title: Using affected sib-pairs to uncover rare disease variants.
abstract: OBJECTIVE
  We propose a new test for rare variant mapping, based on an affected sib-pair sample and a control sample. In each sib-pair, only the index case needs to be sequenced, and the number of alleles shared identical-by-descent between the sibs is used as complementary information. The test makes use of both association and linkage information. We compare this test to the Armitage test on case-control data, with cases either from the general population of cases or from a sample of cases having an affected sib.
  
  
  METHODS
  A score test based on the likelihood in a multiplicative risk model is proposed. Its power is estimated by simulations and compared to Armitage test's power.
  
  
  RESULTS
  The affected sib-pairs design allows a tremendous gain of power over the case-control design (from 1 to 99% for a moderate sample size and relative risk values around 3, at an α level of 10(-11)). When cases are ascertained in a sample of cases having an affected sib, the use of linkage information in our test allows a gain of power of more than 20% in certain situations.
  
  
  CONCLUSIONS
  We demonstrate the interest in using familial data and both association and linkage information for rare variant mapping.
authors.affiliation: Université Paris-Sud, Villejuif, France. herve.perdry@u-psud.fr
authors.forename: Hervé
authors.initials: H
authors.lastname: Perdry
authors.forename: Bertram
authors.initials: B
authors.lastname: Müller-Myhsok
authors.forename: Françoise
authors.initials: F
authors.lastname: Clerget-Darpoux
mesh_terms: D008040:Genetic Linkage; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008957:Models, Genetic; D015233:Models, Statistical; D035583:Rare Diseases / Q000235:genetics*; D035781:Siblings