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

Joris Deelen*, Daniel S. Evans, Dan E. Arking, Niccolò Tesi, Marianne Nygaard, Xiaomin Liu, Mary K. Wojczynski, Mary L. Biggs, Ashley van der Spek, Gil Atzmon, Erin B. Ware, Chloé Sarnowski, Albert V. Smith, Ilkka Seppälä, Heather J. Cordell, Janina Dose, Najaf Amin, Alice M. Arnold, Kristin L. Ayers, Nir Barzilai & 64 andre Elizabeth J. Becker, Marian Beekman, Hélène Blanché, Kaare Christensen, Lene Christiansen, Joanna C. Collerton, Sarah Cubaynes, Steven R. Cummings, Karen Davies, Birgit Debrabant, Jean François Deleuze, Rachel Duncan, Jessica D. Faul, Claudio Franceschi, Pilar Galan, Vilmundur Gudnason, Tamara B. Harris, Martijn Huisman, Mikko A. Hurme, Carol Jagger, Iris Jansen, Marja Jylhä, Mika Kähönen, David Karasik, Sharon L.R. Kardia, Andrew Kingston, Thomas B.L. Kirkwood, Lenore J. Launer, Terho Lehtimäki, Wolfgang Lieb, Leo Pekka Lyytikäinen, Carmen Martin-Ruiz, Junxia Min, Almut Nebel, Anne B. Newman, Chao Nie, Ellen A. Nohr, Eric S. Orwoll, Thomas T. Perls, Michael A. Province, Bruce M. Psaty, Olli T. Raitakari, Marcel J.T. Reinders, Jean Marie Robine, Jerome I. Rotter, Paola Sebastiani, Jennifer Smith, Thorkild I.A. Sørensen, Kent D. Taylor, André G. Uitterlinden, Wiesje van der Flier, Sven J. van der Lee, Cornelia M. van Duijn, Diana van Heemst, James W. Vaupel, David Weir, Kenny Ye, Yi Zeng, Wanlin Zheng, Henne Holstege, Douglas P. Kiel, Kathryn L. Lunetta, P. Eline Slagboom, Joanne M. Murabito

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Resumé

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.

OriginalsprogEngelsk
Artikelnummer3669
TidsskriftNature Communications
Vol/bind10
Udgave nummer1
Antal sider14
ISSN2041-1723
DOI
StatusUdgivet - 1. dec. 2019

Fingeraftryk

genome
Genome-Wide Association Study
genes
Meta-Analysis
Genes
phenotype
Apolipoprotein E2
Apolipoprotein E4
death
health
Health
Tissue

Citer dette

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 V. ; 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. / A meta-analysis of genome-wide association studies identifies multiple longevity genes. I: Nature Communications. 2019 ; Bind 10, Nr. 1.
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title = "A meta-analysis of genome-wide association studies identifies multiple longevity genes",
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.",
author = "Joris Deelen and Evans, {Daniel S.} and Arking, {Dan E.} and Niccol{\`o} Tesi and Marianne Nygaard and Xiaomin Liu and Wojczynski, {Mary K.} and Biggs, {Mary L.} and {van der Spek}, Ashley and Gil Atzmon and Ware, {Erin B.} and Chlo{\'e} Sarnowski and Smith, {Albert V.} and Ilkka Sepp{\"a}l{\"a} and Cordell, {Heather J.} and Janina Dose and Najaf Amin and Arnold, {Alice M.} and Ayers, {Kristin L.} and Nir Barzilai and Becker, {Elizabeth J.} and Marian Beekman and H{\'e}l{\`e}ne Blanch{\'e} and Kaare Christensen and Lene Christiansen and Collerton, {Joanna C.} and Sarah Cubaynes and Cummings, {Steven R.} and Karen Davies and Birgit Debrabant and Deleuze, {Jean Fran{\cc}ois} and Rachel Duncan and Faul, {Jessica D.} and Claudio Franceschi and Pilar Galan and Vilmundur Gudnason and Harris, {Tamara B.} and Martijn Huisman and Hurme, {Mikko A.} and Carol Jagger and Iris Jansen and Marja Jylh{\"a} and Mika K{\"a}h{\"o}nen and David Karasik and Kardia, {Sharon L.R.} and Andrew Kingston and Kirkwood, {Thomas B.L.} and Launer, {Lenore J.} and Terho Lehtim{\"a}ki and Wolfgang Lieb and Lyytik{\"a}inen, {Leo Pekka} and Carmen Martin-Ruiz and Junxia Min and Almut Nebel and Newman, {Anne B.} and Chao Nie and Nohr, {Ellen A.} and Orwoll, {Eric S.} and Perls, {Thomas T.} and Province, {Michael A.} and Psaty, {Bruce M.} and Raitakari, {Olli T.} and Reinders, {Marcel J.T.} and Robine, {Jean Marie} and Rotter, {Jerome I.} and Paola Sebastiani and Jennifer Smith and S{\o}rensen, {Thorkild I.A.} and Taylor, {Kent D.} and Uitterlinden, {Andr{\'e} G.} and {van der Flier}, Wiesje and {van der Lee}, {Sven J.} and {van Duijn}, {Cornelia M.} and {van Heemst}, Diana and Vaupel, {James W.} and David Weir and Kenny Ye and Yi Zeng and Wanlin Zheng and Henne Holstege and Kiel, {Douglas P.} and Lunetta, {Kathryn L.} and Slagboom, {P. Eline} and Murabito, {Joanne M.}",
year = "2019",
month = "12",
day = "1",
doi = "10.1038/s41467-019-11558-2",
language = "English",
volume = "10",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",

