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Longevity GWAS Using the Drosophila Genetic Reference Panel.

Ivanov DK, Escott-Price V, Ziehm M, Magwire MM, Mackay TF, Partridge L, Thornton JM - J. Gerontol. A Biol. Sci. Med. Sci. (2015)

Bottom Line: We found considerable genetic variation in lifespan in the DGRP, with a broad-sense heritability of 0.413.Genes in the target of rapamycin pathway (TOR; Chrb, slif, mipp2, dredd, RpS9, dm) contributed to the significant enrichment of this pathway among the top-ranked 100 genes (p = 4.79×10(-06)).Gene Ontology analysis suggested that genes involved in carbohydrate metabolism are important for lifespan; including the InterPro term DUF227, which has been previously associated with lifespan determination.

View Article: PubMed Central - PubMed

Affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, Cambridge, UK. divanov@ebi.ac.uk.

No MeSH data available.


Related in: MedlinePlus

Manhattan plot for gene-based GWAS. Each point represents a gene. The height of the gene represents the strength of association with lifespan, expressed as −log10(p value). The red horizontal line represents genome-wide Bonferroni significance threshold (p = 3.53×10−06).
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Figure 3: Manhattan plot for gene-based GWAS. Each point represents a gene. The height of the gene represents the strength of association with lifespan, expressed as −log10(p value). The red horizontal line represents genome-wide Bonferroni significance threshold (p = 3.53×10−06).

Mentions: As noted above, power calculations suggest that single-SNP association analysis is underpowered for SNPs with MAF < 0.3. Gene-based GWAS on the other hand can increase the power to detect the combined effects of multiple variants within a gene (25,42). We therefore assessed the significance of the combined Fisher’s T-statistic for all common SNPs (MAF ≥ 2%; see Materials and Methods for definition of gene positions) in each annotated Drosophila gene. Of the 15,683 genes in the fly genome, 14,146 had at least two SNPs (MAF≥2%). None of the gene-based association tests exceeded the Bonferroni-corrected significance threshold (p = 3.53×10−06, Figure 3 and Supplementary Figure 9).


Longevity GWAS Using the Drosophila Genetic Reference Panel.

Ivanov DK, Escott-Price V, Ziehm M, Magwire MM, Mackay TF, Partridge L, Thornton JM - J. Gerontol. A Biol. Sci. Med. Sci. (2015)

Manhattan plot for gene-based GWAS. Each point represents a gene. The height of the gene represents the strength of association with lifespan, expressed as −log10(p value). The red horizontal line represents genome-wide Bonferroni significance threshold (p = 3.53×10−06).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4631106&req=5

Figure 3: Manhattan plot for gene-based GWAS. Each point represents a gene. The height of the gene represents the strength of association with lifespan, expressed as −log10(p value). The red horizontal line represents genome-wide Bonferroni significance threshold (p = 3.53×10−06).
Mentions: As noted above, power calculations suggest that single-SNP association analysis is underpowered for SNPs with MAF < 0.3. Gene-based GWAS on the other hand can increase the power to detect the combined effects of multiple variants within a gene (25,42). We therefore assessed the significance of the combined Fisher’s T-statistic for all common SNPs (MAF ≥ 2%; see Materials and Methods for definition of gene positions) in each annotated Drosophila gene. Of the 15,683 genes in the fly genome, 14,146 had at least two SNPs (MAF≥2%). None of the gene-based association tests exceeded the Bonferroni-corrected significance threshold (p = 3.53×10−06, Figure 3 and Supplementary Figure 9).

Bottom Line: We found considerable genetic variation in lifespan in the DGRP, with a broad-sense heritability of 0.413.Genes in the target of rapamycin pathway (TOR; Chrb, slif, mipp2, dredd, RpS9, dm) contributed to the significant enrichment of this pathway among the top-ranked 100 genes (p = 4.79×10(-06)).Gene Ontology analysis suggested that genes involved in carbohydrate metabolism are important for lifespan; including the InterPro term DUF227, which has been previously associated with lifespan determination.

View Article: PubMed Central - PubMed

Affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, Cambridge, UK. divanov@ebi.ac.uk.

No MeSH data available.


Related in: MedlinePlus