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

van Duijn CM; van Der Spek A; Arnold AM; Cummings SR; Duncan R; Seppala I; Zeng Y; Uitterlinden AG; Jylha M; Jagger C; Smith J; Faul JD; Sorensen TIA; Orwoll ES; Perls TT; Rotter JI; Barzilai N; Sarnowski C; Psat BM; Debrabant B; Huisman M; Christensen K; Nohr EA; Robine JM; Blanche H; Tesi N; Liu XM; Province MA; Gudnaso V; Amin N; Ye K; Holstege H; Becker EJ; Slagboom PE; Weir D; Kahonen M; Deelen J; Lieb WG; van Der Flier W; Cordell HJ; Lehtimaki T; Smith AV; Wojczynski MK; Newman AB; Murabito JM; Kardia SLR; Atzmon G; Kirkwood TBL; Ayers KL; Nygaard M; Jansen I; van Der Lee SJ; Karasik D; Galan P; Cubaynes S; Christiansen L; Taylor KD; Deleuze JF; Vaupel JW; Dose J; Martin-Ruiz C; Launer LJ; Biggs ML; Sebastiani P; Franceschi C; Arking DE; Lyytikainen LP; Evans DS; Ware EB; Lunetta KL; Kiel DP; Min JX; Beekman M; van Heemst D; Collerton JC; Nebe A; Zheng WL; Nie C; Davies K; Raitakari OT; Kingston A; Hurme MA; Harris TB; Reinders MJT
A meta-analysis of genome-wide association studies identifies multiple longevity genes

van Duijn CM
van Der Spek A
Arnold AM
Cummings SR
Duncan R
Seppala I
Zeng Y
Uitterlinden AG
Jylha M
Jagger C
Smith J
Faul JD
Sorensen TIA
Orwoll ES
Perls TT
Rotter JI
Barzilai N
Sarnowski C
Psat BM
Debrabant B
Huisman M
Christensen K
Nohr EA
Robine JM
Blanche H
Tesi N
Liu XM
Province MA
Gudnaso V
Amin N
Ye K
Holstege H
Becker EJ
Slagboom PE
Weir D
Kahonen M
Deelen J
Lieb WG
van Der Flier W
Cordell HJ
Lehtimaki T
Smith AV
Wojczynski MK
Newman AB
Murabito JM
Kardia SLR
Atzmon G
Kirkwood TBL
Ayers KL
Nygaard M
Jansen I
van Der Lee SJ
Karasik D
Galan P
Cubaynes S
Christiansen L
Taylor KD
Deleuze JF
Vaupel JW
Dose J
Martin-Ruiz C
Launer LJ
Biggs ML
Sebastiani P
Franceschi C
Arking DE
Lyytikainen LP
Evans DS
Ware EB
Lunetta KL
Kiel DP
Min JX
Beekman M
van Heemst D
Collerton JC
Nebe A
Zheng WL
Nie C
Davies K
Raitakari OT
Kingston A
Hurme MA
Harris TB
Reinders MJT
Katso/Avaa
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NATURE PUBLISHING GROUP
doi:10.1038/s41467-019-11558-2
URI
https://www.nature.com/articles/s41467-019-11558-2
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Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2021042822804
Tiivistelmä
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) epsilon 4) is associated with lower odds of surviving to the 90th and 99th percentile age, while rs7412 (ApoE epsilon 2) 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.
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