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Family-Based Association Studies

Family-Based Association Studies We review case-control designs for studying gene associations in which relatives of case patients are used as control subjects. These designs have the advantage that they avoid the problem of population stratification that can lead to spurious associations with noncausal genes. We focus on designs that use sibling, cousin, or pseudosibling controls, the latter formed as the set of genotypes not transmitted to the case from his or her parents. We describe a common conditional likelihood framework for use in analyzing data from any of these designs and review what is known about the validity of the various design and analysis combinations for estimating the genetic relative risk. We also present comparisons of efficiency for each of the family-based designs relative to the standard population-control design in which unrelated controls are selected from the source population of cases. Because of overmatching on genotype, the use of sibling controls leads to estimates of genetic relative risk that are approximately half as efficient as those obtained with the use of population controls, while relative efficiency for cousin controls is approximately 90%. However, we find that, for a rare gene, the sibling-control design can lead to improved efficiency for estimating a G × E interaction effect. We also review some restricted designs that can substantially improve efficiency, e.g., restriction of the sample to case-sibling pairs with an affected parent. We conclude that family-based case-control studies are an attractive alternative to population-based case-control designs using unrelated control subjects. Oxford University Press « Previous | Next Article » Table of Contents This Article J Natl Cancer Inst Monogr (1999) 1999 (26): 31-37. This article appears in: Innovative Study Designs and Analytic Approaches to the Genetic Epidemiology of Cancer » Abstract Free Full Text (HTML) Free Full Text (PDF) Free Classifications II. GENE CHARACTERIZATION PANEL Services Article metrics Alert me when cited Alert me if corrected Find similar articles Similar articles in Web of Science Similar articles in PubMed Add to my archive Download citation Request Permissions Citing Articles Load citing article information Citing articles via CrossRef Citing articles via Scopus Citing articles via Web of Science Citing articles via Google Scholar Google Scholar Articles by Gauderman, W. J. Articles by Thomas, D. C. Search for related content PubMed PubMed citation Articles by Gauderman, W. J. Articles by Witte, J. S. Articles by Thomas, D. C. Related Content Load related web page information Share Email this article CiteULike Delicious Facebook Google+ Mendeley Twitter What's this? Search this journal: Advanced » Current Issue May 2015 2015 (51) Alert me to new issues The Journal About this journal Rights & Permissions We are mobile – find out more Journals Career Network Editor-in-Chief Carmen J. Allegra View the JNCI editorial board For Authors Instructions to authors Author Self Archiving Policy Alerting Services Email table of contents CiteTrack XML RSS feed Corporate Services Advertising sales Reprints var taxonomies = ("MED00300"); Most Most Read Clinical Practice Guidelines on the Use of Integrative Therapies as Supportive Care in Patients Treated for Breast Cancer Descriptive Review of the Literature on Breast Cancer Outcomes: 1990 Through 2000 Prevalence of Depression in Patients With Cancer Biology of Oral Mucosa and Esophagus Chapter 6: Estrogen Metabolism by Conjugation » View all Most Read articles Most Cited Chapter 1: Human Papillomavirus and Cervical Cancer--Burden and Assessment of Causality Chapter 4: Estrogens as Endogenous Genotoxic Agents--DNA Adducts and Mutations Prevalence of Depression in Patients With Cancer Preoperative Chemotherapy in Patients With Operable Breast Cancer: Nine-Year Results From National Surgical Adjuvant Breast and Bowel Project B-18 Overview of the Randomized Trials of Radiotherapy in Ductal Carcinoma In Situ of the Breast » View all Most Cited articles Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. 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Family-Based Association Studies

