Association mapping for compound heterozygous traits using phenotypic distance and integer programming

Dan Gusfield; Rasmus Nielsen

doi:10.1007/978-3-662-48221-6_10

Association mapping for compound heterozygous traits using phenotypic distance and integer programming

^*Corresponding author for this work

Abstract

For many important complex traits, Genome Wide Association Studies (GWAS) have only recovered a small proportion of the variance in disease prevalence known to be caused by genetics. The most common explanation for this is the presence of multiple rare mutations that cannot be identified in GWAS due to a lack of statistical power. Such rare mutations may be concentrated in relatively few genes, as is the case for many known Mendelian diseases, where the mutations are often compound heterozygous (CH), defined below. Due to the multiple mutations, each of which contributes little by itself to the prevalence of the disease, GWAS also lacks power to identify genes contributing to a CH-trait. In this paper, we address the problem of finding genes that are causal for CH-traits, by introducing a discrete optimization problem, called the Phenotypic Distance Problem. We show that it can be efficiently solved on realistic-size simulated CH-data by using integer linear programming (ILP). The empirical results strongly validate this approach.

Original language	English
Title of host publication	Algorithms in Bioinformatics - 15th International Workshop, WABI 2015, Proceedings
Editors	Mihai Pop, Hélène Touzet
Number of pages	12
Publisher	Springer Verlag,
Publication date	1 Jan 2015
Pages	136-147
Article number	A1
ISBN (Print)	9783662482209
DOIs	https://doi.org/10.1007/978-3-662-48221-6_10
Publication status	Published - 1 Jan 2015
Event	15th International Workshop on Algorithms in Bioinformatics, WABI 2015 - Atlanta, United States Duration: 10 Sept 2015 → 12 Sept 2015

Conference

Conference	15th International Workshop on Algorithms in Bioinformatics, WABI 2015
Country/Territory	United States
City	Atlanta
Period	10/09/2015 → 12/09/2015
Sponsor	ACM Special Interest Group in Bioinformatics (ACM SIGBio), European Association for Theoretical Computer Science (EATCS), International Society for Computational Biology (ISCB)

Series	Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
Volume	9289
ISSN	0302-9743

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Association mapping for compound heterozygous traits using phenotypic distance and integer programming. / Gusfield, Dan; Nielsen, Rasmus.
Algorithms in Bioinformatics - 15th International Workshop, WABI 2015, Proceedings. ed. / Mihai Pop; Hélène Touzet. Springer Verlag, 2015. p. 136-147 A1 (Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics), Vol. 9289).

Research output: Chapter in Book/Report/Conference proceeding › Article in proceedings › Research › peer-review

Gusfield, D & Nielsen, R 2015, Association mapping for compound heterozygous traits using phenotypic distance and integer programming. in M Pop & H Touzet (eds), Algorithms in Bioinformatics - 15th International Workshop, WABI 2015, Proceedings., A1, Springer Verlag, Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics), vol. 9289, pp. 136-147, 15th International Workshop on Algorithms in Bioinformatics, WABI 2015, Atlanta, United States, 10/09/2015. https://doi.org/10.1007/978-3-662-48221-6_10

Gusfield D, Nielsen R. Association mapping for compound heterozygous traits using phenotypic distance and integer programming. In Pop M, Touzet H, editors, Algorithms in Bioinformatics - 15th International Workshop, WABI 2015, Proceedings. Springer Verlag,. 2015. p. 136-147. A1. (Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics), Vol. 9289). doi: 10.1007/978-3-662-48221-6_10

Gusfield, Dan ; Nielsen, Rasmus. / Association mapping for compound heterozygous traits using phenotypic distance and integer programming. Algorithms in Bioinformatics - 15th International Workshop, WABI 2015, Proceedings. editor / Mihai Pop ; Hélène Touzet. Springer Verlag, 2015. pp. 136-147 (Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics), Vol. 9289).

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Association mapping for compound heterozygous traits using phenotypic distance and integer programming

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