A generalized sparse regression model with adjustment of pedigree structure for variant detection from next generation sequencing data

  • Authors:
  • Shaolong Cao;Huaizhen Qin;Hong-Wen Deng;Yu-Ping Wang

  • Affiliations:
  • Department of Biomedical Engineering & Center for Bioinformatics and Genomics, Tulane University, New Orleans, LA, (504) 453-5259;Department of Biostatistics and Bioinformatics & Center for Bioinformatics and Genomics, Tulane University, New Orleans, LA, (504) 988-2042;Department of Biostatistics and Bioinformatics & Center for Bioinformatics and Genomics, Tulane University, New Orleans, LA, (504) 988-5164;Department of Biomedical Engineering & Center for Bioinformatics and Genomics, Tulane University, New Orleans, LA, (504) 865-5867

  • Venue:
  • Proceedings of the International Conference on Bioinformatics, Computational Biology and Biomedical Informatics
  • Year:
  • 2013

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Abstract

Next-generation sequencing technologies have been providing more comprehensive descriptions of rare and common sequence variants. Many powerful association tests have been developed for identifying significant individual common variants and genetic regions likely harboring rare and common variants. Single marker tests bear poor statistical powers to identify rare variant associations. Set-based tests sacrifice single marker resolution and require the set size to be much smaller than the sample size. Existing sparse regression algorithms can identify susceptible variants from a large set, even if its size far exceeds the sample size. Such algorithms are developed for analyzing sequence data of unrelated individuals and thus can be invalid in the presence of relatedness. Relatedness and population structure are two ubiquitous confounders in sequencing studies, especially those of admixed minorities. We hereby propose a flexible sparse regression model to jointly rectify relatedness, population structure and traditional covariates. Under this framework, we develop unweighted and weighted Lp (0