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

Deelen J; Evans DS; Arking DE; Tesi N; Nygaard M; Liu XM; Wojczynski MK; Biggs ML; van Der Spek A; Atzmon G; Ware EB; Sarnowski C; Smith AV; Seppala I; Cordell HJ; Dose J; Amin N; Arnold AM; Ayers KL; Barzilai N; Becker EJ; Beekman M; Blanche 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; Gudnaso V; Harris TB; Huisman M; Hurme MA; Jagger C; Jansen I; Jylha M; Kahonen M; Karasik D; Kardia SLR; Kingston A; Kirkwood TBL; Launer LJ; Lehtimaki T; Lieb WG; Lyytikainen LP; Martin-Ruiz C; Min JX; Nebe A; Newman AB; Nie C; Nohr EA; Orwoll ES; Perls TT; Province MA; Psat BM; Raitakari OT; Reinders MJT; Robine JM; Rotter JI; Sebastiani P; Smith J; Sorensen 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 WL; Holstege H; Kiel DP; Lunetta KL; Slagboom PE; Murabito JM
A meta-analysis of genome-wide association studies identifies multiple longevity genes

Deelen J
Evans DS
Arking DE
Tesi N
Nygaard M
Liu XM
Wojczynski MK
Biggs ML
van Der Spek A
Atzmon G
Ware EB
Sarnowski C
Smith AV
Seppala I
Cordell HJ
Dose J
Amin N
Arnold AM
Ayers KL
Barzilai N
Becker EJ
Beekman M
Blanche 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
Gudnaso V
Harris TB
Huisman M
Hurme MA
Jagger C
Jansen I
Jylha M
Kahonen M
Karasik D
Kardia SLR
Kingston A
Kirkwood TBL
Launer LJ
Lehtimaki T
Lieb WG
Lyytikainen LP
Martin-Ruiz C
Min JX
Nebe A
Newman AB
Nie C
Nohr EA
Orwoll ES
Perls TT
Province MA
Psat BM
Raitakari OT
Reinders MJT
Robine JM
Rotter JI
Sebastiani P
Smith J
Sorensen 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 WL
Holstege H
Kiel DP
Lunetta KL
Slagboom PE
Murabito JM
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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