Increasing Sibling Relative Risk of Survival to Older and Older Ages and the Importance of Precise Definitions of "Aging," "Life Span," and "Longevity"

Abstract

The lack of a formal definition of human longevity continues to generate confusion about its genetic and nongenetic determinants. In order to characterize how differences in birth year cohorts and percentiles of survival are associated with familial contribution to variation in survival, we estimated sibling relative risk of living to increasingly rare percentiles of survival based on a dataset of 1,917 validated sibships each containing at least one individual living to age 90 years. About 1,042 of the sibships included at least one individual who survived to age 100 and 511 included at least one individual who survived to age 105 and older. We show that sibling relative risk increases with older ages, sex, and earlier birth year cohorts of the proband and siblings of male 90-year-olds (5th percentile of survival) have 1.73 (95% CI: 1.5; 2.0) times the chance of living to age 90, while siblings of both male and female probands who survived to age 105 years (~0.01 percentile of survival) have 35.6 (95%CI: 15.1; 67.7) times the chance of living to age 105 compared with population controls. These results emphasize the importance of consistently defining the longevity phenotype in terms of rarity of survival for appropriate comparisons across studies.

Keywords: Centenarian; Demographic selection; Heritability; Longevity; Sibling relative risk..

Figure 1.

Posterior density of the parameter representing the sex effect, for ages A = 90, 95, 100, and 105. The increasing symmetry of the posterior distribution for older ages suggests that sex of the longest lived sibling does not affect the chance of living to very old ages of the siblings.

Figure 2.

Top panel: estimated conditional probability (left panel, solid lines) and relative risk (right panel, solid lines) and 95% credible interval (dashed lines) that an individual survived to age A, given that the longest lived sibling (proband) survived to age A* and was born in the 1900 birth year cohort. Black: age A = 90, red: age A = 95, green: age A = 100. The U.S. 1900 cohort life table was used to estimate the population risk of living to ages 90, 95, and 100 for the generation of the top panels. Dots in the left panels represent the conditional probabilities estimated from the observed frequencies. Bottom panel: Conditional probabilities and estimated relative risks for siblings born in the 1890 birth year cohort. The Swedish 1890–1899 cohort life table was used to estimate the population risk of living to ages 90, 95, and 100. The increased conditional probability combined with the greater rarity of centenarians in the 1890 Swedish birth cohort life table (www.lifetable.de) results in very large sibling relative risks.