 0, Number of Tables : 2, Number of References : 50

  

Publication Details

Human Heredity (International Journal of Human and Medical Genetics)

Vol. 59, No. 3, Year 2005 (Cover Date: Released June 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: Several studies have demonstrated a genetic component for dyslexia. However, both segregation and linkage analyses show contradictory results pointing at the necessity of an optimal ascertainment scheme for molecular genetic studies. Previously, we have argued that the single proband sib pair design (SPSP) would be optimal. The aims of this paper therefore are to demonstrate the practicability of the SPSP design and the estimation of recurrence risks for reading and writing. Methods: We assessed spelling and reading in a family sample ascertained through the SPSP design. 287 families with at least two siblings and their parents were recruited. At least one child was affected with spelling disorder according to a one standard deviation (1SD) discrepancy criterion. Results: Mean values for probands and their siblings were different for both the spelling and the reading phenotype. For the probands, variances of the phenotype spelling were smaller. These effects became stronger with more extreme selection criteria. Both siblings fulfilled the 1SD criterion for spelling and reading in 60.3 and 28.9% of the families, respectively, indicating a low cost efficiency of the double proband sib pair approach. A recurrence risk of 4.52 (CI: 4.07–4.93) was obtained for spelling when the 1SD criterion was applied to both siblings. Recurrence risk estimates were similar for reading. Conclusion: The study demonstrates the suitability of the SPSP design for genetic analysis of dyslexia. The recurrence risk estimates may be used for determining sample sizes in gene mapping studies.

© 2005 S. Karger AG, Basel


  

Author Contacts

Prof. Dr. Andreas Ziegler
Institut für Medizinische Biometrie und Statistik
Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Universität zu Lübeck
Ratzeburger Allee 160, Haus 4, DE–23538 Lübeck (Germany)
Tel. +49 451 500 2780, Fax +49 451 500 2999, E-Mail ziegler@imbs.uni-luebeck.de

  

Article Information

Received: September 7, 2004
Accepted after revision: February 1, 2005
Published online: May 2, 2005
Number of Print Pages : 8
Number of Figures : 0, Number of Tables : 2, Number of References : 50

  

Publication Details

Human Heredity (International Journal of Human and Medical Genetics)

Vol. 59, No. 3, Year 2005 (Cover Date: Released June 2005)

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

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


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 9/7/2004
Accepted: 2/1/2005
Published online: 6/17/2005
Issue release date: June 2005

