Family-Based Association Studies

  • Kui ZhangEmail author
  • Hongyu Zhao


Over the past decade, association studies based on linkage disequilibrium have become increasingly popular for detecting genetic variations underlying complex human diseases because association-based methods have been shown to have more power than traditional linkage-based methods in theoretical and empirical studies. There are two general designs in association studies: family-based designs that use pedigrees and population-based designs that use unrelated individuals. Although population-based designs are generally more powerful than family-based designs, and the recruitment of unrelated individuals is easier than the recruitment of families, they are subject to bias in the presence of population stratification. As a compromise between linkage studies and population-based association studies, family-based association designs can have similar power with population-based designs and are robust in the presence of population stratification. Therefore, family-based association designs have received great attention recently. In this chapter, we first review methods that can analyze the simplest family-based association design with one affected offspring with its two parents, all genotyped at a bi-allelic marker locus. We then discuss its various extensions that can increase power and utilize multi-allelic markers, families with multiple siblings, families with incomplete parental genotypes, quantitative traits, and multiple tightly linked markers. The association methods using family-based designs can be broadly classified into two groups: nonparametric methods based on the allele counting and parametric methods based on the likelihood function. Although these methods result in similar test statistics for the simplest family-based association design with one affected offspring with its two parents, their extensions on more complex situations vary greatly. Further developments of statistical methods to utilize general pedigrees and to detect gene–environment interactions are also discussed. Finally, we conclude this review by listing the available software packages that can carry out the analysis of family-based association designs and illustrating some of them based on a real data set.


Parental Genotype Transmission Disequilibrium Test Affected Offspring General Pedigree Disease Susceptibility Locus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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We are grateful to the authors of reference [24] for the use of the Oxford ACE data, which is available on request from Dr. Martin Farrall ( This work was supported in part by the grants NIH GM074913 (KZ) and GM59507 (HZ) from the National Institute of General Medical Sciences.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  1. 1.Section on Statistical GeneticsDepartment of Biostatistics University of Alabama at BirminghamBirminghamUSA
  2. 2.Department of Epidemiology and Public HealthYale University School of MedicineNew HavenUSA

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