Analysis of familial aggregation studies with complex ascertainment schemes

Abigail G. Matthews, Dianne M. Finkelstein, Rebecca Betensky

Research output: Contribution to journalArticle

Abstract

Familial aggregation studies are a common first step in the identification of genetic determinants of disease. If aggregation is found, more refined genetic studies may be undertaken. Complex ascertainment schemes are frequently employed to ensure that the sample contains a sufficient number of families with multiple affected members, as required to detect aggregation. For example, an eligibility criterion for a family might be that both the mother and daughter have disease. Adjustments must be made for ascertainment to avoid bias. We propose adjusting for complex ascertainment schemes through a joint model for the outcomes of disease and ascertainment. This approach improves upon previous simplifying assumptions regarding the ascertainment process.

Original languageEnglish (US)
Pages (from-to)5076-5092
Number of pages17
JournalStatistics in Medicine
Volume27
Issue number24
DOIs
StatePublished - Dec 30 2008

Fingerprint

Aggregation
Inborn Genetic Diseases
Joint Model
Joints
Adjustment
Determinant
Sufficient
Family

Keywords

  • Ascertainment bias
  • Familial aggregation
  • Quadratic exponential model

ASJC Scopus subject areas

  • Epidemiology
  • Statistics and Probability

Cite this

Analysis of familial aggregation studies with complex ascertainment schemes. / Matthews, Abigail G.; Finkelstein, Dianne M.; Betensky, Rebecca.

In: Statistics in Medicine, Vol. 27, No. 24, 30.12.2008, p. 5076-5092.

Research output: Contribution to journalArticle

Matthews, Abigail G. ; Finkelstein, Dianne M. ; Betensky, Rebecca. / Analysis of familial aggregation studies with complex ascertainment schemes. In: Statistics in Medicine. 2008 ; Vol. 27, No. 24. pp. 5076-5092.
@article{bc4f496ee99440728e346264d321ae45,
title = "Analysis of familial aggregation studies with complex ascertainment schemes",
abstract = "Familial aggregation studies are a common first step in the identification of genetic determinants of disease. If aggregation is found, more refined genetic studies may be undertaken. Complex ascertainment schemes are frequently employed to ensure that the sample contains a sufficient number of families with multiple affected members, as required to detect aggregation. For example, an eligibility criterion for a family might be that both the mother and daughter have disease. Adjustments must be made for ascertainment to avoid bias. We propose adjusting for complex ascertainment schemes through a joint model for the outcomes of disease and ascertainment. This approach improves upon previous simplifying assumptions regarding the ascertainment process.",
keywords = "Ascertainment bias, Familial aggregation, Quadratic exponential model",
author = "Matthews, {Abigail G.} and Finkelstein, {Dianne M.} and Rebecca Betensky",
year = "2008",
month = "12",
day = "30",
doi = "10.1002/sim.3327",
language = "English (US)",
volume = "27",
pages = "5076--5092",
journal = "Statistics in Medicine",
issn = "0277-6715",
publisher = "John Wiley and Sons Ltd",
number = "24",

}

TY - JOUR

T1 - Analysis of familial aggregation studies with complex ascertainment schemes

AU - Matthews, Abigail G.

AU - Finkelstein, Dianne M.

AU - Betensky, Rebecca

PY - 2008/12/30

Y1 - 2008/12/30

N2 - Familial aggregation studies are a common first step in the identification of genetic determinants of disease. If aggregation is found, more refined genetic studies may be undertaken. Complex ascertainment schemes are frequently employed to ensure that the sample contains a sufficient number of families with multiple affected members, as required to detect aggregation. For example, an eligibility criterion for a family might be that both the mother and daughter have disease. Adjustments must be made for ascertainment to avoid bias. We propose adjusting for complex ascertainment schemes through a joint model for the outcomes of disease and ascertainment. This approach improves upon previous simplifying assumptions regarding the ascertainment process.

AB - Familial aggregation studies are a common first step in the identification of genetic determinants of disease. If aggregation is found, more refined genetic studies may be undertaken. Complex ascertainment schemes are frequently employed to ensure that the sample contains a sufficient number of families with multiple affected members, as required to detect aggregation. For example, an eligibility criterion for a family might be that both the mother and daughter have disease. Adjustments must be made for ascertainment to avoid bias. We propose adjusting for complex ascertainment schemes through a joint model for the outcomes of disease and ascertainment. This approach improves upon previous simplifying assumptions regarding the ascertainment process.

KW - Ascertainment bias

KW - Familial aggregation

KW - Quadratic exponential model

UR - http://www.scopus.com/inward/record.url?scp=59849120400&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=59849120400&partnerID=8YFLogxK

U2 - 10.1002/sim.3327

DO - 10.1002/sim.3327

M3 - Article

VL - 27

SP - 5076

EP - 5092

JO - Statistics in Medicine

JF - Statistics in Medicine

SN - 0277-6715

IS - 24

ER -