Number of Print Pages: 8
Number of Figures: 0
Number of Tables: 2

ISSN: 0001-5652 (Print)
eISSN: 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. Francks C, MacPhie IL, Monaco AP: The genetic basis of dyslexia. Lancet Neurol 2002;1:483–490.
  2. Schulte-Körne G: Annotation: Genetics of reading and spelling disorder. J Child Psychol Psychiatry 2001;42:985–997.
  3. Francks C, Fisher SE, Olson RK, Pennington BF, Smith SD, DeFries JC, Monaco AP: Fine mapping of the chromosome 2p12–16 dyslexia susceptibility locus: quantitative association analysis and positional candidate genes SEMA4F and OTX1. Psychiatr Genet 2002;12:35–41.
  4. Schulte-Körne G: Legasthenie und Sprachwahrnehmung. Münster, Waxmann, 2001.
  5. Lewitter FI, DeFries JC, Elston RC: Genetic models of reading disability. Behav Genet 1980;10:9–30.
  6. Pennington BF, Gilger JW, Pauls D, Smith SA, Smith SD, DeFries JC: Evidence for major gene transmission of developmental dyslexia. J Am Med Assoc 1991;266:1527–1534.
  7. Chapman NH, Raskind WH, Thomson JB, Berninger VW, Wijsman EM: Segregation analysis of phenotypic components of learning disabilities. II. Phonological decoding. Am J Med Genet 2003;121B:60–70.
  8. Wijsman EM, Peterson D, Leutenegger AL, Thomson JB, Goddard KA, Hsu L, Berninger VW, Raskind WH: Segregation analysis of phenotypic components of learning disabilities. I. Nonword memory and digit span. Am J Hum Genet 2000;67:631–646.
  9. Gilger JW, Borecki IB, DeFries JC, Pennington BF: Commingling and segregation analysis of reading performance in families of normal reading probands. Behav Genet 1994;24:345–355.
  10. Lewis BA, Cox NJ, Byard PJ: Segregation analysis of speech and language disorders. Behav Genet 1993;23:291–297.
  11. Ziegler A, Hebebrand J: Sample size calculations for linkage analysis using extreme sib pairs based on segregation analysis with the quantitative phenotype body weight as an example. Genet Epidemiol 1998;15:577–593.
  12. Grigorenko EL, Wood FB, Meyer MS, Pauls JE, Hart LA, Pauls DL: Linkage studies suggest a possible locus for developmental dyslexia on chromosome 1p. Am J Med Genet 2001;105:120–129.
  13. Rabin M, Wen XL, Hepburn M, Lubs HA, Feldman E, Duara R: Suggestive linkage of developmental dyslexia to chromosome 1p34-p36. Lancet 1993;342:178.
  14. Kaminen N, Hannula-Jouppi K, Kestila M, Lahermo P, Muller K, Kaaranen M, Myllyluoma B, Voutilainen A, Lyytinen H, Nopola-Hemmi J, Kere J: A genome scan for developmental dyslexia confirms linkage to chromosome 2p11 and suggests a new locus on 7q32. J Med Genet 2003;40:340–345.
  15. Grigorenko EL, Wood FB, Meyer MS, Hart LA, Speed WC, Shuster A, Pauls DL: Susceptibility loci for distinct components of developmental dyslexia on chromosomes 6 and 15. Am J Hum Genet 1997;60:27–39.
  16. Kaplan DE, Gayan J, Ahn J, Won TW, Pauls D, Olson RK, DeFries JC, Wood F, Pennington BF, Page GP, Smith SD, Gruen JR: Evidence for linkage and association with reading disability on 6p21.3–22. Am J Hum Genet 2002;70:1287–1298.
  17. Schulte-Körne G, Grimm T, Nöthen MM, Müller-Myhsok B, Cichon S, Vogt IR, Propping P, Remschmidt H: Evidence for linkage of spelling disability to chromosome 15. Am J Hum Genet 1998;63:279–282.
  18. Fisher SE, Francks C, Marlow AJ, MacPhie IL, Newbury DF, Cardon LR, Ishikawa-Brush Y, Richardson AJ, Talcott JB, Gayán J, Olson RK, Pennington BF, Smith SD, DeFries JC, Stein JF, Monaco AP: Independent genome-wide scans identify a chromosome 18 quantitative-trait locus influencing dyslexia. Nat Genet 2001;17:17.
  19. Cardon LR, Smith SD, Fulker DW, Kimberling WJ, Pennington BF, DeFries JC: Quantitative trait locus for reading disability on chromosome 6. Science 1994;266:276–279.
  20. Field LL, Kaplan BJ: Absence of linkage of phonological coding dyslexia to chromosome 6p23-p21.3 in a large family data set. Am J Hum Genet 1998;63:1448–1456.
  21. Petryshen TL, Kaplan BJ, Fu Liu M, de French NS, Tobias R, Hughes ML, Field LL: Evidence for a susceptibility locus on chromosome 6q influencing phonological coding dyslexia. Am J Med Genet 2001;105:507–517.
  22. Cardon LR, Smith SD, Fulker DW, Kimberling WJ, Pennington BF, DeFries JC: Quantitative trait locus for reading disability: Erratum. Science 1995;268:1553.
  23. Londin ER, Meng H, Gruen JR: A transcription map of the 6p22.3 reading disability locus identifying candidate genes. BMC Genomics 2003;4:25.
