A meta-analysis of genome-wide association studies identifies multiple longevity genes

Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a rigorous longevity phenotype definition including 11,262/3484 cases surviving at or beyond the age corresponding to the 90th/99th survival percentile, respectively, and 25,483 controls whose age at death or at last contact was at or below the age corresponding to the 60th survival percentile. Consistent with previous reports, rs429358 (apolipoprotein E (ApoE) ε4) is associated with lower odds of surviving to the 90th and 99th percentile age, while rs7412 (ApoE ε2) shows the opposite. Moreover, rs7676745, located near GPR78, associates with lower odds of surviving to the 90th percentile age. Gene-level association analysis reveals a role for tissue-specific expression of multiple genes in longevity. Finally, genetic correlation of the longevity GWA results with that of several disease-related phenotypes points to a shared genetic architecture between health and longevity

Unobserved heterogeneity in hazard rate models: a test and an illustration from a study of career mobility

This paper proposes a test for neglected heterogeneity in continuous-time hazard rate models that can be done easily using generally available program packages. It is a score test appropriate for cases in which the variance of the heterogeneity is small and it can be applied quite generally, provided that the generalized residuals can be calculated. The test is demonstrated using data on the career trajectories of German males from the German Life History Study

Competitive response to radical product innovations

Radical product innovations are often agents of creative destruction. They threaten to destroy existing market positions, and yet they often yield vast new market opportunities. This article examines how competitors respond to the introduction of radical product innovations. The authors argue that competitive response to radical product innovations is inherently different from response to the incremental innovations that are typically studied in existing research. They introduce the dual concepts of market expansion and entry thresholds to develop new hypotheses about competitive response. Some of these hypotheses contradict prior literature. Using objective data from the U.S. pharmaceutical industry between 1997 and 2001, they estimate a shared-frailty hazard model to explain the competitive response to radical product innovations. The results show that the likelihood of competitive response is substantially higher when the introducing firm is large or market dependent. Moreover, the response is highest when the innovation is introduced in a small market by a large firm. These results contradict those from much prior research on competitive response to product innovation