SEQCHIP: a powerful method to integrate sequence and genotype data for the detection of rare variant associations.

Bioinformatics
Dajiang J Liu, Suzanne M Leal

Abstract

Next-generation sequencing greatly increases the capacity to detect rare-variant complex-trait associations. However, it is still expensive to sequence a large number of samples and therefore often small datasets are used. Given cost constraints, a potentially more powerful two-step strategy is to sequence a subset of the sample to discover variants, and genotype the identified variants in the remaining sample. If only cases are sequenced, directly combining sequence and genotype data will lead to inflated type-I errors in rare-variant association analysis. Although several methods have been developed to correct for the bias, they are either underpowered or theoretically invalid. We proposed a new method SEQCHIP to integrate genotype and sequence data, which can be used with most existing rare-variant tests. It is demonstrated using both simulated and real datasets that the SEQCHIP method has controlled type-I errors, and is substantially more powerful than all other currently available methods. SEQCHIP is implemented in an R-Package and is available at http://linkage.rockefeller.edu/suzanne/seqchip/Seqchip.html.

References

Sep 2, 1998·Proceedings of the National Academy of Sciences of the United States of America·I M FraylingI P Tomlinson
Aug 7, 2004·Science·Jonathan C CohenHelen H Hobbs
Aug 18, 2004·Trends in Genetics : TIG·Marcus R Munafò, Jonathan Flint
Nov 3, 2004·Proceedings of the National Academy of Sciences of the United States of America·Nicola S FearnheadWalter F Bodmer
Feb 2, 2006·Proceedings of the National Academy of Sciences of the United States of America·Jonathan C CohenHelen H Hobbs
Mar 16, 2007·American Journal of Human Genetics·Gregory V KryukovShamil R Sunyaev
Mar 16, 2007·American Journal of Human Genetics·Nadav AhituvLen A Pennacchio
May 30, 2008·Nature Genetics·Walter Bodmer, Carolina Bonilla
Dec 6, 2008·PLoS Genetics·Yongtao Guan, Matthew Stephens
Dec 17, 2008·The Journal of Clinical Investigation·Stefano RomeoJonathan C Cohen
Feb 10, 2009·Proceedings of the National Academy of Sciences of the United States of America·Gregory V KryukovShamil R Sunyaev
Feb 14, 2009·PLoS Genetics·Bo Eskerod Madsen, Sharon R Browning
Oct 8, 2009·Genetic Epidemiology·Andrew P Morris, Eleftheria Zeggini
May 18, 2010·American Journal of Human Genetics·Alkes L PriceShamil R Sunyaev
Oct 27, 2010·PLoS Computational Biology·Gaurav BhatiaVineet Bafna
Nov 9, 2010·Genetic Epidemiology·Yun LiGonçalo R Abecasis
Dec 7, 2010·American Journal of Human Genetics·Dajiang J Liu, Suzanne M Leal
Mar 17, 2011·PLoS Genetics·Benjamin M NealeMark J Daly
Jun 28, 2011·Bioinformatics·Todd L EdwardsChun Li
Jul 9, 2011·American Journal of Human Genetics·Michael C WuXihong Lin
Jul 20, 2011·Genetic Epidemiology·Saonli Basu, Wei Pan
Oct 25, 2011·Nature Genetics·Soumya RaychaudhuriJohanna M Seddon

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