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Analysis of lifespan across diversity outbred mouse studies identifies multiple longevity-associated loci

Title: Analysis of lifespan across diversity outbred mouse studies identifies multiple longevity-associated loci
Authors: Mullis, Martin N; Wright, Kevin M; Raj, Anil; Gatti, Daniel M; Reifsnyder, Peter C; Flurkey, Kevin; Archer, Jonathan R; Robinson, Laura; Di Francesco, Andrea; Svenson, Karen L; Korstanje, Ron; Harrison, David E; Ruby, J Graham; Churchill, Gary A
Contributors: Flint, J; National Institutes of Health; Ellison Medical Foundation Senior Scholar Award; Calico Life Sciences LLC
Source: GENETICS ; volume 230, issue 4 ; ISSN 1943-2631
Publisher Information: Oxford University Press (OUP)
Publication Year: 2025
Description: Lifespan is an integrative phenotype whose genetic architecture is likely to highlight multiple processes with high impact on health and aging. Here, we conducted a genetic mega-analysis of longevity in Diversity Outbred (DO) mice that included 2,444 animals from 3 independently conducted lifespan studies. We identified 8 loci that contributed significantly to lifespan independently of diet and drug treatment in at least one study. One of these loci also influenced lifespan in a sex-dependent manner, and we detected an additional locus with a diet-specific effect on lifespan. Collectively, these loci explained over half of the estimated heritable variation in lifespan across these studies and provided insight into the genetic architecture of lifespan in DO mice.
Document Type: article in journal/newspaper
Language: English
DOI: 10.1093/genetics/iyaf081
DOI: 10.1093/genetics/iyaf081/63067906/iyaf081.pdf
Availability: https://doi.org/10.1093/genetics/iyaf081; https://academic.oup.com/genetics/advance-article-pdf/doi/10.1093/genetics/iyaf081/63067906/iyaf081.pdf; https://academic.oup.com/genetics/article-pdf/230/4/iyaf081/63067906/iyaf081.pdf
Rights: https://creativecommons.org/licenses/by/4.0/
Accession Number: edsbas.FDF2D9AB
Database: BASE