Ivanov, DK;
Escott-Price, V;
Ziehm, M;
Magwire, MM;
Mackay, TF;
Partridge, L;
Thornton, JM;
(2015)
Longevity GWAS Using the Drosophila Genetic Reference Panel.
Journals of Gerontology: Series A
, 70
(12)
pp. 1470-1478.
10.1093/gerona/glv047.
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Abstract
We used 197 Drosophila melanogaster Genetic Reference Panel (DGRP) lines to perform a genome-wide association analysis for virgin female lifespan, using ~2M common single nucleotide polymorphisms (SNPs). We found considerable genetic variation in lifespan in the DGRP, with a broad-sense heritability of 0.413. There was little power to detect signals at a genome-wide level in single-SNP and gene-based analyses. Polygenic score analysis revealed that a small proportion of the variation in lifespan (~4.7%) was explicable in terms of additive effects of common SNPs (≥2% minor allele frequency). However, several of the top associated genes are involved in the processes previously shown to impact ageing (eg, carbohydrate-related metabolism, regulation of cell death, proteolysis). Other top-ranked genes are of unknown function and provide promising candidates for experimental examination. 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. This analysis suggests that our understanding of the genetic basis of natural variation in lifespan from induced mutations is incomplete.
| Type: | Article |
|---|---|
| Title: | Longevity GWAS Using the Drosophila Genetic Reference Panel |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1093/gerona/glv047 |
| Publisher version: | http://dx.doi.org/10.1093/gerona/glv047 |
| Language: | English |
| Additional information: | © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | Ageing, Gene ontology, Gene-based analysis, Insulin signaling pathway., Polygenic score analysis, Target of rapamycin |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1471717 |
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