Login to MyKarger

New to MyKarger? Click here to sign up.



Login with Facebook

Forgot your password?

Authors, Editors, Reviewers

For Manuscript Submission, Check or Review Login please go to Submission Websites List.

Submission Websites List

Institutional Login
(Shibboleth or Open Athens)

For the academic login, please select your country in the dropdown list. You will be redirected to verify your credentials.

Original Paper

A Genome-Wide Scan for Loci Affecting Normal Adult Height in the Framingham Heart Study

Mukhopadhyay N.a · Finegold D.N.a · Larson M.G.b · Cupples L.A.c · Myers R.H.d · Weeks D.E.a,e

Author affiliations

aDepartment of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pa.; bFramingham Heart Study, Framingham, Mass; cDepartment of Biostatistics, School of Public Health, Boston University, Boston, Mass; dDepartment of Neurology, Boston University School of Medicine, Boston, Mass; eDepartment of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pa., USA

Related Articles for ""

Hum Hered 2003;55:191–201

Do you have an account?

Login Information





Contact Information











I have read the Karger Terms and Conditions and agree.



Login Information





Contact Information











I have read the Karger Terms and Conditions and agree.



To view the fulltext, please log in

To view the pdf, please log in

Buy

  • FullText & PDF
  • Unlimited re-access via MyKarger
  • Unrestricted printing, no saving restrictions for personal use
read more

CHF 38.00 *
EUR 35.00 *
USD 39.00 *

Select

KAB

Buy a Karger Article Bundle (KAB) and profit from a discount!

If you would like to redeem your KAB credit, please log in.


Save over 20% compared to the individual article price.
Learn more

Rent/Cloud

  • Rent for 48h to view
  • Buy Cloud Access for unlimited viewing via different devices
  • Synchronizing in the ReadCube Cloud
  • Printing and saving restrictions apply

Rental: USD 8.50
Cloud: USD 20.00


Select

Subscribe

  • Access to all articles of the subscribed year(s) guaranteed for 5 years
  • Unlimited re-access via Subscriber Login or MyKarger
  • Unrestricted printing, no saving restrictions for personal use
read more

Subcription rates


Select

* The final prices may differ from the prices shown due to specifics of VAT rules.

Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: November 04, 2002
Accepted: May 28, 2003
Published online: October 22, 2003
Issue release date: October 2003

Number of Print Pages: 11
Number of Figures: 1
Number of Tables: 3

ISSN: 0001-5652 (Print)
eISSN: 1423-0062 (Online)

For additional information: https://www.karger.com/HHE

Abstract

Objective: To map loci influencing normal adult height in 335 families from the Framingham Heart Study. Methods: We analyzed data consisting of 1,702 genotyped individuals who have been followed over time. The first height measurement for individuals between the ages 20–55 years was analyzed in a genome-wide scan using variance component linkage analysis. Sex, age, and cohort effects were removed before analysis. Results: Two regions (18pter-p11, 22q11.2) with multipoint LOD scores >1.0 (–log p values >2.0) were detected: we obtained LOD scores of 1.38 at D18S1364, and of 1.10 at D22S345. Analysis of height as a sex-limited phenotype revealed a peak in the 9p21 region near D9S319 with a maximum LOD score of 1.65 (–log p value >3.0) when only male height phenotypes were used. When only female phenotypes were used, a peak with a maximum LOD score of 1.85 (–log p value of 2.70) was observed in the 11q25-qter region near D11S2359. Conclusions: Our region of interest on chromosome 9 has been implicated by two prior studies. Variance components analysis appeared to be sensitive to pedigree structures as well as the method of IBD computation used.

