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Longevity GWAS using the Drosophila Genetic Reference Panel

Ivanov, Dobril K., Escott-Price, Valentina, Ziehm, Matthias, Magwire, Michael M., Mackay, Trudy F. C., Partridge, Linda and Thornton, Janet M. 2015. Longevity GWAS using the Drosophila Genetic Reference Panel. The Journals of Gerontology. Series A: Biological Sciences and Medical Sciences , pii: glv047. 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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Medicine
Subjects: R Medicine > R Medicine (General)
Publisher: Oxford University Press
ISSN: 1079-5006
Last Modified: 04 Jun 2017 08:37
URI: http://orca.cf.ac.uk/id/eprint/81546

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