Dataset Information

Sufficient direction factor model and its application to gene expression quantitative trait loci discovery.

ABSTRACT: Rapid improvement in technology has made it relatively cheap to collect genetic data, however statistical analysis of existing data is still much cheaper. Thus, secondary analysis of single-nucleotide polymorphism, SNP, data, i.e., reanalysing existing data in an effort to extract more information, is an attractive and cost-effective alternative to collecting new data. We study the relationship between gene expression and SNPs through a combination of factor analysis and dimension reduction estimation. To take advantage of the flexibility in traditional factor models where the latent factors are not required to be normal, we recommend using semiparametric sufficient dimension reduction methods in the joint estimation of the combined model. The resulting estimator is flexible and has superior performance relative to the existing estimator, which relies on additional assumptions on the latent factors. We quantify the asymptotic performance of the proposed parameter estimator and perform inference by assessing the estimation variability and by constructing confidence intervals. The new results enable us to identify, for the first time, statistically significant SNPs concerning gene-SNP relations in lung tissue from genotype-tissue expression data.

SUBMITTER: Jiang F

PROVIDER: S-EPMC6508038 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Sufficient direction factor model and its application to gene expression quantitative trait loci discovery.

Jiang F F Ma Y Y Wei Y Y

Biometrika 20190422 2

Rapid improvement in technology has made it relatively cheap to collect genetic data, however statistical analysis of existing data is still much cheaper. Thus, secondary analysis of single-nucleotide polymorphism, SNP, data, i.e., reanalysing existing data in an effort to extract more information, is an attractive and cost-effective alternative to collecting new data. We study the relationship between gene expression and SNPs through a combination of factor analysis and dimension reduction esti ...[more]

PMID: 31097835

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Project description:Genetic dissection of the S rat genome has provided strong evidence for the presence of two interacting blood pressure (BP) quantitative trait loci (QTLs), termed QTL1 and QTL2, on rat chromosome 5. However, the identities of the underlying interacting genetic factors remain unknown. Further experiments targeted to identify the interacting genetic factors by the substitution mapping approach alone are difficult because of the interdependency of natural recombinations to occur at the two QTLs. We hypothesized that the interacting genetic factors underlying these two QTLs may interact at the level of gene transcription and thereby represent expression QTLs (eQTLs). To detect these interacting eQTLs, a custom QTL chip containing the annotated genes within QTL1 and QTL2 was developed and used to conduct a transcriptional profiling study of S and two congenic strains that retain either one or both the QTLs. The results uncovered an interaction between two transcription factors, DMRTA2 and NFIA. Further, the âbiological signatureâ elicited by these two transcription factors was differential between the congenic strain that retained LEW alleles at both QTL1 and 2 compared to the congenic strain that retained LEW alleles at QTL1 alone. A network of transcription factors potentially affecting BP could be traced, lending support to our hypothesis. Pairs of Cy5 and Cy3 labeled targets were co-hybridized onto either a custom long oligonucleotide microarray for the interrogation of 231 genes encompassed by QTL1 and QTL2, or a TIGR rat cDNA array consisting of 26,401 probe elements representing 20,465 unique non-QTL genes. A âflip-dyeâ or âbalanced blockâ design was used as the experimental method of choice to account for potential dye-bias labeling effects. Six âbalanced blockâ normalized files are submitted for the long oligonucleotide array interrogating the hearts from S versus S.LEW(5)x6x9 animals, fourteen âflip-dyeâ hybridizations are submitted for the cDNA array interrogating the hearts from S versus S.LEW(5)x6x9 animals, and twelve âflip-dyeâ hybridizations are submitted for the cDNA array interrogating the hearts from S versus S.LEW(5)x6x11 animals. GPR and MEV files cannot be located.

Dataset Information

Sufficient direction factor model and its application to gene expression quantitative trait loci discovery.

Publications

Sufficient direction factor model and its application to gene expression quantitative trait loci discovery.

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