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Timmers, P.R.* ; Mounier, N.* ; Lall, K.* ; Fischer, K.* ; Ning, Z.* ; Feng, X.* ; Bretherick, A.D.* ; Clark, D.W.* ; eQTLGen Consortium (Agbessi, M.* ; Ahsan, H.* ; Alves, I.* ; Andiappan, A.* ; Awadalla, P.* ; Battle, A.* ; Bonder, M.J.* ; Boomsma, D.* ; Christiansen, M.* ; Claringbould, A.* ; Deelen, P.* ; van Dongen, J.* ; Esko, T.* ; Favé, M.* ; Franke, L.* ; Frayling, T.* ; Gharib, S.A.* ; Gibson, G.* ; Hemani, G.* ; Jansen, R.* ; Kalnapenkis, A.* ; Kasela, S.* ; Kettunen, J.* ; Kim, Y.* ; Kirsten, H.* ; Kovacs, P.* ; Krohn, K.* ; Kronberg-Guzman, J.* ; Kukushkina, V.* ; Kutalik, Z.* ; Kähönen, M.* ; Lee, B.* ; Lehtimäki, T.* ; Loeffler, M.* ; Marigorta, U.* ; Metspalu, A.* ; van Meurs, J.* ; Milani, L.* ; Müller-Nurasyid, M. ; Nauck, M.* ; Nivard, M.* ; Penninx, B.* ; Perola, M.* ; Pervjakova, N.* ; Pierce, B.* ; Powell, J.* ; Prokisch, H. ; Psaty, B.M.* ; Raitakari, O.* ; Ring, S.* ; Ripatti, S.* ; Rotzschke, O.* ; Ruëger, S.* ; Saha, A.* ; Scholz, M.* ; Schramm, K. ; Seppälä, I.* ; Stumvoll, M.* ; Sullivan, P.* ; Teumer, A.* ; Thiery, J.* ; Tong, L.* ; Tönjes, A.* ; Verlouw, J.* ; Visscher, P.M.* ; Võsa, U.* ; Völker, U.* ; Yaghootkar, H.* ; Yang, J.* ; Zeng, B.* ; Zhang, F.*) ; Shen, X.* ; Esko, T.* ; Kutalik, Z.* ; Wilson, J.F.* ; Joshi, P.K.*

Genomics of 1 million parent lifespans implicates novel pathways and common diseases and distinguishes survival chances.

eLife 8:e39856 (2019)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
We use a genome-wide association of 1 million parental lifespans of genotyped subjects and data on mortality risk factors to validate previously unreplicated findings near CDKN2B-AS1, ATXN2/BRAP, FURIN/FES, ZW10, PSORS1C3, and 13q21.31, and identify and replicate novel findings near ABO, ZC3HC1, and IGF2R. We also validate previous findings near 5q33.3/EBF1 and FOXO3, whilst finding contradictory evidence at other loci. Gene set and cell-specific analyses show that expression in foetal brain cells and adult dorsolateral prefrontal cortex is enriched for lifespan variation, as are gene pathways involving lipid proteins and homeostasis, vesicle-mediated transport, and synaptic function. Individual genetic variants that increase dementia, cardiovascular disease, and lung cancer - but not other cancers - explain the most variance. Resulting polygenic scores show a mean lifespan difference of around five years of life across the deciles. Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).
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Publication type Article: Journal article
Document type Scientific Article
Keywords Complex Trait ; Genetics ; Genomics ; Human ; Lifespan ; Longevity
Language english
Publication Year 2019
HGF-reported in Year 2019
ISSN (print) / ISBN 2050-084X
e-ISSN 2050-084X
Journal eLife
Quellenangaben Volume: 8, Issue: , Pages: , Article Number: e39856 Supplement: ,
Publisher eLife Sciences Publications
Reviewing status Peer reviewed
Institute(s) Institute of Genetic Epidemiology (IGE)
Institute of Human Genetics (IHG)
POF-Topic(s) 30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Research field(s) Genetics and Epidemiology
PSP Element(s) G-504100-001
G-500700-001
DOI 10.7554/eLife.39856
Scopus ID 85060022694
PubMed ID 30642433
Erfassungsdatum 2019-03-11
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