ParaHaplo 3.0: A program package for imputation and a haplotype-based whole-genome association study using hybrid parallel computing

Source Code for Biology and Medicine

Naoyuki Kamatani¹  Kazuharu Misawa² 

[1] Laboratory for Statistical Analysis, RIKEN Center for Genomic Medicine, Tokyo, Japan;Research Program for Computational Science, Research and Development Group for Next-Generation Integrated Living Matter Simulation, and Fusion of Data and Analysis Research and Development Team, RIKEN, 4-6-1 Shirokane-dai, Minato-ku, Tokyo 108-8639, Japan

关键词: GWAS;    HapMap;    parallel computing;    genotype imputation;    haplotype reconstruction;    ParaHaplo;   

Others  :  806477
DOI  :  10.1186/1751-0473-6-10

 received in 2011-02-28, accepted in 2011-05-24,  发布年份 2011

【 摘 要 】

Background

Use of missing genotype imputations and haplotype reconstructions are valuable in genome-wide association studies (GWASs). By modeling the patterns of linkage disequilibrium in a reference panel, genotypes not directly measured in the study samples can be imputed and used for GWASs. Since millions of single nucleotide polymorphisms need to be imputed in a GWAS, faster methods for genotype imputation and haplotype reconstruction are required.

Results

We developed a program package for parallel computation of genotype imputation and haplotype reconstruction. Our program package, ParaHaplo 3.0, is intended for use in workstation clusters using the Intel Message Passing Interface. We compared the performance of ParaHaplo 3.0 on the Japanese in Tokyo, Japan and Han Chinese in Beijing, and Chinese in the HapMap dataset. A parallel version of ParaHaplo 3.0 can conduct genotype imputation 20 times faster than a non-parallel version of ParaHaplo.

Conclusions

ParaHaplo 3.0 is an invaluable tool for conducting haplotype-based GWASs. The need for faster genotype imputation and haplotype reconstruction using parallel computing will become increasingly important as the data sizes of such projects continue to increase. ParaHaplo executable binaries and program sources are available at http://en.sourceforge.jp/projects/parallelgwas/releases/ webcite.

