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Sex, age and generation effects on genome-wide linkage analysis of gene expression in transformed lymphoblasts.

Rangrej J, Beyene J, Hu P, Paterson AD - BMC Proc (2007)

Bottom Line: When generation was included in the model with age, all but 6 of the GEE age effects were no longer significant.However, there were minimal changes in the linkage results.The effect of age on linkage analyses was apparent for the expression of many genes, which appear to be mostly due to differences between the generations.

View Article: PubMed Central - HTML - PubMed

Affiliation: Programs in Genetics and Genome Biology, The Hospital for Sick Children, 101 College Street, TMDT East Tower, Toronto, Ontario M5G 1X8 Canada. jrangrej@sickkids.ca

ABSTRACT

Background: Many traits differ by age and sex in humans, but genetic analysis of gene expression has typically not included them in the analysis.

Methods: We used Genetic Analysis Workshop 15 Problem 1 data to determine whether gene expression in lymphoblasts showed differences by age and/or sex using generalized estimating equations (GEE). We performed quantitative trait linkage analysis of these genes including age and sex as covariates to determine whether the linkage results changed when they were included as covariates. Because the families included in the study all contain three generations, we also determined what effect inclusion of generation in the model had on the age effects.

Results: When controlling the false-discovery rate at 1%, using GEE we identified 30 transcripts that showed significant differences in expression by sex, while 1950 transcripts showed differences in expression associated with age. When subjected to linkage analysis, there were 37 linkages that disappeared, while 17 appeared when sex was included as a covariate. All these genes were, as expected, on the sex chromosomes. In contrast, when age was included in the linkage analysis, 462 linkage signals were no longer significant, while 223 became significant. When generation was included in the model with age, all but 6 of the GEE age effects were no longer significant. However, there were minimal changes in the linkage results.

Conclusion: The effect of age on linkage analyses was apparent for the expression of many genes, which appear to be mostly due to differences between the generations.

No MeSH data available.


Distribution of the number of gene expressions that are significant in the GEE model for the range of q-values. A, Covariates are sex and age; B, sex, age, and grandparental (gen1) and parental (gen2) generation.
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Figure 1: Distribution of the number of gene expressions that are significant in the GEE model for the range of q-values. A, Covariates are sex and age; B, sex, age, and grandparental (gen1) and parental (gen2) generation.

Mentions: Descriptive information regarding age and sex are provided in Table 1. From the GEE analysis of gene expression data, Figure 1A shows the distribution of the number of significant tests if different q-value thresholds are used for the models with age, sex, and generation. After adjustment for familial correlation there were 30 genes that showed significant differences by sex, compared to 1950 genes that were significantly associated with age (an FDR threshold of 0.01 was used). The respective p-values for test of significance were 0.000097 for sex and 0.023 for age. When generation was included in the model (Fig. 1B) only 6 of the age effects remained significant, while generation effects were significant for 277 and 862 genes, for the indicators for the grandparental (g1) and parental (g2) generations respectively (the number of genes with sex effects (29) remained similar). The p-values for this model were: sex = 8.1 × 10-5, age = 1.6 × 10-5, g1 = 0.0014, and g2 = 0.0053.


Sex, age and generation effects on genome-wide linkage analysis of gene expression in transformed lymphoblasts.

Rangrej J, Beyene J, Hu P, Paterson AD - BMC Proc (2007)

Distribution of the number of gene expressions that are significant in the GEE model for the range of q-values. A, Covariates are sex and age; B, sex, age, and grandparental (gen1) and parental (gen2) generation.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2367486&req=5

Figure 1: Distribution of the number of gene expressions that are significant in the GEE model for the range of q-values. A, Covariates are sex and age; B, sex, age, and grandparental (gen1) and parental (gen2) generation.
Mentions: Descriptive information regarding age and sex are provided in Table 1. From the GEE analysis of gene expression data, Figure 1A shows the distribution of the number of significant tests if different q-value thresholds are used for the models with age, sex, and generation. After adjustment for familial correlation there were 30 genes that showed significant differences by sex, compared to 1950 genes that were significantly associated with age (an FDR threshold of 0.01 was used). The respective p-values for test of significance were 0.000097 for sex and 0.023 for age. When generation was included in the model (Fig. 1B) only 6 of the age effects remained significant, while generation effects were significant for 277 and 862 genes, for the indicators for the grandparental (g1) and parental (g2) generations respectively (the number of genes with sex effects (29) remained similar). The p-values for this model were: sex = 8.1 × 10-5, age = 1.6 × 10-5, g1 = 0.0014, and g2 = 0.0053.

Bottom Line: When generation was included in the model with age, all but 6 of the GEE age effects were no longer significant.However, there were minimal changes in the linkage results.The effect of age on linkage analyses was apparent for the expression of many genes, which appear to be mostly due to differences between the generations.

View Article: PubMed Central - HTML - PubMed

Affiliation: Programs in Genetics and Genome Biology, The Hospital for Sick Children, 101 College Street, TMDT East Tower, Toronto, Ontario M5G 1X8 Canada. jrangrej@sickkids.ca

ABSTRACT

Background: Many traits differ by age and sex in humans, but genetic analysis of gene expression has typically not included them in the analysis.

Methods: We used Genetic Analysis Workshop 15 Problem 1 data to determine whether gene expression in lymphoblasts showed differences by age and/or sex using generalized estimating equations (GEE). We performed quantitative trait linkage analysis of these genes including age and sex as covariates to determine whether the linkage results changed when they were included as covariates. Because the families included in the study all contain three generations, we also determined what effect inclusion of generation in the model had on the age effects.

Results: When controlling the false-discovery rate at 1%, using GEE we identified 30 transcripts that showed significant differences in expression by sex, while 1950 transcripts showed differences in expression associated with age. When subjected to linkage analysis, there were 37 linkages that disappeared, while 17 appeared when sex was included as a covariate. All these genes were, as expected, on the sex chromosomes. In contrast, when age was included in the linkage analysis, 462 linkage signals were no longer significant, while 223 became significant. When generation was included in the model with age, all but 6 of the GEE age effects were no longer significant. However, there were minimal changes in the linkage results.

Conclusion: The effect of age on linkage analyses was apparent for the expression of many genes, which appear to be mostly due to differences between the generations.

No MeSH data available.