TY - JOUR T1 - GWAS of longevity in CHARGE consortium confirms APOE and FOXO3 candidacy. JF - J Gerontol A Biol Sci Med Sci Y1 - 2015 A1 - Broer, Linda A1 - Buchman, Aron S A1 - Deelen, Joris A1 - Evans, Daniel S A1 - Faul, Jessica D A1 - Lunetta, Kathryn L A1 - Sebastiani, Paola A1 - Smith, Jennifer A A1 - Smith, Albert V A1 - Tanaka, Toshiko A1 - Yu, Lei A1 - Arnold, Alice M A1 - Aspelund, Thor A1 - Benjamin, Emelia J A1 - De Jager, Philip L A1 - Eirkisdottir, Gudny A1 - Evans, Denis A A1 - Garcia, Melissa E A1 - Hofman, Albert A1 - Kaplan, Robert C A1 - Kardia, Sharon L R A1 - Kiel, Douglas P A1 - Oostra, Ben A A1 - Orwoll, Eric S A1 - Parimi, Neeta A1 - Psaty, Bruce M A1 - Rivadeneira, Fernando A1 - Rotter, Jerome I A1 - Seshadri, Sudha A1 - Singleton, Andrew A1 - Tiemeier, Henning A1 - Uitterlinden, André G A1 - Zhao, Wei A1 - Bandinelli, Stefania A1 - Bennett, David A A1 - Ferrucci, Luigi A1 - Gudnason, Vilmundur A1 - Harris, Tamara B A1 - Karasik, David A1 - Launer, Lenore J A1 - Perls, Thomas T A1 - Slagboom, P Eline A1 - Tranah, Gregory J A1 - Weir, David R A1 - Newman, Anne B A1 - van Duijn, Cornelia M A1 - Murabito, Joanne M KW - Aged KW - Aged, 80 and over KW - Apolipoproteins E KW - Cell Adhesion Molecules KW - Cohort Studies KW - Female KW - Forkhead Box Protein O3 KW - Forkhead Transcription Factors KW - Genome-Wide Association Study KW - Humans KW - Longevity KW - Male KW - Middle Aged KW - Polymorphism, Single Nucleotide KW - Receptors, Kainic Acid AB -

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.

VL - 70 IS - 1 U1 - http://www.ncbi.nlm.nih.gov/pubmed/25199915?dopt=Abstract ER -