}

Deelen, J, Evans, DS, Arking, DE, Tesi, N, Nygaard, M, Liu, X, Wojczynski, MK, Biggs, ML, van der Spek, A, Atzmon, G, Ware, EB, Sarnowski, C, Smith, AV, Seppälä, I, Cordell, HJ, Dose, J, Amin, N, Arnold, AM, Ayers, KL, Barzilai, N, Becker, EJ, Beekman, M, Blanché, H, Christensen, K, Christiansen, L, Collerton, JC, Cubaynes, S, Cummings, SR, Davies, K, Debrabant, B, Deleuze, JF, Duncan, R, Faul, JD, Franceschi, C, Galan, P, Gudnason, V, Harris, TB, Huisman, M, Hurme, MA, Jagger, C, Jansen, I, Jylhä, M, Kähönen, M, Karasik, D, Kardia, SLR, Kingston, A, Kirkwood, TBL, Launer, LJ, Lehtimäki, T, Lieb, W, Lyytikäinen, LP, Martin-Ruiz, C, Min, J, Nebel, A, Newman, AB, Nie, C, Nohr, EA, Orwoll, ES, Perls, TT, Province, MA, Psaty, BM, Raitakari, OT, Reinders, MJT, Robine, JM, Rotter, JI, Sebastiani, P, Smith, J, Sørensen, TIA, Taylor, KD, Uitterlinden, AG, van der Flier, W, van der Lee, SJ, van Duijn, CM, van Heemst, D, Vaupel, JW, Weir, D, Ye, K, Zeng, Y, Zheng, W, Holstege, H, Kiel, DP, Lunetta, KL, Slagboom, PE & Murabito, JM 2019, 'A meta-analysis of genome-wide association studies identifies multiple longevity genes', Nature Communications, bind 10, nr. 1, 3669. https://doi.org/10.1038/s41467-019-11558-2

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 V.; 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.

I: Nature Communications, Bind 10, Nr. 1, 3669, 01.12.2019.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - A meta-analysis of genome-wide association studies identifies multiple longevity genes

AU - Deelen, Joris

AU - Evans, Daniel S.

AU - Arking, Dan E.

AU - Tesi, Niccolò

AU - Nygaard, Marianne

AU - Liu, Xiaomin

AU - Wojczynski, Mary K.

AU - Biggs, Mary L.

AU - van der Spek, Ashley

AU - Atzmon, Gil

AU - Ware, Erin B.

AU - Sarnowski, Chloé

AU - Smith, Albert V.

AU - Seppälä, Ilkka

AU - Cordell, Heather J.

AU - Dose, Janina

AU - Amin, Najaf

AU - Arnold, Alice M.

AU - Ayers, Kristin L.

AU - Barzilai, Nir

AU - Becker, Elizabeth J.

AU - Beekman, Marian

AU - Blanché, Hélène

AU - Christensen, Kaare

AU - Christiansen, Lene

AU - Collerton, Joanna C.

AU - Cubaynes, Sarah

AU - Cummings, Steven R.

AU - Davies, Karen

AU - Debrabant, Birgit

AU - Deleuze, Jean François

AU - Duncan, Rachel

AU - Faul, Jessica D.

AU - Franceschi, Claudio

AU - Galan, Pilar

AU - Gudnason, Vilmundur

AU - Harris, Tamara B.

AU - Huisman, Martijn

AU - Hurme, Mikko A.

AU - Jagger, Carol

AU - Jansen, Iris

AU - Jylhä, Marja

AU - Kähönen, Mika

AU - Karasik, David

AU - Kardia, Sharon L.R.

AU - Kingston, Andrew

AU - Kirkwood, Thomas B.L.

AU - Launer, Lenore J.

AU - Lehtimäki, Terho

AU - Lieb, Wolfgang

AU - Lyytikäinen, Leo Pekka

AU - Martin-Ruiz, Carmen

AU - Min, Junxia

AU - Nebel, Almut

AU - Newman, Anne B.

AU - Nie, Chao

AU - Nohr, Ellen A.

AU - Orwoll, Eric S.

AU - Perls, Thomas T.

AU - Province, Michael A.

AU - Psaty, Bruce M.

AU - Raitakari, Olli T.

AU - Reinders, Marcel J.T.

AU - Robine, Jean Marie

AU - Rotter, Jerome I.

AU - Sebastiani, Paola

AU - Smith, Jennifer

AU - Sørensen, Thorkild I.A.

AU - Taylor, Kent D.

AU - Uitterlinden, André G.

AU - van der Flier, Wiesje

AU - van der Lee, Sven J.

AU - van Duijn, Cornelia M.

AU - van Heemst, Diana

AU - Vaupel, James W.

AU - Weir, David

AU - Ye, Kenny

AU - Zeng, Yi

AU - Zheng, Wanlin

AU - Holstege, Henne

AU - Kiel, Douglas P.

AU - Lunetta, Kathryn L.

AU - Slagboom, P. Eline

AU - Murabito, Joanne M.

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-019-11558-2

DO - 10.1038/s41467-019-11558-2

M3 - Journal article

VL - 10

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 3669

ER -