From phenotype to genotype: An association study of longitudinal phenotypic markers to alzheimer's disease relevant SNPs

Hua Wang, Feiping Nie, Heng Huang, Jingwen Yan, Sungeun Kim, Kwangsik Nho, Shannon L. Risacher, Andrew Saykin, Li Shen

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Motivation: Imaging genetic studies typically focus on identifying single-nucleotide polymorphism (SNP) markers associated with imaging phenotypes. Few studies perform regression of SNP values on phenotypic measures for examining how the SNP values change when phenotypic measures are varied. This alternative approach may have a potential to help us discover important imaging genetic associations from a different perspective. In addition, the imaging markers are often measured over time, and this longitudinal profile may provide increased power for differentiating genotype groups. How to identify the longitudinal phenotypic markers associated to disease sensitive SNPs is an important and challenging research topic. Results: Taking into account the temporal structure of the longitudinal imaging data and the interrelatedness among the SNPs, we propose a novel 'task-correlated longitudinal sparse regression' model to study the association between the phenotypic imaging markers and the genotypes encoded by SNPs. In our new association model, we extend the widely used ℓ2,1-norm for matrices to tensors to jointly select imaging markers that have common effects across all the regression tasks and time points, and meanwhile impose the trace-norm regularization onto the unfolded coefficient tensor to achieve low rank such that the interrelationship among SNPs can be addressed. The effectiveness of our method is demonstrated by both clearly improved prediction performance in empirical evaluations and a compact set of selected imaging predictors relevant to disease sensitive SNPs.

Original languageEnglish
Article numberbts411
JournalBioinformatics
Volume28
Issue number18
DOIs
StatePublished - Sep 2012

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Alzheimer's Disease
Genotype
Phenotype
Single Nucleotide Polymorphism
Longitudinal Studies
Alzheimer Disease
Imaging
Imaging techniques
Single nucleotide Polymorphism
Nucleotides
Polymorphism
Tensors
Tensor
Regression
Association Model
Genetic Association
Norm
Performance Prediction
Compact Set
Predictors

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Computational Theory and Mathematics
  • Computer Science Applications
  • Computational Mathematics
  • Statistics and Probability
  • Medicine(all)

Cite this

From phenotype to genotype : An association study of longitudinal phenotypic markers to alzheimer's disease relevant SNPs. / Wang, Hua; Nie, Feiping; Huang, Heng; Yan, Jingwen; Kim, Sungeun; Nho, Kwangsik; Risacher, Shannon L.; Saykin, Andrew; Shen, Li.

In: Bioinformatics, Vol. 28, No. 18, bts411, 09.2012.

Research output: Contribution to journalArticle

Wang, Hua ; Nie, Feiping ; Huang, Heng ; Yan, Jingwen ; Kim, Sungeun ; Nho, Kwangsik ; Risacher, Shannon L. ; Saykin, Andrew ; Shen, Li. / From phenotype to genotype : An association study of longitudinal phenotypic markers to alzheimer's disease relevant SNPs. In: Bioinformatics. 2012 ; Vol. 28, No. 18.
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