An application of conditional logistic regression and multifactor dimensionality reduction for detecting gene-gene Interactions on risk of myocardial infarction: The importance of model validation

Christopher S Coffey; Patricia R Hebert; Marylyn D Ritchie; Harlan M Krumholz; J Michael Gaziano; Paul M Ridker; Nancy J Brown; Douglas E Vaughan; Jason H Moore

doi:10.1186/1471-2105-5-49

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An application of conditional logistic regression and multifactor dimensionality reduction for detecting gene-gene Interactions on risk of myocardial infarction: The importance of model validation

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An application of conditional logistic regression and multifactor dimensionality reduction for detecting gene-gene Interactions on risk of myocardial infarction: The importance of model validation

Christopher S Coffey, Patricia R Hebert, Marylyn D Ritchie, Harlan M Krumholz, J Michael Gaziano, Paul M Ridker, Nancy J Brown, Douglas E Vaughan and Jason H Moore

BMC bioinformatics, Vol.5(1), pp.49-49

04/30/2004

DOI: 10.1186/1471-2105-5-49

PMCID: PMC419697

PMID: 15119966

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Abstract

Background: To examine interactions among the angiotensin converting enzyme (ACE) insertion/deletion, plasminogen activator inhibitor-1 (PAI-1) 4G/5G, and tissue plasminogen activator (t-PA) insertion/deletion gene polymorphisms on risk of myocardial infarction using data from 343 matched case-control pairs from the Physicians Health Study. We examined the data using both conditional logistic regression and the multifactor dimensionality reduction (MDR) method. One advantage of the MDR method is that it provides an internal prediction error for validation. We summarize our use of this internal prediction error for model validation. Results: The overall results for the two methods were consistent, with both suggesting an interaction between the ACE I/D and PAI-1 4G/5G polymorphisms. However, using ten-fold cross validation, the 46% prediction error for the final MDR model was not significantly lower than that expected by chance. Conclusions: The significant interaction initially observed does not validate and may represent a type I error. As data-driven analytic methods continue to be developed and used to examine complex genetic interactions, it will become increasingly important to stress model validation in order to ensure that significant effects represent true relationships rather than chance findings. © 2004 Coffey et al, licensee BioMed Central Ltd.

