A meta-analysis of genome-wide association studies identifies multiple longevity genes

Deelen, Joris; Evans, Daniel S.; Arking, Dan E.; Tesi, Niccolò; Nygaard, Marianne; Liu, Xiaomin; Wojczynski, Mary K.; Biggs, Mary L.; van der Spek, Ashley; Atzmon, Gil; Ware, Erin B.; Sarnowski, Chloé; Smith, Albert Vernon; Seppälä, Ilkka; Cordell, Heather J.; Dose, Janina; Amin, Najaf; Arnold, Alice M.; Ayers, Kristin L.; Barzilai, Nir; Becker, Elizabeth J.; Beekman, Marian; Blanché, Hélène; Christensen, Kaare; Christiansen, Lene; Collerton, Joanna C.; Cubaynes, Sarah; Cummings, Steven R.; Davies, Karen; Debrabant, Birgit; Deleuze, Jean-François; Duncan, Rachel; Faul, Jessica D.; Franceschi, Claudio; Galan, Pilar; Gudnason, Vilmundur; Harris, Tamara B.; Huisman, Martijn; Hurme, Mikko A.; Jagger, Carol; Jansen, Iris; Jylhä, Marja; Kähönen, Mika; Karasik, David; Kardia, Sharon L. R.; Kingston, Andrew; Kirkwood, Thomas B. L.; Launer, Lenore J.; Lehtimäki, Terho; Lieb, Wolfgang; Lyytikäinen, Leo-Pekka; Martin-Ruiz, Carmen; Min, Junxia; Nebel, Almut; Newman, Anne B.; Nie, Chao; Nohr, Ellen A.; Orwoll, Eric S.; Perls, Thomas T.; Province, Michael A.; Psaty, Bruce M.; Raitakari, Olli T.; Reinders, Marcel J. T.; Robine, Jean-Marie; Rotter, Jerome I.; Sebastiani, Paola; Smith, Jennifer; Sørensen, Thorkild I. A.; Taylor, Kent D.; Uitterlinden, André G.; van der Flier, Wiesje; van der Lee, Sven J.; van Duijn, Cornelia M.; van Heemst, Diana; Vaupel, James W.; Weir, David; Ye, Kenny; Zeng, Yi; Zheng, Wanlin; Holstege, Henne; Kiel, Douglas P.; Lunetta, Kathryn L.; Slagboom, P. Eline; Murabito, Joanne M.

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dc.contributor	Háskóli Íslands
dc.contributor	University of Iceland
dc.contributor.author	Deelen, Joris
dc.contributor.author	Evans, Daniel S.
dc.contributor.author	Arking, Dan E.
dc.contributor.author	Tesi, Niccolò
dc.contributor.author	Nygaard, Marianne
dc.contributor.author	Liu, Xiaomin
dc.contributor.author	Wojczynski, Mary K.
dc.contributor.author	Biggs, Mary L.
dc.contributor.author	van der Spek, Ashley
dc.contributor.author	Atzmon, Gil
dc.contributor.author	Ware, Erin B.
dc.contributor.author	Sarnowski, Chloé
dc.contributor.author	orcid.org/0000-0003-1942-5845 Smith, Albert Vernon
dc.contributor.author	Seppälä, Ilkka
dc.contributor.author	Cordell, Heather J.
dc.contributor.author	Dose, Janina
dc.contributor.author	Amin, Najaf
dc.contributor.author	Arnold, Alice M.
dc.contributor.author	Ayers, Kristin L.
dc.contributor.author	Barzilai, Nir
dc.contributor.author	Becker, Elizabeth J.
dc.contributor.author	Beekman, Marian
dc.contributor.author	Blanché, Hélène
dc.contributor.author	Christensen, Kaare
dc.contributor.author	Christiansen, Lene
dc.contributor.author	Collerton, Joanna C.
dc.contributor.author	Cubaynes, Sarah
dc.contributor.author	Cummings, Steven R.
dc.contributor.author	Davies, Karen
dc.contributor.author	Debrabant, Birgit
dc.contributor.author	Deleuze, Jean-François
dc.contributor.author	Duncan, Rachel
dc.contributor.author	Faul, Jessica D.
dc.contributor.author	Franceschi, Claudio
dc.contributor.author	Galan, Pilar
dc.contributor.author	orcid.org/0000-0001-5696-0084 Gudnason, Vilmundur
dc.contributor.author	Harris, Tamara B.
dc.contributor.author	Huisman, Martijn
dc.contributor.author	Hurme, Mikko A.
