Login to MyKarger

New to MyKarger? Click here to sign up.

Login with Facebook

Forgot Password? Reset your password

Authors, Editors, Reviewers

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

Submission Websites List

Institutional Login (Shibboleth)

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

Table of Contents
Vol. 72, No. 3, 2011
Issue release date: November 2011
Section title: Original Paper
Free Access
Hum Hered 2011;72:161–172

Detection of Intergenerational Genetic Effects with Application to HLA-B Matching as a Risk Factor for Schizophrenia

Childs E.J.a · Sobel E.M.b · Palmer C.G.S.b, c · Sinsheimer J.S.a, b, d
Departments of aBiostatistics, bHuman Genetics, cPsychiatry and Biobehavioral Sciences, and dBiomathematics, University of California, Los Angeles, Calif., USA
email Corresponding Author

Christina Palmer, PhD

UCLA Semel Institute

760 Westwood Plaza, Room 47-422, Los Angeles, CA 90095 (USA)

Tel. +1 310 794 4796, E-Mail cpalmer@mednet.ucla.edu

Janet Sinsheimer, PhD

UCLA Gonda Center

695 Charles E. Young Drive South, 5357-C

Los Angeles, CA 90095 (USA)

Tel. +1 310 825 8002, E-Mail janet@mednet.ucla.edu

Do you have an account?

Login Information

Contact Information

I have read the Karger Terms and Conditions and agree.


Background and Methods: Association studies using unrelated individuals cannot detect intergenerational genetic effects contributing to disease. To detect these effects, we improve the extended maternal-fetal genotype (EMFG) incompatibility test to estimate any combination of maternal effects, offspring effects, and their interactions at polymorphic loci or multiple SNPs, using any size pedigrees. We explore the advantages of using extended pedigrees rather than nuclear families. We apply our methods to schizophrenia pedigrees to investigate whether the previously associated mother-daughter HLA-B matching is a genuine risk or the result of bias. Results: Simulations demonstrate that using the EMFG test with extended pedigrees increases power and precision, while partitioning extended pedigrees into nuclear families can underestimate intergenerational effects. Application to actual data demonstrates that mother-daughter HLA-B matching remains a schizophrenia risk factor. Furthermore, ascertainment and mate selection biases cannot by themselves explain the observed HLA-B matching and schizophrenia association. Conclusions: Our results demonstrate the power of the EMFG test to examine intergenerational genetic effects, highlight the importance of pedigree rather than case/control or case-mother/control-mother designs, illustrate that pedigrees provide a means to examine alternative, non-causal mechanisms, and they strongly support the hypothesis that HLA-B matching is causally involved in the etiology of schizophrenia in females.

© 2011 S. Karger AG, Basel

Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: June 02, 2011
Accepted: August 23, 2011
Published online: October 15, 2011
Issue release date: November 2011

Number of Print Pages: 12
Number of Figures: 1
Number of Tables: 5

ISSN: 0001-5652 (Print)
eISSN: 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 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.