cross validation

epistasis

prediction error

Details

Title: Subtitle: An application of conditional logistic regression and multifactor dimensionality reduction for detecting gene-gene Interactions on risk of myocardial infarction: The importance of model validation
Creators: Christopher S Coffey - Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL 35294-0022, USA Section of Cardiovascular Medicine, Department of Medicine, Yale University School of Medicine, New Haven, CT 06510, USA Center for Human Genetics Research, Department of Molecular Physiology and Biophysics, Vanderbilt University Medical School, Nashville, TN 37232-0700, USA Section of Health Policy and Administration, Department of Epidemiology and Public Health and Robert Wood Johnson Clinical Scholars Program, Yale University School of Medicine, New Haven, CT 06510, USA Yale-New Haven Hospital Center for Outcomes Research and Evaluation, New Haven, CT 06510, USA Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA Departments of Medicine and Pharmacology, Vanderbilt University Medical School, Nashville, TN 37232-0700, USA
Patricia R Hebert - Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL 35294-0022, USA Section of Cardiovascular Medicine, Department of Medicine, Yale University School of Medicine, New Haven, CT 06510, USA Center for Human Genetics Research, Department of Molecular Physiology and Biophysics, Vanderbilt University Medical School, Nashville, TN 37232-0700, USA Section of Health Policy and Administration, Department of Epidemiology and Public Health and Robert Wood Johnson Clinical Scholars Program, Yale University School of Medicine, New Haven, CT 06510, USA Yale-New Haven Hospital Center for Outcomes Research and Evaluation, New Haven, CT 06510, USA Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA Departments of Medicine and Pharmacology, Vanderbilt University Medical School, Nashville, TN 37232-0700, USA
Marylyn D Ritchie - Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL 35294-0022, USA Section of Cardiovascular Medicine, Department of Medicine, Yale University School of Medicine, New Haven, CT 06510, USA Center for Human Genetics Research, Department of Molecular Physiology and Biophysics, Vanderbilt University Medical School, Nashville, TN 37232-0700, USA Section of Health Policy and Administration, Department of Epidemiology and Public Health and Robert Wood Johnson Clinical Scholars Program, Yale University School of Medicine, New Haven, CT 06510, USA Yale-New Haven Hospital Center for Outcomes Research and Evaluation, New Haven, CT 06510, USA Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA Departments of Medicine and Pharmacology, Vanderbilt University Medical School, Nashville, TN 37232-0700, USA
Harlan M Krumholz - Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL 35294-0022, USA Section of Cardiovascular Medicine, Department of Medicine, Yale University School of Medicine, New Haven, CT 06510, USA Center for Human Genetics Research, Department of Molecular Physiology and Biophysics, Vanderbilt University Medical School, Nashville, TN 37232-0700, USA Section of Health Policy and Administration, Department of Epidemiology and Public Health and Robert Wood Johnson Clinical Scholars Program, Yale University School of Medicine, New Haven, CT 06510, USA Yale-New Haven Hospital Center for Outcomes Research and Evaluation, New Haven, CT 06510, USA Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA Departments of Medicine and Pharmacology, Vanderbilt University Medical School, Nashville, TN 37232-0700, USA
J Michael Gaziano - Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL 35294-0022, USA Section of Cardiovascular Medicine, Department of Medicine, Yale University School of Medicine, New Haven, CT 06510, USA Center for Human Genetics Research, Department of Molecular Physiology and Biophysics, Vanderbilt University Medical School, Nashville, TN 37232-0700, USA Section of Health Policy and Administration, Department of Epidemiology and Public Health and Robert Wood Johnson Clinical Scholars Program, Yale University School of Medicine, New Haven, CT 06510, USA Yale-New Haven Hospital Center for Outcomes Research and Evaluation, New Haven, CT 06510, USA Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA Departments of Medicine and Pharmacology, Vanderbilt University Medical School, Nashville, TN 37232-0700, USA
Paul M Ridker - Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL 35294-0022, USA Section of Cardiovascular Medicine, Department of Medicine, Yale University School of Medicine, New Haven, CT 06510, USA Center for Human Genetics Research, Department of Molecular Physiology and Biophysics, Vanderbilt University Medical School, Nashville, TN 37232-0700, USA Section of Health Policy and Administration, Department of Epidemiology and Public Health and Robert Wood Johnson Clinical Scholars Program, Yale University School of Medicine, New Haven, CT 06510, USA Yale-New Haven Hospital Center for Outcomes Research and Evaluation, New Haven, CT 06510, USA Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA Departments of Medicine and Pharmacology, Vanderbilt University Medical School, Nashville, TN 37232-0700, USA
Nancy J Brown - Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL 35294-0022, USA Section of Cardiovascular Medicine, Department of Medicine, Yale University School of Medicine, New Haven, CT 06510, USA Center for Human Genetics Research, Department of Molecular Physiology and Biophysics, Vanderbilt University Medical School, Nashville, TN 37232-0700, USA Section of Health Policy and Administration, Department of Epidemiology and Public Health and Robert Wood Johnson Clinical Scholars Program, Yale University School of Medicine, New Haven, CT 06510, USA Yale-New Haven Hospital Center for Outcomes Research and Evaluation, New Haven, CT 06510, USA Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA Departments of Medicine and Pharmacology, Vanderbilt University Medical School, Nashville, TN 37232-0700, USA
Douglas E Vaughan - Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL 35294-0022, USA Section of Cardiovascular Medicine, Department of Medicine, Yale University School of Medicine, New Haven, CT 06510, USA Center for Human Genetics Research, Department of Molecular Physiology and Biophysics, Vanderbilt University Medical School, Nashville, TN 37232-0700, USA Section of Health Policy and Administration, Department of Epidemiology and Public Health and Robert Wood Johnson Clinical Scholars Program, Yale University School of Medicine, New Haven, CT 06510, USA Yale-New Haven Hospital Center for Outcomes Research and Evaluation, New Haven, CT 06510, USA Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA Departments of Medicine and Pharmacology, Vanderbilt University Medical School, Nashville, TN 37232-0700, USA
Jason H Moore - Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL 35294-0022, USA Section of Cardiovascular Medicine, Department of Medicine, Yale University School of Medicine, New Haven, CT 06510, USA Center for Human Genetics Research, Department of Molecular Physiology and Biophysics, Vanderbilt University Medical School, Nashville, TN 37232-0700, USA Section of Health Policy and Administration, Department of Epidemiology and Public Health and Robert Wood Johnson Clinical Scholars Program, Yale University School of Medicine, New Haven, CT 06510, USA Yale-New Haven Hospital Center for Outcomes Research and Evaluation, New Haven, CT 06510, USA Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA Departments of Medicine and Pharmacology, Vanderbilt University Medical School, Nashville, TN 37232-0700, USA
Resource Type: Journal article
Publication Details: BMC bioinformatics, Vol.5(1), pp.49-49
Publisher: BioMed Central
DOI: 10.1186/1471-2105-5-49
PMID: 15119966
PMCID: PMC419697
ISSN: 1471-2105
eISSN: 1471-2105
Language: English
Date published: 04/30/2004
Academic Unit: Biostatistics
Record Identifier: 9984214822902771

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