Appendix A. Supplementary data
Supplementary data associated with this article can be found in the online version at doi:10.1016/j.mad.2011.06.008.

References
Anselmi, C.V., Malovini, A., Roncarati, R., Novelli, V., Villa, F., Condorelli, G., Southern Italian Centenarian Study. Rejuvenation Res. 12(3), 201-206 (2009).
Barrett, J.C., Hansoul, S., Nicolae, D.L., Cho, J.H., Duerr, R.H., Rioux, J.D., Brant, Silverberg, M.S., Taylor, K.D., Barmada, M.M., Bitton, A., Dassopoulos, T., Lathrop, M., Belaiche, J., Dewit, O., Gut, I., Heath, S., Laukens, D., Mni Rutgeerts, P., Van Gossum, A., Zelenika, D., Franchimont, D., Hugot, J.P., Vos M., Vermeire S., Louis E.. Cardon L.R.. Anderson C.A.. Drummond H.. Nimmo E.. Ahmad T.. Prescott N.J.. Onnie C.M.. Fisher S.A.. Marchini J.. Ghori J. ..Bumpstead S..Gwilliam R..Tremelling M..Deloukas P..Mansfield J..Satsangi J..Mathew C.G.. Parkes M.. Georges M.. Daly M.J.. Genome-wide association study of ulcerative colitis identifies three new susceptibility loci, including the HNF4A region. Nat. Genet. 41(12), 1330-1334 (2009).
Blanche, H., Cabanne, L., Sahbatou, M., Thomas, G.. A study of centenarians: are ACE and APOE associated with longevity? CR Acad. Sci. 318(1), 23-29 (1995).
Browning, B.L., Browning, S.R.. A unified approach to genotype and haplotype-phase inference for large data sets of trios and unrelated individuals. Am. J. Hum. Genet. 84(2), 210-223 (2009).
Chen, Y., Xiong, D.H., Guo, Y.F., Pan, F., Zhou, Q., Zhang, F., Deng, H.W.. Pathway-based genome-wide association analysis identified the importance of the Ephrin-Ep pathway for femoral neck bone geometry. Bone 48(4), 964-971 (2011).
de CraA.J., Rivadeneira, F., Geus, E.J., Perola, M., van der Ouderaa, F.J., Gunn, D.A., Boomsma, D.I., Linden, A.G., Christensen, K., van Duijn, C.M., Heijmans, B.T., Termaat, J.J., Westendorp, R.G., Slagboom, P.E. Genome-wide association identifies a single major locus contributing to survival into old age: the locus revisited. Aging Cell (in press). 

Devlin, B. and Roeder, K. Genomic control for association studies. Biometrics. 

Esparza-Gordillo, J., Weidinger, S., Folster-Holst, R., Bauerfeind, A., Ruschendorf, F., Schreiber, S., Franke, A., Vogler, R., Heath, S., Baurecht, H., Novak, N., Illig, T., Lee-Kirsch, M.A., Ciechanowicz, A., Kurek, M. and Piskackova T.M. A common variant on chromosome q associated with atopic dermatitis. Nat. Genet.

Nebel A., Anselmi C.V., Malovini A., Roncarati R., Novelli V., Villa F., Condorelli G.,
Bellazzi R. and Puca A.A. (2009) Association of the FOXO3A locus with extreme longevity in a southern Italian centenarian study.

A previous meta-analysis of four prospective cohort studies revealed a statistically significant and replicated association of rs9664222 with longevity (defined as reaching 90 years and older) (Newman et al. 2010). This SNP did not show any association in our large case-control samples (P = 0.611). This CCA result could be due to the different designs and/or levels of statistical power of the two studies. Moreover, we also tested the 33 polymorphisms from Sebastiani et al. (in press) in our imputed GWAS dataset, of which SNP rs2075650 that is in LD with the known APOE alleles (Sebastiani et al., in press) showed a significant association in our German sample. Also, the Dutch GWAS identified an APOE-related SNP as the most relevant marker with a deleterious effect on survival into old age. No other major longevity locus was found (Deelen et al., in press). Thus, our study and the independent Dutch study (Deelen et al., in press) both strengthen the conclusion that APOE is a very important genetic factor, and it may very well be the most relevant one influencing human longevity.

In summary, the GWAS carried out in our study revealed apart from APOE no novel candidate genes for longevity in humans. Larger samples, a more specific and genetically enriched longevity phenotype (so-called super-centenarians), or a meta-analysis involving several thousands of participants may be required to successfully and reliably identify additional genes through a GWAS. In addition, some genetic factors involved in longevity could not be detected in the present study on principal grounds, including low-frequency polymorphisms, copy-number variations, or epigenetic changes. Furthermore, it is noteworthy that although individual-specific mechanisms may be important for longevity, our study only considers probabilities on a population level. In the future, a genome-wide pathway-based approach (Chen et al., 2009; Luo et al., 2010) could be a useful means to explore the vascular genetic factors and human longevity.

Marciante K.D., Massaro J.M., Miljkovic I., Nalls M.A., Hernandez D., Uh H.W., Uitterlinden A.G., Vaupel J.W., Walston J., Westendorp R.G., Lumley T., van Duijn C.M., and Murabito J.M. A meta-analysis of genome-wide association studies of survival to age 90 years or older: Cohorts for Heart and Aging Research in Genomic Epidemiology J. Gerontol. A Biol. Sci. Med. Sci.

Pawlikowska L., Hu D., Huntsman S., Sung A., Chu C., Chen J., Joyner N.J., Hsueh W.C., Reiner A.P., Psaty B.M., Atzmon G., Barzilai N., Ziv E. and Browner W.S. Association of common variation in the insulin/IGF signaling pathway with human longevity. Cell.

Sklar P., de Bakker P.I.W., Daly M.J. and Sham P.C. PLINK: a tool set for genome association and population-based linkage analyses. Am. J. Hum.

R Development Core Team (2011) R: A language and Environment forSorry, but there is no text enclosed in ``` ```. Please provide the text for me to proofread and improve.Karasik, D., Benjamin, E.J., Guo, C.Y., Govindaraju, R., Kiel, D.P., Kelly-Hayes, M., Massaro, J.M., Pencina, M.J., Seshadri, S., Murabito, J.M. Genetic correlates of longevity and selected age-related phenotypes: a genome-wide association study in the Framingham Study. BMC Med. Genet. (Suppl.), S.