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778 The American Journal of Human Genetics Volume 78 May 2006 www.ajhg.org Efficient Study Designs for Test of Genetic Association Using Sibship Data
 

Summary: 778 The American Journal of Human Genetics Volume 78 May 2006 www.ajhg.org
Efficient Study Designs for Test of Genetic Association Using Sibship Data
and Unrelated Cases and Controls
Mingyao Li,1,2
Michael Boehnke,2
and Gonc¸alo R. Abecasis2
1
Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia; and 2
Department of
Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor
Linkage mapping of complex diseases is often followed by association studies between phenotypes and marker
genotypes through use of case-control or family-based designs. Given fixed genotyping resources, it is important to
know which study designs are the most efficient. To address this problem, we extended the likelihood-based method
of Li et al., which assesses whether there is linkage disequilibrium between a disease locus and a SNP, to accommodate
sibships of arbitrary size and disease-phenotype configuration. A key advantage of our method is the ability to
combine data from different family structures. We consider scenarios for which genotypes are available for unrelated
cases, affected sib pairs (ASPs), or only one sibling per ASP. We construct designs that use cases only and others
that use unaffected siblings or unrelated unaffected individuals as controls. Different combinations of cases and
controls result in seven study designs. We compare the efficiency of these designs when the number of individuals
to be genotyped is fixed. Our results suggest that (1) when the disease is influenced by a single gene, the one sibling

  

Source: Abecasis, Goncalo - Department of Biostatistics, University of Michigan
Pennsylvania, University of - Center for Clinical Epidemiology and Biostatistics

 

Collections: Biology and Medicine; Mathematics