Family-Based Association Studies

JNCI Monographs , Volume 1999 (26) – Dec 1, 1999

Abstract

We review case-control designs for studying gene associations in which relatives of case patients are used as control subjects. These designs have the advantage that they avoid the problem of population stratification that can lead to spurious associations with noncausal genes. We focus on designs that use sibling, cousin, or pseudosibling controls, the latter formed as the set of genotypes not transmitted to the case from his or her parents. We describe a common conditional likelihood framework for use in analyzing data from any of these designs and review what is known about the validity of the various design and analysis combinations for estimating the genetic relative risk. We also present comparisons of efficiency for each of the family-based designs relative to the standard population-control design in which unrelated controls are selected from the source population of cases. Because of overmatching on genotype, the use of sibling controls leads to estimates of genetic relative risk that are approximately half as efficient as those obtained with the use of population controls, while relative efficiency for cousin controls is approximately 90%. However, we find that, for a rare gene, the sibling-control design can lead to improved efficiency for estimating a G × E interaction effect. We also review some restricted designs that can substantially improve efficiency, e.g., restriction of the sample to case-sibling pairs with an affected parent. We conclude that family-based case-control studies are an attractive alternative to population-based case-control designs using unrelated control subjects. Oxford University Press « Previous | Next Article » Table of Contents This Article J Natl Cancer Inst Monogr (1999) 1999 (26): 31-37. This article appears in: Innovative Study Designs and Analytic Approaches to the Genetic Epidemiology of Cancer » Abstract Free Full Text (HTML) Free Full Text (PDF) Free Classifications II. GENE CHARACTERIZATION PANEL Services Article metrics Alert me when cited Alert me if corrected Find similar articles Similar articles in Web of Science Similar articles in PubMed Add to my archive Download citation Request Permissions Citing Articles Load citing article information Citing articles via CrossRef Citing articles via Scopus Citing articles via Web of Science Citing articles via Google Scholar Google Scholar Articles by Gauderman, W. J. Articles by Thomas, D. C. Search for related content PubMed PubMed citation Articles by Gauderman, W. J. Articles by Witte, J. S. Articles by Thomas, D. C. Related Content Load related web page information Share Email this article CiteULike Delicious Facebook Google+ Mendeley Twitter What's this? Search this journal: Advanced » Current Issue May 2015 2015 (51) Alert me to new issues The Journal About this journal Rights & Permissions We are mobile – find out more Journals Career Network Editor-in-Chief Carmen J. Allegra View the JNCI editorial board For Authors Instructions to authors Author Self Archiving Policy Alerting Services Email table of contents CiteTrack XML RSS feed Corporate Services Advertising sales Reprints var taxonomies = ("MED00300"); Most Most Read Clinical Practice Guidelines on the Use of Integrative Therapies as Supportive Care in Patients Treated for Breast Cancer Descriptive Review of the Literature on Breast Cancer Outcomes: 1990 Through 2000 Prevalence of Depression in Patients With Cancer Biology of Oral Mucosa and Esophagus Chapter 6: Estrogen Metabolism by Conjugation » View all Most Read articles Most Cited Chapter 1: Human Papillomavirus and Cervical Cancer--Burden and Assessment of Causality Chapter 4: Estrogens as Endogenous Genotoxic Agents--DNA Adducts and Mutations Prevalence of Depression in Patients With Cancer Preoperative Chemotherapy in Patients With Operable Breast Cancer: Nine-Year Results From National Surgical Adjuvant Breast and Bowel Project B-18 Overview of the Randomized Trials of Radiotherapy in Ductal Carcinoma In Situ of the Breast » View all Most Cited articles Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department. Online ISSN 1745-6614 - Print ISSN 1052-6773 Copyright © 2015 Oxford University Press Oxford Journals Oxford University Press Site Map Privacy Policy Cookie Policy Legal Notices Frequently Asked Questions Other Oxford University Press sites: Oxford University Press Oxford Journals China Oxford Journals Japan Academic & Professional books Children's & Schools Books Dictionaries & Reference Dictionary of National Biography Digital Reference English Language Teaching Higher Education Textbooks International Education Unit Law Medicine Music Online Products & Publishing Oxford Bibliographies Online Oxford Dictionaries Online Oxford English Dictionary Oxford Language Dictionaries Online Oxford Scholarship Online Reference Rights and Permissions Resources for Retailers & Wholesalers Resources for the Healthcare Industry Very Short Introductions World's Classics function fnc_onDomLoaded() { var query_context = getQueryContext(); PF_initOIUnderbar(query_context,":QS:default","","JRN"); PF_insertOIUnderbar(0); }; if (window.addEventListener) { window.addEventListener('load', fnc_onDomLoaded, false); } else if (window.attachEvent) { window.attachEvent('onload', fnc_onDomLoaded); } var gaJsHost = (("https:" == document.location.protocol) ? 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Oxford University Press
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Copyright © 2015 Oxford University Press
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1052-6773
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1745-6614
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jncimono;1999/26/31
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Abstract

