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www.ajhg.org The American Journal of Human Genetics Volume 81 November 2007 913 Family-Based Association Tests for Genomewide Association Scans
 

Summary: www.ajhg.org The American Journal of Human Genetics Volume 81 November 2007 913
ARTICLE
Family-Based Association Tests for Genomewide Association Scans
Wei-Min Chen and Gonc¸alo R. Abecasis
With millions of single-nucleotide polymorphisms (SNPs) identified and characterized, genomewide association studies
have begun to identify susceptibility genes for complex traits and diseases. These studies involve the characterization
and analysis of very-high-resolution SNP genotype data for hundreds or thousands of individuals. We describe a com-
putationally efficient approach to testing association between SNPs and quantitative phenotypes, which can be applied
to whole-genome association scans. In addition to observed genotypes, our approach allows estimation of missing
genotypes, resulting in substantial increases in power when genotyping resources are limited. We estimate missing
genotypes probabilistically using the Lander-Green or Elston-Stewart algorithms and combine high-resolution SNP ge-
notypes for a subset of individuals in each pedigree with sparser marker data for the remaining individuals. We show
that power is increased whenever phenotype information for ungenotyped individuals is included in analyses and that
high-density genotyping of just three carefully selected individuals in a nuclear family can recover 190% of the infor-
mation available if every individual were genotyped, for a fraction of the cost and experimental effort. To aid in study
design, we evaluate the power of strategies that genotype different subsets of individuals in each pedigree and make
recommendations about which individuals should be genotyped at a high density. To illustrate our method, we performed
genomewide association analysis for 27 gene-expression phenotypes in 3-generation families (Centre d'Etude du Poly-
morphisme Humain pedigrees), in which genotypes for 860,000 SNPs in 90 grandparents and parents are complemented
by genotypes for 6,700 SNPs in a total of 168 individuals. In addition to increasing the evidence of association at 15

  

Source: Abecasis, Goncalo - Department of Biostatistics, University of Michigan

 

Collections: Biology and Medicine; Mathematics