Family‐based Association Test (FBAT)

Nan M Laird, Harvard School of Public Health, Boston, Massachusetts, USA

Published online: January 2011

DOI: 10.1002/9780470015902.a0022500

Abstract

Statistical tests of association are commonly used to confirm or exclude a relationship between disease and selected genes. Tests which are based on data from unrelated individuals are very popular, but can be biased if the sample contains individuals with different genetic ancestries. Family‐based Association tests avoid the problem of bias due to mixed ancestry by using within family comparisons. Many different family designs are possible, the most popular using parents and offspring, but others use just sibships. Dichotomous, measured and time‐to‐onset phenotypes can be accommodated. FBATs are generally less powerful than tests based on a sample of unrelated individuals, but special settings exist, for example testing for rare variants with affected offspring and their parents, where the family design has a power advantage.

Key Concepts:

  • Genetic tests based on population samples can be biased due to differing genetic ancestries.

  • Association designs using family members can avoid bias by using within family comparison.

  • The simplest family test is the TDT which uses affected offspring and their parents.

  • FBAT refers to a class of tests for family designs that can accommodate any type of genetic model, any phenotype and any family configuration, e.g. parents and their offspring, sibships or even general pedigrees.

  • In general, FBAT's are less powerful than their population‐based counter‐parts, and they generally also require more genotyping, but in some circumstances, e.g. for rare variants and in testing for gene–environment interactions, they can be more powerful.

Keywords: genetic association test; TDT; family design; trios; discordant sibship test; missing parents; Mendel's laws; linkage; linkage disequilibrium

Figure 1.

Transmissions of genetic variants from parents to offspring is governed by Mendel's First Law of Segregation. It forms the basis of the TDT.

Figure 2.

Using the Sufficient Statistic to calculate the distribution of offspring genotypes under different nuclear family configurations.
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Further Reading

Ewens WJ, Li M and Spielman RS (2008) A review of family based tests for linkage disequilibrium between a quantitative trait and a genetic marker. PLoS Genetics 4: e1000180.

McGinnis R, Shiftman S and Darvasi A (2002) Power and efficiency of the TDT and case‐control design for association scans. Behavioral Genetics 32: 135–144.

Risch N and Merikangas K (1996) The future of genetic studies of complex human diseases. Science 273: 1516–1517.

Related Sub-Topics:

Inter-Individual Variation and Polymorphism | Statistical Methodology in Genetics | Gene Mapping by Disease Association
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Article Title: Family‐based Association Test (FBAT)
 
How to Cite close
Laird, Nan M(Jan 2011) Family‐based Association Test (FBAT). In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0022500]