【 授权许可】

   
2011 Misawa and Kamatani; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Hirschhorn JN, Daly MJ: Genome-wide association studies for common diseases and complex traits. Nat Rev Genet 2005, 6(2):95-108.
• [2]Ozaki K, Ohnishi Y, Iida A, Sekine A, Yamada R, Tsunoda T, Sato H, Hori M, Nakamura Y, Tanaka T: Functional SNPs in the lymphotoxin-alpha gene that are associated with susceptibility to myocardial infarction. Nat Genet 2002, 32(4):650-654.
• [3]Onouchi Y, Gunji T, Burns JC, Shimizu C, Newburger JW, Yashiro M, Nakamura Y, Yanagawa H, Wakui K, Fukushima Y, Kishi F, Hamamoto K, Terai M, Sato Y, Ouchi K, Saji T, Nariai A, Kaburagi Y, Yoshikawa T, Suzuki K, Tanaka T, Nagai T, Cho H, Fujino A, Sekine A, Nakamichi R, Tsunoda T, Kawasaki T, Hata A: ITPKC functional polymorphism associated with Kawasaki disease susceptibility and formation of coronary artery aneurysms. Nat Genet 2008, 40(1):35-42.
• [4]Tokuhiro S, Yamada R, Chang X, Suzuki A, Kochi Y, Sawada T, Suzuki M, Nagasaki M, Ohtsuki M, Ono M, Furukawa H, Nagashima M, Yoshino S, Mabuchi A, Sekine A, Saito S, Takahashi A, Tsunoda T, Nakamura Y, Yamamoto K: An intronic SNP in a RUNX1 binding site of SLC22A4, encoding an organic cation transporter, is associated with rheumatoid arthritis. Nat Genet 2003, 35(4):341-348.
• [5]Misawa K, Kamatani N: ParaHaplo: A program package for haplotype-based whole-genome association study using parallel computing. Source Code Biol Med 2009, 4(1):7. BioMed Central Full Text
• [6]Misawa K, Kamatani N: ParaHaplo 2.0: a program package for haplotype-estimation and haplotype-based whole-genome association study using parallel computing. Source Code Biol Med 2010, 5(1):5. BioMed Central Full Text
• [7]Li Y, Willer C, Sanna S, Abecasis G: Genotype imputation. Annu Rev Genomics Hum Genet 2009, 10:387-406.
• [8]Marchini J, Howie B, Myers S, McVean G, Donnelly P: A new multipoint method for genome-wide association studies by imputation of genotypes. Nat Genet 2007, 39(7):906-913.
• [9]Nothnagel M, Ellinghaus D, Schreiber S, Krawczak M, Franke A: A comprehensive evaluation of SNP genotype imputation. Hum Genet 2009, 125(2):163-171.
• [10]Li Y, Abecasis GR: Mach 1.0: rapid haplotype reconstruction and missing genotype inference. Am J Hum Genet 2006, 79:S2290.
• [11]Culler DE, Gupta A, Singh JP: Parallel Computer Architecture: A Hardware/Software Approach. San Francisco, CA: Morgan Kaufmann Publishers; 1997.
• [12]The International HapMap Consortium: The International HapMap Project. Nature 2003, 426(6968):789-796.
• [13]Altshuler DM, Gibbs RA, Peltonen L, Dermitzakis E, Schaffner SF, Yu F, Bonnen PE, de Bakker PI, Deloukas P, Gabriel SB, Gwilliam R, Hunt S, Inouye M, Jia X, Palotie A, Parkin M, Whittaker P, Chang K, Hawes A, Lewis LR, Ren Y, Wheeler D, Muzny DM, Barnes C, Darvishi K, Hurles M, Korn JM, Kristiansson K, Lee C, McCarrol SA, et al.: Integrating common and rare genetic variation in diverse human populations. Nature 2010, 467(7311):52-58.
• [14]Marchini J, Cutler D, Patterson N, Stephens M, Eskin E, Halperin E, Lin S, Qin ZS, Munro HM, Abecasis GR, Donnelly P: A comparison of phasing algorithms for trios and unrelated individuals. Am J Hum Genet 2006, 78(3):437-450.
• [15]Nakamura Y: The BioBank Japan Project. Clin Adv Hematol Oncol 2007, 5(9):696-697.
• [16]Mardanov AV, Ravin NV, Kuznetsov BB, Samigullin TH, Antonov AS, Kolganova TV, Skyabin KG: Complete Sequence of the Duckweed (Lemna minor) Chloroplast Genome: Structural Organization and Phylogenetic Relationships to Other Angiosperms. J Mol Evol 2008.
• [17]SNPHAP - A program for estimating frequencies of large haplotypes of SNPs [http://www-gene.cimr.cam.ac.uk/clayton/software/] webcite
• [18]Rabenseifner R: Hybrid parallel programming on HPC platforms. The proceedings of the Fifth European Workshop on OpenMP, EWOMP 2003; Aachen, Germany 2003.
• [19]Gabriel SB, Schaffner SF, Nguyen H, Moore JM, Roy J, Blumenstiel B, Higgins J, DeFelice M, Lochner A, Faggart M, Liu-Cordero SN, Rotimi C, Adeyemo A, Cooper R, Ward R, Lander ES, Daly MJ, Altshuler D: The structure of haplotype blocks in the human genome. Science 2002, 296(5576):2225-2229.
• [20]Barrett JC, Fry B, Maller J, Daly MJ: Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 2005, 21(2):263-265.
• [21]Kamatani Y, Matsuda K, Okada Y, Kubo M, Hosono N, Daigo Y, Nakamura Y, Kamatani N: Genome-wide association study of hematological and biochemical traits in a Japanese population. Nat Genet 2010, 42(3):210-215.