;

:

–

Dawber TR, Meadors GF, Moore FE. Epidemiological ap- proaches to heart disease: The Framingham Study. Am J Public Health

;

:

–

Kannel WB, Feinleib M, M

amara PM, et al. An investi- gation of coronary heart disease in families: The Framing- ham offspring study. Am J Epidemiol

;

:

–

Splansky GL, Corey D, Yang Q, et al. The third generation cohort of the national heart, lung, and blood institute’s Framingham Heart Study: Design, recruitment, and initial examination. Am J Epidemiol

;

:

–

Rea SL, Wu DQ, Cypser JR, et al. A stress-sensitive reporter predicts longevity in isogenic populations of Caenorhabditis elegans. Nat Genet

;

:

–

Levine AJ, Feng ZH, Mak TW, et al. Coordination and communication between the p

and IGF-

-AKT-TOR signal transduction pathways. Genes Dev

;

:

–

Ukraintseva SV, Arbeev KG, Akushevich I, et al. Trade-offs between cancer and other diseases: Do they exist and in- fluence longevity? Rejuvenation Res

;

:

–

Seshadri S, D

tefano AL, Au R, et al. Genetic correlates of brain aging on MRI and cognitive test measures: a genome- wide association and linkage analysis in the Framingham study. BMC Med. Genet

;

Walter S, Atzmon G, Demerath EW, et al. A genome-wide association study of aging. Neurobiol Aging

;

:

.e

–

,e

Hong S-E, Heo H-S, Kim DH, et al. Revealing system-level correlations between aging and calorie restriction using a mouse transcriptome. Age

;

:

–

Seluanov A, Hine C, Azpurua J, et al. Hypersensitivity to contact inhibition provides a clue to cancer resistance of naked mole-rat. Proc Natl Acad Sci USA

;

:

–

Miotto E, Sabbioni S, Veronese A, et al. Frequent aberrant methylation of the CDH

gene-promoter in human colo- rectal and gastric cancer. Cancer Res

;

:

–

Finch CE. The neurobiology of middle-age has arrived. Neurobiol Aging

;

:

–

Ukraintseva SV, Yashin AI. Individual aging and cancer risk: How are they related? Demographic Res

;

:

–

van Heemst D, Mooijaart SP, Beekman M, et al. Variation in the human TP

gene affects old age survival and cancer mortality. Exp Gerontol

;

:

–

Orsted DD, Bojesen SE, Tybjaerg-Hansen A, Nordestgaard BG. Tumor suppressor p

Arg

Pro polymorphism and longevity, cancer survival, and risk of cancer in the general population. J Exp Med

;

:

–

Boquoi A, Chen T, Enders GH. Chemoprevention of mouse intestinal tumorigenesis by the cyclin-dependent kinase in- hibitor SNS-

Cancer Prev Res

;

:

–

Fornage M, Debette S, Bis JC, et al. Genome-wide association studies of cerebral white matter lesion burden: The CHARGE Consortium. Ann Neurol

;

:

–

O’Seaghdha CM, Yang Q, Glazer NL, et al. Common vari- ants in the calcium-sensing receptor gene are associated with total serum calcium levels. Hum Mol Genet

;

:

–

Nebel A, Kleindorp R, Caliebe A, et al. A genome-wide as- sociation study confirms APOE as the major gene influenc- ing survival in long-lived individuals. Mech Ageing Dev

;

:

–

The next logical steps in studying the genetic influence on longevity could deal with analyses of genetic mechanisms underlying complex relationships among physiological ag- ing changes, onsets of major diseases, and life span, taking into account the effects of both individual genes and poly- genic influence (additive and nonadditive) on these traits, as well as the impact of nongenetic factors.

Acknowledgments

The FHS project is conducted and supported by the Na- tional Heart, Lung, and Blood Institute (NHLBI) in collabo- ration with Boston University (N01 HC25195). The FHS data used for the analyses were obtained through dbGaP (phs000007.v3.p2). The authors acknowledge the investiga- tors that contributed the phenotype and genotype data for this study. This manuscript was not prepared in collabora- tion with investigators of the FHS and does not necessarily reflect the opinions or views of the FHS, Boston University, or the NHLBI. This work was partly supported by NIH/NIA grant R01AG030612.

Author Disclosure Statement

No competing financial interests exist.

References

Yang J, Benyamin B, M

voy BP, et al. Common SNPs plain a large proportion of the heritability for human Nat Genet

;

:

–

Peterson RE, Maes HH, Holmans P, et al. Genetic risk score comprised of common polygenic variation is ated with body mass index. Hum Genet

;

:

–

Allen HL, Estrada K, Lettre G, et al. Hundreds of clustered in genomic loci and biological pathways human height. Nature

;

:

–

Lunetta KL, D’Agostino RB, Sr., Karasik D, et al. correlates of longevity and selected age-related A genome-wide association study in the Framingham BMC Med Genet

;

(Suppl

):S

Hardy J, Singleton A. Genomewide association studies human disease. New Engl J Med

;

:

–

Newman AB, Walter S, Lunetta KL, et al. A meta-analysis four genome-wide association studies of survival to age years or older: The cohorts for heart and aging research Genomic Epidemiology Consortium. J Gerontol A Biol Med Sci

;

:

–

Malovini A, Illario M, Iaccarino G, et al. Association on long-living Individuals from Southern Italy rs

in the CAMKIV gene that regulates proteins. Rejuvenation Res

;

:

–

Manolio TA, Collins FS, Cox NJ, et al. Finding the heritability of complex diseases. Nature

;

:

–

Purcell SM, Wray NR, Stone JL, et al. Common variation contributes to risk of schizophrenia and disorder. Nature

;

:

–

murine hepatocellular carcinomas. Mol Cancer Res

;

:

–

Preuschhof C, Heekeren HR, Li S-C, et al. KIBRA and CLSTN

polymorphisms exert interactive effects on human episodic memory. Neuropsychologia

;

:

–

Jacobsen LK, Picciotto MR, Heath CJ, et al. Allelic variation of calsyntenin

(CLSTN

) modulates the impact of devel- opmental tobacco smoke exposure on mnemonic processing in adolescents. Biol Psychiatry

;

:

–

Liu F, Arias-Vasquez A, Sleegers K, et al. A genomewide screen for late-onset Alzheimer disease in a genetically iso- lated Dutch population. Am J Hum Genet

;

:

–