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Erschienen in: BMC Proceedings 7/2016

Open Access 01.10.2016 | Proceedings

A LASSO penalized regression approach for genome-wide association analyses using related individuals: application to the Genetic Analysis Workshop 19 simulated data

verfasst von: Charalampos Papachristou, Carole Ober, Mark Abney

Erschienen in: BMC Proceedings | Sonderheft 7/2016

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Abstract

We propose a novel LASSO (least absolute shrinkage and selection operator) penalized regression method used to analyze samples consisting of (potentially) related individuals. Developed in the context of linear mixed models, our method models the relatedness of individuals in the sample through a random effect whose covariance structure is a linear function of known matrices with elements combinations of the condensed coefficients of identity between the individuals in the sample. We implement our method to analyze the simulated family data provided by the 19th Genetic Analysis Workshop in an effort to identify loci regulating the simulated trait of systolic blood pressure. The analyses were performed with full knowledge of the simulation model. Our findings demonstrate that we can significantly reduce the rate of false positive signals by incorporating the relatedness of the study participants.
Literatur
1.
Zurück zum Zitat Kang HM, Sul JH, Service SK, Zaitlen NA, Kong SY, Freimer NB, et al. Variance component model to account for sample structure in genome-wide association studies. Nat Genet. 2010;42(4):348–54.CrossRefPubMedPubMedCentral Kang HM, Sul JH, Service SK, Zaitlen NA, Kong SY, Freimer NB, et al. Variance component model to account for sample structure in genome-wide association studies. Nat Genet. 2010;42(4):348–54.CrossRefPubMedPubMedCentral
2.
Zurück zum Zitat Fusi N, Lippert C, Lawrence ND, Stegle O. Warped linear mixed models for the genetic analysis of transformed phenotypes. Nat Commun. 2014;5:4890.CrossRefPubMedPubMedCentral Fusi N, Lippert C, Lawrence ND, Stegle O. Warped linear mixed models for the genetic analysis of transformed phenotypes. Nat Commun. 2014;5:4890.CrossRefPubMedPubMedCentral
4.
Zurück zum Zitat Papachristou C, Lin S. A confidence set inference method for identifying SNPs that regulate quantitative phenotypes. Hum Hered. 2012;73(3):174–83.CrossRefPubMed Papachristou C, Lin S. A confidence set inference method for identifying SNPs that regulate quantitative phenotypes. Hum Hered. 2012;73(3):174–83.CrossRefPubMed
5.
Zurück zum Zitat Waldmann P, Mészáros G, Gredler B, Fuerst C, Sölkner J. Evaluation of the lasso and the elastic net in genome-wide association studies. Front Genet. 2013;4:270.CrossRefPubMedPubMedCentral Waldmann P, Mészáros G, Gredler B, Fuerst C, Sölkner J. Evaluation of the lasso and the elastic net in genome-wide association studies. Front Genet. 2013;4:270.CrossRefPubMedPubMedCentral
6.
Zurück zum Zitat Tibshirani R. Regression shrinkage and selection via the lasso. J R Stat Soc Series B Stat Methodol. 1996;58(1):267–88. Tibshirani R. Regression shrinkage and selection via the lasso. J R Stat Soc Series B Stat Methodol. 1996;58(1):267–88.
7.
Zurück zum Zitat Ding X, Su S, Nandakumar K, Wang X, Fardo DW. A 2-step penalized regression method for family-based next-generation sequencing association studies. BMC Proc. 2014;8 Suppl 1:S25.CrossRefPubMedPubMedCentral Ding X, Su S, Nandakumar K, Wang X, Fardo DW. A 2-step penalized regression method for family-based next-generation sequencing association studies. BMC Proc. 2014;8 Suppl 1:S25.CrossRefPubMedPubMedCentral
8.
Zurück zum Zitat Schelldorfer J, Bühlmann P, van de Geer S. Estimation for high-dimensional linear mixed-effects models using L1-penalization. Scand Stat Theory Appl. 2011;38(2):197–214.CrossRef Schelldorfer J, Bühlmann P, van de Geer S. Estimation for high-dimensional linear mixed-effects models using L1-penalization. Scand Stat Theory Appl. 2011;38(2):197–214.CrossRef
9.
Zurück zum Zitat Blangero J, Teslovich TM, Sim X, Almeida MA, Jun G, Dyer TD, Johnson M, Peralta JM, Manning AK, Wood AR, et al. Omics squared: human genomic, transcriptomic, and phenotypic data for Genetic Analysis Workshop 19. BMC Proc. 2015;9 Suppl 8:S2. Blangero J, Teslovich TM, Sim X, Almeida MA, Jun G, Dyer TD, Johnson M, Peralta JM, Manning AK, Wood AR, et al. Omics squared: human genomic, transcriptomic, and phenotypic data for Genetic Analysis Workshop 19. BMC Proc. 2015;9 Suppl 8:S2.
10.
11.
Zurück zum Zitat Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, et al. PLINK: a toolset for whole-genome association and population-based linkage analysis. Am J Hum Genet. 2007;81(3):559–75.CrossRefPubMedPubMedCentral Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, et al. PLINK: a toolset for whole-genome association and population-based linkage analysis. Am J Hum Genet. 2007;81(3):559–75.CrossRefPubMedPubMedCentral
Metadaten
Titel
A LASSO penalized regression approach for genome-wide association analyses using related individuals: application to the Genetic Analysis Workshop 19 simulated data
verfasst von
Charalampos Papachristou
Carole Ober
Mark Abney
Publikationsdatum
01.10.2016
Verlag
BioMed Central
Erschienen in
BMC Proceedings / Ausgabe Sonderheft 7/2016
Elektronische ISSN: 1753-6561
DOI
https://doi.org/10.1186/s12919-016-0034-9

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