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Am. J. Hum. Genet. 70:920934, 2002 Quantitative-Trait Homozygosity and Association Mapping
 

Summary: Am. J. Hum. Genet. 70:920934, 2002
920
Quantitative-Trait Homozygosity and Association Mapping
and Empirical Genomewide Significance in Large, Complex
Pedigrees: Fasting Serum-Insulin Level in the Hutterites
Mark Abney,1,2
Carole Ober,1
and Mary Sara McPeek1,2
Departments of 1
Human Genetics and 2
Statistics, University of Chicago, Chicago
We present methods for linkage and association mapping of quantitative traits for a founder population with a
large, known genealogy. We detect linkage to quantitative-trait loci (QTLs) through a multipoint homozygosity-
mapping method. We propose two association methods, one of which is single point and uses a general two-allele
model and the other of which is multipoint and uses homozygosity by descent for a particular allele. In all three
methods, we make extensive use of the pedigree and genotype information, while keeping the computations simple
and efficient. To assess significance, we have developed a permutation-based test that takes into account the
covariance structure due to relatedness of individuals and can be used to determine empirical genomewide and
locus-specific P values. In the case of multivariate-normally distributed trait data, the permutation-based test is
asymptotically exact. The test is broadly applicable to a variety of mapping methods that fall within the class of

  

Source: Abney, Mark - Department of Human Genetics, University of Chicago

 

Collections: Computer Technologies and Information Sciences; Biology and Medicine