  24. Ziegler A: Sampling strategies for model free linkage analyses of quantitative traits: implications for sib pair studies of reading and spelling disabilities to minimize the total study cost. Eur Child Adolesc Psychiatry 1999;8:35–39.
  25. Strehlow U, Kluge R, Möller H, Haffner J: Long-term course of dyslexia beyond the school years: catamnesis from pediatric psychiatric ambulatory care. Z Kinder Jugendpsychiatr 1992;20:254–265.
  26. Ziegler A: Genetische Kartierung quantitativer Phänotypen. Eine İbersicht über modellfreie kopplungsanalytische Verfahren. München, Urban & Vogel, Medien und Medizinverlag, 1999.
  27. Risch N, Zhang H: Extreme discordant sib pairs for mapping quantitative trait loci in humans. Science 1995;268:1584–1589.
  28. Neale MC, Neale BM, Sullivan PF: Nonpaternity in linkage studies of extremely discordant sib pairs. Am J Hum Genet 2002;70:526–529.
  29. Allison DB: The use of discordant sibling pairs for finding genetic loci linked to obesity: Practical considerations. Int J Obes Relat Metab Disord 1996;20:553–560.
  30. Allison DB, Heo M, Schork NJ, Wong SL, Elston RC: Extreme selection strategies in gene mapping studies of oligogenic quantitative traits do not always increase power. Hum Hered 1998;48:97–107.
  31. Marlow AJ, Fisher SE, Richardson AJ, Francks C, Talcott JB, Monaco AP, Stein JF, Cardon LR: Investigation of quantitative measures related to reading disability in a large sample of sib-pairs from the UK. Behav Genet 2001;31:219–230.
  32. Marlow AJ, Fisher SE, Richardson AJ, Francks C, Talcott JB, Monaco AP, Stein JF, Cardon LR: Investigation of quantitative measures related to reading disability in a large sample of sib-pairs from the UK. Behav Genet 2001;31:219–230.
  33. Allison DB, Faith MS, Nathan JS: Risch’s lambda values for human obesity. Int J Obes Relat Metab Disord 1996;20:990–999.
  34. Risch N: Linkage strategies for genetically complex traits. I. Multilocus models. Am J Hum Genet 1990;46:222–228.
  35. Guo X, Elston RC: Two-stage global search designs for linkage analysis I: Use of the mean statistic for affected sib pairs. Genet Epidemiol 2000;18:97–110.
  36. Böddeker IR, Müller H-H, Kress R, Geller F, Ziegler A, Schäfer H: The use of sequential designs in genome scans for asthma susceptibility loci with affected sib pairs. Genet Epidemiol 2001;21:S49–54.
  37. König IR, Schäfer H, Müller H-H, Ziegler A: Optimized group sequential study designs for tests of genetic linkage and association in complex diseases. Am J Hum Genet 2001;69:590–600.
  38. Kruglyak L, Lander ES: High-resolution genetic mapping of complex traits. Am J Hum Genet 1995;56:1212–1223.
  39. Kruglyak L, Lander ES: Limits on fine mapping of complex traits. Am J Hum Genet 1996;58:1092–1093.
  40. Gu C, Rao DC: A linkage strategy for detection of human quantitative-trait loci. I. Generalized relative risk ratios and power of sib pairs with extreme trait values. Am J Hum Genet 1997;61:200–210.
  41. Ziegler A, Schäfer H, Hebebrand J: Risch’s lambda values for human obesity estimated from segregation analysis. Int J Obes Relat Metab Disord 1997;21:952–953.
  42. Willcutt EG, Pennington BF, Smith SD, Cardon LR, Gayan J, Knopik VS, Olson RK, DeFries JC: Quantitative trait locus for reading disability on chromosome 6p is pleiotropic for attention-deficit/hyperactivity disorder. Am J Med Genet 2002;114:260–268.
  43. Brähler E, Holling V, Leutner D, Petermann F: Brickenkamp Handbuch psychologischer und pädagogischer Tests. Göttingen, Hogrefe, 2002.
  44. Olson JM, Cordell HJ: Ascertainment bias in the estimation of sibling genetic risk parameters. Genet Epidemiol 2000;18:217–235.
  45. Weiβ RH, Osterland J: Grundintelligenztest Skala 1 CFT 1. Göttingen, Hogrefe, 1997.
  46. Weiβ RH: Grundintelligenztest Skala 2 CFT 20. Göttingen, Hogrefe, 1998.
  47. Landerl K, Wimmer H, Moser E: SLRT – Salzburger Lese- und Rechtschreibtest. Bern, Hans Huber, 1997.
  48. Schulte-Körne G, Bartling J, Deimel W, Remschmidt H: Visual evoked potentials elicited by coherently moving dots in dyslexic children. Neurosci Lett 2004;357:207–210.
  49. Royston P, Altman DG: Regression using fractional polynomials of continuous covariats: Parsimonious parametric modelling. Appl Stat 1994;43:429–467.

    External Resources

  50. Sheskin DJ: Handbook of parametric and nonparametric statistical procedures. Boca Raton, Chapman & Hall/CRC, 2000.