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Nonparametric linkage data for Previous subgroup. Found at: doi:

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Nonparametric linkage data for New subgroup. Found at: doi:

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Nonparametric linkage data for MC subgroup. Found at: doi:

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Nonparametric linkage data for FO subgroup. Found at: doi:

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Supplemental discussion. Found at: doi:

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Supporting Information

Table S1 Subject characteristics by age category for four subgroups, plus parametric analysis settings. Age, gender, and sibship composition statistics for the Previous, New, MC, and FO subgroups, plus parametric linkage parameters for all groups, are given across ten categories defined by gender-specific minimum requirements for expected age at death. The designations 2-ship, 3-ship, 4-ship, and 5-ship refer to sibships with two, three, four, or five siblings, respectively. Found at: doi:10.1371/journal.pone.0012432.s001 (0.14 MB DOC)

Acknowledgments

We thank Stephanie Brewster, Stevan Obradovic, Stacy Andersen, and Thomas Perls for providing DNA samples and phenotype information, and Eric Boyden, Lynn Boyden, and Karen Mowrer for helpful discussions and critical reading of the manuscript.

Author Contributions

Conceived and designed the experiments: SEB LMK. Performed the experiments: SEB. Analyzed the data: SEB. Wrote the paper: SEB LMK.

References

Pawlikowska L, Hu D, Huntsman S, Sung A, Chu C, et al. (

) Association of common genetic variation in the insulin/IGF

signaling pathway with human longevity. Aging Cell

:

–

Li Y, Wang WJ, Cao H, Lu J, Wu C, et al. (

) Genetic association of FOXO

A and FOXO

A with longevity trait in Han Chinese populations. Hum Mol Genet.

Cournil A, Kirkwood TB (

) If you would live long, choose your parents well. Trends Genet

:

–

Hjelmborg Jv, Iachine I, Skytthe A, Vaupel JW, M

ue M, et al. (

) Genetic influence on human lifespan and longevity. Hum Genet

:

–

Perls TT, Wilmoth J, Levenson R, Drinkwater M, Cohen M, et al. (

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

:

–

Gudmundsson H, Gudbjartsson DF, Frigge M, Gulcher JR, Stefansson K (

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

:

–

Kerber RA, O’Brien E, Smith KR, Cawthon RM (

) Familial excess longevity in Utah genealogies. J Gerontol A Biol Sci Med Sci

: B

–

Puca AA, Daly MJ, Brewster SJ, Matise TC, Barrett J, et al. (

) A genome- wide scan for linkage to human exceptional longevity identifies a locus on chromosome

Proc Natl Acad Sci U S A

:

–

Reed T, Dick DM, Uniacke SK, Foroud T, Nichols WC (

) Genome-wide scan for a healthy aging phenotype provides support for a locus near D

S

promoting healthy aging. J Gerontol A Biol Sci Med Sci

:

–

Beekman M, Blauw GJ, Houwing-Duistermaat JJ, Brandt BW, Westendorp RG, et al. (

) Chromosome

q

, microsomal transfer protein gene, and human longevity: novel data and a meta-analysis of association studies. J Gerontol A Biol Sci Med Sci

:

–

Karasik D, Hannan MT, Cupples LA, Felson DT, Kiel DP (

) Genetic contribution to biological aging: the Framingham Study. J Gerontol A Biol Sci Med Sci

:

–

Geesaman BJ, Benson E, Brewster SJ, Kunkel LM, Blanche H, et al. (

) Haplotype-basedidentificationofamicrosomal transferproteinmarkerassociated with the human lifespan. Proc Natl Acad Sci U S A

:

–

Wang T, Elston RC (

) The bias introduced by population stratification in IBD based linkage analysis. Hum Hered

:

–

Bell FC, Miller ML (

) Life Tables for the United States Social Security Area

–

U.S. Social Security Administration. Available: http://www.ssa. gov/OACT/NOTES/as

/TOC.html. Accessed

Abecasis GR, Cherny SS, Cookson WO, Cardon LR (

) Merlin—rapid analysis of dense genetic maps using sparse gene flow trees. Nat Genet

:

–

Biodemographic trajectories of longevity. Science

:

–

Vaupel JW, Manton KG, Stallard E (

) The impact of heterogeneity individual frailty on the dynamics of mortality. Demography

:

–

Vaupel JW, Yashin AI (

) Heterogeneity’s ruses: some surprising effects selection on population dynamics. Am Stat

:

–

Hitt R, Young-Xu Y, Silver M, Perls T (

) Centenarians: the older you the healthier you have been. Lancet

:

Fries JF (

) Aging, natural death, and the compression of N Engl J Med

:

–

Browner WS, Kahn AJ, Ziv E, Reiner AP, Oshima J, et al. (

) The of human longevity. Am J Med

:

–

Christensen K, Johnson TE, Vaupel JW (

) The quest for determinants of human longevity: challenges and insights. Nat Rev Genet

–

Martin GM, Bergman A, Barzilai N (

) Genetic determinants of health span and life span: progress and new opportunities. PL

Genet

:

Davignon J, Bouthillier D, Nestruck AC, Sing CF (

) Apolipoprotein polymorphism and atherosclerosis: insight from a study in octogenarians. Am Clin Climatol Assoc

:

–

Schachter F, Faure-Delanef L, Guenot F, Rouger H, Froguel P, et al. Genetic associations with human longevity at the APOE and ACE loci. Genet

:

–

Lewis SJ, Brunner EJ (

) Methodological problems in genetic studies of longevity—the apolipoprotein E gene as an example. Int J

:

–

Novelli V, Viviani Anselmi C, Roncarati R, Guffanti G, Malovini A, et al. Lack of replication of genetic associations with human longevity.

:

–

Kuningas M, Magi R, Westendorp RG, Slagboom PE, Remm M, et al. Haplotypes in the human Foxo

a and Foxo

a genes; impact on disease mortality at old age. Eur J Hum Genet

:

–

Willcox BJ, Donlon TA, He Q, Chen R, Grove JS, et al. (

) genotype is strongly associated with human longevity. Proc Natl Acad Sci U S

:

–

Flachsbart F, Caliebe A, Kleindorp R, Blanche H, von Eller-Eberstein H, et (

) Association of FOXO

A variation with human longevity confirmed German centenarians. Proc Natl Acad Sci U S A

:

–