,

e

Barrett, J.C.,

Haploview: visualization and analysis of SNP genotype data. Cold Spring Harb. Protoc.

pdb.ip

Barrett, J.C., Fry, B., Maller, J., Daly, M.J.,

Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics

,

e

Davignon, J., Gregg, R.E., Sing, C.F.,

Apolipoprotein E polymorphism and atherosclerosis. Arteriosclerosis

,

e

De Benedictis, G., Tan, Q., Jeune, B., Christensen, K., Ukraintseva, S.V., Bonafe, M., Franceschi, C., Vaupel, J.W., Yashin, A.I.,

Recent advances in human gene- longevity association studies. Mech. Ageing Dev.

,

e

Deelen, J., Beekman, M., Uh, H.W., Helmer, Q., Kuningas, M., Christiansen, L., Kremer, D., van der Breggen, R., Suchiman, H.E., Lakenberg, N., van den Akker, E.B., Passtoors, W.M., Tiemeier, H., van Heemst, D., de Craen, A.J., Rivadeneira, F., de Geus, E.J., Perola, M., van der Ouderaa, F.J., Gunn, D.A., Boomsma, D.I., Uitterlinden, A.G., Christensen, K., van Duijn, C.M., Heijmans, B.T., Houwing-Duistermaat, J.J., Westendorp, R.G., Slagboom, P.E.,

Genome- wide association study identifies a single major locus contributing to survival into old age; the APOE locus revisited. Aging Cell

,

e

Ewbank, D.C.,

Mortality differences by APOE genotype estimated from demographic synthesis. Genet. Epidemiol.

,

e

Ewbank, D.C.,

Differences in the association between apolipoprotein E genotype and mortality across populations. J. Gerontol. A Biol. Sci. Med. Sci.

,

e

Finch, C.E., Tanzi, R.E.,

Genetics of aging. Science

,

e

Galinsky, D., Tysoe, C., Brayne, C.E., Easton, D.F., Huppert, F.A., Dening, T.R., Paykel, E.S., Rubinsztein, D.C.,

Analysis of the apo E/apo C-I, angiotensin converting enzyme and methylenetetrahydrofolate reductase genes as candi- dates affecting human longevity. Atherosclerosis

,

e

Gudmundsson, H., Gudbjartsson, D.F., Frigge, M., Gulcher, J.R., Stefansson, K.,

Inheritance of human longevity in Iceland. Eur. J. Hum. Genet.

,

e

Herskind, A.M., M

ue, M., Holm, N.V., Sorensen, T.I., Harvald, B., Vaupel, J.W.,

The heritability of human longevity: a population-based study of

Danish twin pairs born

-

Hum. Genet.

,

e

Bader, G., Zuliani, G., Kostner, G.M., Fellin, R.,1998. Apolipoprotein E is not associated with longevity or disability in a sample of Italian octo-

We also found that the frequency and likelihood of carrying a G allele in rs2075650 of TOMM40 was lower among offspring in the LLFS, compared with the likelihood in married-in controls. Recent genome wide association studies in German, Dutch, Danish, and US Caucasian cohorts of long-lived individuals identified rs2075650 in TOMM40 as associated with longevity (Deelen et al., 2011 ; Nebel et al., 2011; Sebastiani et al., 2012), but also close to and in linkage disequilibrium with the rs429358, the APOE ε4 allele, and the investigators suggested that rs2075650 might not have an independent effect on longevity. Consistent with these analyses, we found that the addition of the ε4 allele to our models attenuated the association between offspring and the likelihood of carrying the G allele. When the analysis was restricted to those with the APOE ε3/ ε3 genotype, the association of offspring with the likelihood of carrying the G allele was not attenuated, but failed to reach statistical significance. Replication of this association in other long- lived cohorts will be needed to elucidate these results.

A.M., McGue, M., Holm, N.V., Sorensen, T.I., Harvald, B., Vaupel, J.W.,1996. The heritability of human longevity: a population-based study of 2872 Danish twin pairs born 1870-1900. Hum. Genet. 97, 319e323.

The limitations of the study include relatively small sample sizes and restriction of the analysis to Caucasians. It would be of interest

N. Schupf et al. / Neurobiology of Aging 34 (2013) 1287e1291

Mitchell, B.D., Hsueh, W.C., King, T.M., Pollin, T.I., Sorkin, J., Agarwala, R., Schaffer, A.A., Shuldiner, A.R.,

Heritability of life span in the Old Order Amish. Am. J. Med. Genet.

,

e

Nebel, A., Kleindorp, R., Caliebe, A., Nothnagel, M., Blanche, H., Junge, O., Wittig, M., Ellinghaus, D., Flachsbart, F., Wichmann, H.E., Meitinger, T., Nikolaus, S., Franke, A., Krawczak, M., Lathrop, M., Schreiber, S.,

A genome-wide association study confirms APOE as the major gene influencing survival in long- lived individuals. Mech. Ageing Dev.

,

e

Pedersen, C.B., Gotzsche, H., Moller, J.O., Mortensen, P.B.,

The Danish Civil Registratio

ystem.Acohortofeightmillionpersons.Dan.Med.Bull.

,

e

Perls, T.T., Wilmoth, J., Levenson, R., Drinkwater, M., Cohen, M., Bogan, H., Joyce, E., Brewster, S., Kunkel, L., Puca, A.,

Life-long sustained mortality advantage of siblings of centenarians. Proc. Natl. Acad. Sci. U. S. A.

,

e

Rebeck, G.W., Perls, T.T., West, H.L., Sodhi, P., Lipsitz, L.A., Hyman, B.T.,

Reduced apolipoprotein epsilon

allele frequency in the oldest old Alzheimer’s patients and cognitively normal individuals. Neurology

,

e

Schachter, F., Faure-Delanef, L., Guenot, F., Rouger, H., Froguel, P., Lesueur-Ginot, L., Cohen, D.,

Genetic associations with human longevity at the APOE and ACE loci. Nat. Genet.

,

e

Sebastiani, P., Hadley, E.C., Province, M., Christensen, K., Rossi, W., Perls, T.T., Ash, A.S.,

A family longevity selection score: ranking sibships by their longevity, size, and availability for study. Am. J. Epidemiol.

,

e

Sebastiani, P., Solovieff, N., Dewan, A.T., Walsh, K.M., Puca, A., Hartley, S.W., Melista, E., Andersen, S., Dworkis, D.A., Wilk, J.B., Myers, R.H., Steinberg, M.H., Montano, M., Baldwin, C.T., Hoh, J., Perls, T.T.,

Genetic signatures of exceptional longevity in humans. PL

One

, e