© 2003 S. Karger AG, Basel


References

  1. Pearson K, Lee A: On the laws of inheritance in man. I. Inheritance of physical characters. Biometrika 1903;2:357–462.
  2. Roberts DF, Billewicz WZ, McGregor IA: Heritability of stature in a West African population. Ann Hum Genet 1978;42:15–24.
  3. Solomon PJ, Thompson EA, Rissanen A: The inheritance of height in a Finnish population. Ann Hum Biol 1983;10:247–256.
  4. Furusho T: On the manifestation of genotypes responsible for stature. Hum Biol 1968;40:437–455.
  5. Kaur DP, Singh R: Parent-adult offspring correlations and heritability of body measurements in a rural Indian population. Ann Hum Biol 1981;8:333–339.
  6. Tanksley SD: Mapping polygenes. Annu Rev Genet 1993;27:205–253.
  7. Mackay TF: The genetic architecture of quantitative traits. Annu Rev Genet 2001;35:303–339.
  8. Bost B, de Vienne D, Hospital F, Moreau L, Dillmann C: Genetic and nongenetic bases for the L-shaped distribution of quantitative trait loci effects. Genetics 2001;157:1773–1787.
  9. Ginsburg E, Livshits G, Yakovenko K, Kobyliansky E: Major gene control of human body height, weight and BMI in five ethnically different populations. Ann Hum Genet 1998;62:307–322.
    External Resources
  10. Minamitani K, Takahashi Y, Minagawa M, Yasuda T, Niimi H: Difference in height associated with a translation start site polymorphism in the vitamin D receptor gene. Pediatr Res 1998;44:628–632.
  11. Arinami T, Iijima Y, Yamakawa-Kobayashi K, Ishiguro H, Ohtsuki T, Yanagi H, Shimakura Y, Ishikawa H, Hamaguchi H: Supportive evidence for contribution of the dopamine D2 receptor gene to heritability of stature: Linkage and association studies. Ann Hum Genet 1999;63:147–151.
    External Resources
  12. Binder G, Schwarze CP, Ranke MB: Identification of short stature caused by SHOX defects and therapeutic effect of recombinant human growth hormone. J Clin Endocrinol Metab 2000;85:245–249.
  13. Hasegawa Y, Fujii K, Yamada M, Igarashi Y, Tachibana K, Tanaka T, Onigata K, Nishi Y, Kato S, Hasegawa T: Identification of novel human GH-1 gene polymorphisms that are associated with growth hormone secretion and height. J Clin Endocrinol Metab 2000;85:1290–1295.
  14. Thompson DB, Ossowski V, Janssen RC, Knowler WC, Bogardus C: Linkage between stature and a region on chromosome 20 and analysis of a candidate gene, bone morphogenetic protein 2. Am J Med Genet 1995;59:495–500.
  15. Hirschhorn JN, Lindgren CM, Daly MJ, Kirby A, Schaffner SF, Burtt NP, Altshuler D, Parker A, Rioux JD, Platko J, Gaudet D, Hudson TJ, Groop LC, Lander ES: Genomewide linkage analysis of stature in multiple populations reveals several regions with evidence of linkage to adult height. Am J Hum Genet 2001;69:106–116.
  16. Perola M, Ohman M, Hiekkalinna T, Leppavuori J, Pajukanta P, Wessman M, Koskenvuo M, Palotie A, Lange K, Kaprio J, Peltonen L: Quantitative-trait-locus analysis of body-mass index and of stature, by combined analysis of genome scans of five Finnish study groups. Am J Hum Genet 2001;69:117–123.
  17. Wiltshire S, Frayling TM, Hattersley AT, Hitman GA, Walker M, Levy JC, O’Rahilly S, Groves CJ, Menzel S, Cardon LR, McCarthy MI: Evidence for linkage of stature to chromosome 3p26 in a large U.K. family data set ascertained for type 2 diabetes. Am J Hum Genet 2002;70:543–546.
  18. Xu J, Bleecker ER, Jongepier H, Howard TD, Koppelman GH, Postma DS, Meyers DA: Major recessive gene(s) with considerable residual polygenic effect regulating adult height: Confirmation of genomewide scan results for chromosomes 6, 9, and 12. Am J Hum Genet 2002;71:646–650.
  19. Deng HW, Xu FH, Liu YZ, Shen H, Deng H, Huang QY, Liu YJ, Conway T, Li JL, Davies KM, Recker RR: A whole-genome linkage scan suggests several genomic regions potentially containing QTLs underlying the variation of stature. Am J Med Genet 2002;113:29–39.
