|Publication Type||Journal Article|
|Year of Publication||2014|
|Authors||Han, B, Kang, EYong, Raychaudhuri, S, de Bakker, PIW, Eskin, E|
|Date Published||2014 Jan 15|
|Keywords||Algorithms, Case-Control Studies, Chromosome Mapping, Computer Simulation, Diabetes Mellitus, Type 1, Genome, Human, Genome-Wide Association Study, HLA Antigens, Humans, Polymorphism, Single Nucleotide, Quantitative Trait, Heritable|
MOTIVATION: 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.
AVAILABILITY: Fast-Pairwise is publicly available at: http://genetics.cs.ucla.edu/graphibd.
|PubMed Central ID||PMC3892684|
|Grant List||1R01AR062886-01 / AR / NIAMS NIH HHS / United States |
U01 HG007033 / HG / NHGRI NIH HHS / United States
U01-DA024417 / DA / NIDA NIH HHS / United States
K25 HL080079 / HL / NHLBI NIH HHS / United States
P01 HL028481 / HL / NHLBI NIH HHS / United States
U01 DA024417 / DA / NIDA NIH HHS / United States
P01-HL28481 / HL / NHLBI NIH HHS / United States
K25-HL080079 / HL / NHLBI NIH HHS / United States
R01 AR063759 / AR / NIAMS NIH HHS / United States
R01 AR062886 / AR / NIAMS NIH HHS / United States
R01 ES022282 / ES / NIEHS NIH HHS / United States
P01 HL030568 / HL / NHLBI NIH HHS / United States
P01-HL30568 / HL / NHLBI NIH HHS / United States