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

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Version: Final published version
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Serval ID
serval:BIB_771D2C9E3799
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Genomics of 1 million parent lifespans implicates novel pathways and common diseases and distinguishes survival chances.
Journal
eLife
Author(s)
Timmers P.R., Mounier N., Lall K., Fischer K., Ning Z., Feng X., Bretherick A.D., Clark D.W., 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., 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.
Working group(s)
eQTLGen Consortium
ISSN
2050-084X (Electronic)
ISSN-L
2050-084X
Publication state
Published
Issued date
15/01/2019
Peer-reviewed
Oui
Volume
8
Pages
e39856
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
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.
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).
Keywords
Age Factors, Aged, Bayes Theorem, DNA Methylation/genetics, Disease/genetics, Female, Genetic Loci, Genome-Wide Association Study, Genomics, Humans, Longevity/genetics, Male, Middle Aged, Multifactorial Inheritance/genetics, Parents, Polymorphism, Single Nucleotide/genetics, Risk Factors, Sex Characteristics, Signal Transduction/genetics, Survival Analysis, complex trait, genetics, genomics, human, lifespan, longevity
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2019 15:57
Last modification date
27/04/2020 5:20
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