  20. Wu X, Cooper RS, Boerwinkle E, Turner ST, Hunt S, Myers R, Olshen RA, Curb D, Zhu X, Kan D, Luke A: Combined analysis of genomewide scans for adult height: Results from the NHLBI Family Blood Pressure Program. Eur J Hum Genet 2003;11:271–274.
  21. Mukhopadhyay N, Finegold DN, Larson M, Cupples LA, Myers RH, Ferrell R, Weeks DE: Heritability of height and assortative mating in the Framingham Study. Am J Hum Genet 2000;67(suppl 2):235.
  22. Mukhopadhyay N, Finegold DN, Larson M, Cupples LA, Myers RH, Ferrell R, Weeks DE: Genome-wide scan for loci affecting normal adult height in the Framingham Study. Am J Hum Genet 2001;69(suppl):402.
  23. Kannel WB, Feinleib M, McNamara PM, Garrison RJ, Castelli WP: An investigation of coronary heart disease in families. The Framingham offspring study. Am J Epidemiol 1979;110:281–290.
  24. Dawber TR, Meadors GF, Moore FE Jr.: Epidemiological approaches to heart disease: The Framingham Study. Am J Public Health 1951;41:279–286.
  25. Almasy L, Blangero J: Multipoint quantitative-trait linkage analysis in general pedigrees. Am J Hum Genet 1998;62:1198–1211.
  26. Lange K, Weeks D, Boehnke M: Programs for pedigree analysis: MENDEL, FISHER, and dGENE. Genet Epidemiol 1988;5:471–472.
  27. Elston RC, Statistical Analysis for Genetics Epidemiology, Release 4.0 (http://darwin. cwru.edu/pub/sage.html). 2001, Computer program package from the Department of Epidemiology and Biostatistics, Rammelkamp Center for Education and Research, MetroHealth Campus, Case Western Reserve University, Cleveland.
  28. Hinds D, Risch N: The ASPEX package: Affected sib-pair mapping. ftp://lahmed.stanford.edu/pub/aspex. 1996;
  29. McPeek MS, Sun L: Statistical tests for detection of misspecified relationships by use of genome-screen data. Am J Hum Genet 2000;66:1076–1094.
  30. Abecasis GR, Cherny SS, Cookson WO, Cardon LR: Merlin – Rapid analysis of dense genetic maps using sparse gene flow trees. Nat Genet 2002;30:97–101.
  31. Nagylaki T: The correlation between relatives with assortative mating. Ann Hum Genet 1978;42:131–137.
  32. Sobel E, Sengul H, Weeks DE: Multipoint estimation of IBD probabilities at arbitrary positions among marker loci on general pedigrees. Hum Hered 2001;52:121–131.
  33. Sobel E, Lange K: Descent graphs in pedigree analysis: Applications to haplotyping, location scores, and marker-sharing statistics. Am J Hum Genet 1996;58:1323–1337.
  34. Heath SC: Markov chain Monte Carlo segregation and linkage analysis for oligogenic models. Am J Hum Genet 1997;61:748–760.
  35. Atwood LD, Heard-Costa NL, Cupples LA, Jaquish CE, Wilson PW, D’Agostino RB: Genomewide linkage analysis of body mass index across 28 years of the Framingham Heart Study. Am J Hum Genet 2002;71:1044–1050.
  36. Cordell HJ: Sample size requirements to control for stochastic variation in magnitude and location of allele-sharing linkage statistics in affected sibling pairs. Ann Hum Genet 2001;65:491–502.
  37. Hsueh WC, Goring HH, Blangero J, Mitchell BD: Replication of linkage to quantitative trait loci: Variation in location and magnitude of the lod score. Genet Epidemiol 2001;21:S473–478.
  38. Roberts SB, MacLean CJ, Neale MC, Eaves LJ, Kendler KS: Replication of linkage studies of complex traits: an examination of variation in location estimates. Am J Hum Genet 1999;65:876–884.

Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: November 04, 2002
Accepted: May 28, 2003
Published online: October 22, 2003
Issue release date: October 2003

Number of Print Pages: 11
Number of Figures: 1
Number of Tables: 3

ISSN: 0001-5652 (Print)
eISSN: 1423-0062 (Online)

For additional information: https://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.
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 government 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.