We review case-control designs for studying gene associations in which relatives of case patients are used as control subjects. These designs have the advantage that they avoid the problem of population stratification that can lead to spurious associations with noncausal genes. We focus on designs that use sibling, cousin, or pseudosibling controls, the latter formed as the set of genotypes not transmitted to the case from his or her parents. We describe a common conditional likelihood framework for use in analyzing data from any of these designs and review what is known about the validity of the various design and analysis combinations for estimating the genetic relative risk. We also present comparisons of efficiency for each of the family-based designs relative to the standard population-control design in which unrelated controls are selected from the source population of cases. Because of overmatching on genotype, the use of sibling controls leads to estimates of genetic relative risk that are approximately half as efficient as those obtained with the use of population controls, while relative efficiency for cousin controls is approximately 90%. However, we find that, for a rare gene, the sibling-control design can lead to improved efficiency for estimating a G × E interaction effect. We also review some restricted designs that can substantially improve efficiency, e.g., restriction of the sample to case-sibling pairs with an affected parent. We conclude that family-based case-control studies are an attractive alternative to population-based case-control designs using unrelated control subjects. Oxford University Press « Previous | Next Article » Table of Contents This Article J Natl Cancer Inst Monogr (1999) 1999 (26): 31-37. This article appears in: Innovative Study Designs and Analytic Approaches to the Genetic Epidemiology of Cancer » Abstract Free Full Text (HTML) Free Full Text (PDF) Free Classifications II. GENE CHARACTERIZATION PANEL Services Article metrics Alert me when cited Alert me if corrected Find similar articles Similar articles in Web of Science Similar articles in PubMed Add to my archive Download citation Request Permissions Citing Articles Load citing article information Citing articles via CrossRef Citing articles via Scopus Citing articles via Web of Science Citing articles via Google Scholar Google Scholar Articles by Gauderman, W. J. Articles by Thomas, D. C. Search for related content PubMed PubMed citation Articles by Gauderman, W. J. Articles by Witte, J. S. Articles by Thomas, D. C. Related Content Load related web page information Share Email this article CiteULike Delicious Facebook Google+ Mendeley Twitter What's this? Search this journal: Advanced » Current Issue May 2015 2015 (51) Alert me to new issues The Journal About this journal Rights & Permissions We are mobile – find out more Journals Career Network Editor-in-Chief Carmen J. Allegra View the JNCI editorial board For Authors Instructions to authors Author Self Archiving Policy Alerting Services Email table of contents CiteTrack XML RSS feed Corporate Services Advertising sales Reprints var taxonomies = ("MED00300"); Most Most Read Clinical Practice Guidelines on the Use of Integrative Therapies as Supportive Care in Patients Treated for Breast Cancer Descriptive Review of the Literature on Breast Cancer Outcomes: 1990 Through 2000 Prevalence of Depression in Patients With Cancer Biology of Oral Mucosa and Esophagus Chapter 6: Estrogen Metabolism by Conjugation » View all Most Read articles Most Cited Chapter 1: Human Papillomavirus and Cervical Cancer--Burden and Assessment of Causality Chapter 4: Estrogens as Endogenous Genotoxic Agents--DNA Adducts and Mutations Prevalence of Depression in Patients With Cancer Preoperative Chemotherapy in Patients With Operable Breast Cancer: Nine-Year Results From National Surgical Adjuvant Breast and Bowel Project B-18 Overview of the Randomized Trials of Radiotherapy in Ductal Carcinoma In Situ of the Breast » View all Most Cited articles Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department. Online ISSN 1745-6614 - Print ISSN 1052-6773 Copyright © 2015 Oxford University Press Oxford Journals Oxford University Press Site Map Privacy Policy Cookie Policy Legal Notices Frequently Asked Questions Other Oxford University Press sites: Oxford University Press Oxford Journals China Oxford Journals Japan Academic & Professional books Children's & Schools Books Dictionaries & Reference Dictionary of National Biography Digital Reference English Language Teaching Higher Education Textbooks International Education Unit Law Medicine Music Online Products & Publishing Oxford Bibliographies Online Oxford Dictionaries Online Oxford English Dictionary Oxford Language Dictionaries Online Oxford Scholarship Online Reference Rights and Permissions Resources for Retailers & Wholesalers Resources for the Healthcare Industry Very Short Introductions World's Classics function fnc_onDomLoaded() { var query_context = getQueryContext(); PF_initOIUnderbar(query_context,":QS:default","","JRN"); PF_insertOIUnderbar(0); }; if (window.addEventListener) { window.addEventListener('load', fnc_onDomLoaded, false); } else if (window.attachEvent) { window.attachEvent('onload', fnc_onDomLoaded); } var gaJsHost = (("https:" == document.location.protocol) ? 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Journal

JNCI MonographsOxford University Press

Published: Dec 1, 1999

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