dc.contributor.author	Jagger, Carol
dc.contributor.author	Jansen, Iris
dc.contributor.author	Jylhä, Marja
dc.contributor.author	Kähönen, Mika
dc.contributor.author	Karasik, David
dc.contributor.author	Kardia, Sharon L. R.
dc.contributor.author	Kingston, Andrew
dc.contributor.author	Kirkwood, Thomas B. L.
dc.contributor.author	Launer, Lenore J.
dc.contributor.author	Lehtimäki, Terho
dc.contributor.author	Lieb, Wolfgang
dc.contributor.author	Lyytikäinen, Leo-Pekka
dc.contributor.author	Martin-Ruiz, Carmen
dc.contributor.author	Min, Junxia
dc.contributor.author	Nebel, Almut
dc.contributor.author	Newman, Anne B.
dc.contributor.author	Nie, Chao
dc.contributor.author	Nohr, Ellen A.
dc.contributor.author	Orwoll, Eric S.
dc.contributor.author	Perls, Thomas T.
dc.contributor.author	Province, Michael A.
dc.contributor.author	Psaty, Bruce M.
dc.contributor.author	Raitakari, Olli T.
dc.contributor.author	Reinders, Marcel J. T.
dc.contributor.author	Robine, Jean-Marie
dc.contributor.author	Rotter, Jerome I.
dc.contributor.author	Sebastiani, Paola
dc.contributor.author	Smith, Jennifer
dc.contributor.author	Sørensen, Thorkild I. A.
dc.contributor.author	Taylor, Kent D.
dc.contributor.author	Uitterlinden, André G.
dc.contributor.author	van der Flier, Wiesje
dc.contributor.author	van der Lee, Sven J.
dc.contributor.author	van Duijn, Cornelia M.
dc.contributor.author	van Heemst, Diana
dc.contributor.author	Vaupel, James W.
dc.contributor.author	Weir, David
dc.contributor.author	Ye, Kenny
dc.contributor.author	Zeng, Yi
dc.contributor.author	Zheng, Wanlin
dc.contributor.author	Holstege, Henne
dc.contributor.author	Kiel, Douglas P.
dc.contributor.author	Lunetta, Kathryn L.
dc.contributor.author	Slagboom, P. Eline
dc.contributor.author	Murabito, Joanne M.
dc.date.accessioned	2020-03-02T13:43:26Z
dc.date.available	2020-03-02T13:43:26Z
dc.date.issued	2019-08-14
dc.identifier.citation	Deelen, J., Evans, D.S., Arking, D.E. et al. A meta-analysis of genome-wide association studies identifies multiple longevity genes. Nat Commun 10, 3669 (2019). https://doi.org/10.1038/s41467-019-11558-2
dc.identifier.issn	2041-1723
dc.identifier.uri	https://hdl.handle.net/20.500.11815/1567
dc.description	Publisher's version (útgefin grein).
dc.description.abstract	Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a rigorous longevity phenotype definition including 11,262/3484 cases surviving at or beyond the age corresponding to the 90th/99th survival percentile, respectively, and 25,483 controls whose age at death or at last contact was at or below the age corresponding to the 60th survival percentile. Consistent with previous reports, rs429358 (apolipoprotein E (ApoE) ε4) is associated with lower odds of surviving to the 90th and 99th percentile age, while rs7412 (ApoE ε2) shows the opposite. Moreover, rs7676745, located near GPR78, associates with lower odds of surviving to the 90th percentile age. Gene-level association analysis reveals a role for tissue-specific expression of multiple genes in longevity. Finally, genetic correlation of the longevity GWA results with that of several disease-related phenotypes points to a shared genetic architecture between health and longevity.
dc.description.sponsorship	Alexander von Humboldt-Stiftung
dc.format.extent	3669
dc.language.iso	en
dc.publisher	Springer Science and Business Media LLC
dc.relation.ispartofseries	Nature Communications;10(1)
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	Ageing
dc.subject	Diseases
dc.subject	Genome-wide association studies
dc.subject	Risk factors
dc.subject	Öldrun
dc.subject	Sjúkdómar
dc.subject	Áhættuþættir
dc.subject	Erfðarannsóknir
dc.title	A meta-analysis of genome-wide association studies identifies multiple longevity genes
dc.type	info:eu-repo/semantics/article
dcterms.license	Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
dc.description.version	Peer Reviewed
dc.identifier.journal	Nature Communications
dc.identifier.doi	10.1038/s41467-019-11558-2
dc.contributor.department	Læknadeild (HÍ)
dc.contributor.department	Faculty of Medicine (UI)
dc.contributor.school	Heilbrigðisvísindasvið (HÍ)
dc.contributor.school	School of Health Sciences (UI)