title: Fast pairwise IBD association testing in genome-wide association studies.
abstract: BACKGROUND
  Recently, investigators have proposed state-of-the-art Identity-by-descent (IBD) mapping methods to detect IBD segments between purportedly unrelated individuals. The IBD information can then be used for association testing in genetic association studies. One approach for this IBD association testing strategy is to test for excessive IBD between pairs of cases ('pairwise method'). However, this approach is inefficient because it requires a large number of permutations. Moreover, a limited number of permutations define a lower bound for P-values, which makes fine-mapping of associated regions difficult because, in practice, a much larger genomic region is implicated than the region that is actually associated.
  
  
  RESULTS
  In this article, we introduce a new pairwise method 'Fast-Pairwise'. Fast-Pairwise uses importance sampling to improve efficiency and enable approximation of extremely small P-values. Fast-Pairwise method takes only days to complete a genome-wide scan. In the application to the WTCCC type 1 diabetes data, Fast-Pairwise successfully fine-maps a known human leukocyte antigen gene that is known to cause the disease.
  
  
  BACKGROUND
  Fast-Pairwise is publicly available at: http://genetics.cs.ucla.edu/graphibd.
authors.affiliation: Division of Genetics, Brigham and Women's Hospital and Division of Rheumatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA, Partners Center for Personalized Genetic Medicine, Boston, MA 02115, USA, Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA, Computer Science Department, University of California, Los Angeles, CA 90095, USA, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands, Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands and Department of Human Genetics, University of California, Los Angeles, CA 90095, USA.
authors.forename: Buhm
authors.initials: B
authors.lastname: Han
authors.forename: Eun Yong
authors.initials: EY
authors.lastname: Kang
authors.forename: Soumya
authors.initials: S
authors.lastname: Raychaudhuri
authors.forename: Paul I W
authors.initials: PI
authors.lastname: de Bakker
authors.forename: Eleazar
authors.initials: E
authors.lastname: Eskin
mesh_terms: D000465:Algorithms; D016022:Case-Control Studies; D002874:Chromosome Mapping; D003198:Computer Simulation; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D019655:Quantitative Trait, Heritable
chemical_list: D006680:HLA Antigens