GWAS of longevity in CHARGE consortium confirms APOE and FOXO3 candidacy.

TitleGWAS of longevity in CHARGE consortium confirms APOE and FOXO3 candidacy.
Publication TypeJournal Article
Year of Publication2015
AuthorsBroer, L, Aron S. Buchman, Deelen, J, Evans, DS, Faul, JD, Lunetta, KL, Sebastiani, P, Smith, JA, Smith, AVernon, Tanaka, T, Yu, L, Arnold, AM, Aspelund, T, Emelia J. Benjamin, De Jager, PL, Eiríksdóttir, G, Garcia, ME, Hofman, A, Kaplan, RC, Kardia, SLR, Kiel, DP, Oostra, BA, Orwoll, ES, Parimi, N, Psaty, BM, Rivadeneira, F, Rotter, JI, Seshadri, S, Singleton, AB, Tiemeier, H, Uitterlinden, AG, Zhao, W, Bandinelli, S, Bennett, DA, Ferrucci, L, Gudnason, V, Harris, TB, Karasik, D, Launer, LJ, Perls, T, Slagboom, EP, Tranah, GJ, Weir, DR, Newman, AB, van Duijn, CM, Murabito, JM
JournalJournals of Gerontology Series A: Biological Sciences and Medical Sciences
Volume70
Issue1
Pagination110-8
Date Published2015 Jan
ISSN Number1758-535X
KeywordsCHARGE, Genetics, Longevity, Mortality, Older Adults
Abstract

BACKGROUND: The genetic contribution to longevity in humans has been estimated to range from 15% to 25%. Only two genes, APOE and FOXO3, have shown association with longevity in multiple independent studies.

METHODS: We conducted a meta-analysis of genome-wide association studies including 6,036 longevity cases, age ≥90 years, and 3,757 controls that died between ages 55 and 80 years. We additionally attempted to replicate earlier identified single nucleotide polymorphism (SNP) associations with longevity.

RESULTS: In our meta-analysis, we found suggestive evidence for the association of SNPs near CADM2 (odds ratio [OR] = 0.81; p value = 9.66 × 10(-7)) and GRIK2 (odds ratio = 1.24; p value = 5.09 × 10(-8)) with longevity. When attempting to replicate findings earlier identified in genome-wide association studies, only the APOE locus consistently replicated. In an additional look-up of the candidate gene FOXO3, we found that an earlier identified variant shows a highly significant association with longevity when including published data with our meta-analysis (odds ratio = 1.17; p value = 1.85×10(-10)).

CONCLUSIONS: We did not identify new genome-wide significant associations with longevity and did not replicate earlier findings except for APOE and FOXO3. Our inability to find new associations with survival to ages ≥90 years because longevity represents multiple complex traits with heterogeneous genetic underpinnings, or alternatively, that longevity may be regulated by rare variants that are not captured by standard genome-wide genotyping and imputation of common variants.

URLhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4296168/
DOI10.1093/gerona/glu166
Alternate JournalJ. Gerontol. A Biol. Sci. Med. Sci.
Citation Key8606
PubMed ID25199915
PubMed Central IDPMC4296168
Grant List1R01AG028321 / AG / NIA NIH HHS / United States
1R01HL092577 / HL / NHLBI NIH HHS / United States
263 MD 821336 / MD / NIMHD NIH HHS / United States
263 MD 9164 / MD / NIMHD NIH HHS / United States
AG023629 / AG / NIA NIH HHS / United States
DK063491 / DK / NIDDK NIH HHS / United States
HHSN268200800007C / / PHS HHS / United States
HHSN268201200036C / / PHS HHS / United States
HL080295 / HL / NHLBI NIH HHS / United States
HL087652 / HL / NHLBI NIH HHS / United States
HL105756 / HL / NHLBI NIH HHS / United States
N01-AG-12100 / AG / NIA NIH HHS / United States
N01-HC-25195 / HC / NHLBI NIH HHS / United States
N01HC55222 / HC / NHLBI NIH HHS / United States
N01HC85079 / HC / NHLBI NIH HHS / United States
N01HC85080 / HC / NHLBI NIH HHS / United States
N01HC85081 / HC / NHLBI NIH HHS / United States
N01HC85082 / HC / NHLBI NIH HHS / United States
N01HC85083 / HC / NHLBI NIH HHS / United States
N01HC85086 / HC / NHLBI NIH HHS / United States
N02-HL-6-4278 / HL / NHLBI NIH HHS / United States
P30 AG010161 / AG / NIA NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
P30AG10161 / AG / NIA NIH HHS / United States
R01 AG005394 / AG / NIA NIH HHS / United States
R01 AG005407 / AG / NIA NIH HHS / United States
R01 AG005407 / AG / NIA NIH HHS / United States
R01 AG011101 / AG / NIA NIH HHS / United States
R01 AG017917 / AG / NIA NIH HHS / United States
R01 AG023629 / AG / NIA NIH HHS / United States
R01 AG027574 / AG / NIA NIH HHS / United States
R01 AG027576 / AG / NIA NIH HHS / United States
R01 AG030146 / AG / NIA NIH HHS / United States
R01 AR/AG 41398 / AG / NIA NIH HHS / United States
R01 AR35582 / AR / NIAMS NIH HHS / United States
R01 AR35583 / AR / NIAMS NIH HHS / United States
R01 AR35584 / AR / NIAMS NIH HHS / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States
R01-AR051124 / AR / NIAMS NIH HHS / United States
R01AG15819 / AG / NIA NIH HHS / United States
R01AG17917 / AG / NIA NIH HHS / United States
R01AG29451 / AG / NIA NIH HHS / United States
R01AG30146 / AG / NIA NIH HHS / United States
RC2 AG036495 / AG / NIA NIH HHS / United States
RC2ARO58973 / RC / CCR NIH HHS / United States
RC4 AG039029 / AG / NIA NIH HHS / United States
RF1 AG015819 / AG / NIA NIH HHS / United States
U01 AG009740 / AG / NIA NIH HHS / United States
U01 AG023749 / AG / NIA NIH HHS / United States
U01 AG023755 / AG / NIA NIH HHS / United States
U01 AG049505 / AG / NIA NIH HHS / United States
U01 AG18197 / AG / NIA NIH HHS / United States
U01 AR066160 / AR / NIAMS NIH HHS / United States
U01 AR45580 / AR / NIAMS NIH HHS / United States
U01 AR45583 / AR / NIAMS NIH HHS / United States
U01 AR45614 / AR / NIAMS NIH HHS / United States
U01 AR45632 / AR / NIAMS NIH HHS / United States
U01 AR45647 / AR / NIAMS NIH HHS / United States
U01 AR45654 / AR / NIAMS NIH HHS / United States
U01-AG023755 / AG / NIA NIH HHS / United States
U01-AG027810 / AG / NIA NIH HHS / United States
U01AG009740 / AG / NIA NIH HHS / United States
U19 AG023122 / AG / NIA NIH HHS / United States
U19-AG023122 / AG / NIA NIH HHS / United States
UL1 RR024140 / RR / NCRR NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
UL1TR000124 / TR / NCATS NIH HHS / United States