Historical and social contexts are important to the educatio

Historical and social contexts are important to the education-mortality association (Hayward, Hummer & Sasson, 2015), and the family influence on this relationship may also be context dependent. As a consequence, the interplay between family, education, and health outcomes may change over time. However, the present study averages across a wide range of birth cohorts, age groups, and time periods. During the twentieth century, the educational system became more comprehensive, and upper-secondary and tertiary education expanded substantially (Jonsson and Mills, 1993). Thus, all else equal, a younger sibling is more likely to attain a higher educational level than an older sibling. Assuming that a causal effect of education on health is present, changes in the educational system may generate a difference in siblings’ life expectancy. However, if the education-mortality association is mainly confounded by other factors, e.g., familial circumstances, health and mortality differences between siblings would not be affected by educational expansion. Further, there is a negative effect of birth order on educational attainment but the educational expansion may counteract this effect (cf. Barclay, 2015), particularly in large Exendin-4 in which the age gap between the first and last child is substantive. As a robustness check, we tested whether our results were substantially changed when we restricted our all-cause mortality analyses to sibling groups with a maximum age gap of four years. The results of these restricted analyses are nearly identical to the estimates based on all sibling groups, which suggests that a large age gap between some sibling groups is not driving the results. We have briefly outlined the statistical problems with interpreting the attenuation in education-mortality association between the population-based and family-based estimates. Because of the problem of the non-collapsibility of the HR, the associations within families may inflate even in the absence of confounding. The most attractive solution to this problem is Aalen\'s additive survival model where the subgroup and population-averaged associations are the same (Martinussen & Vansteelandt, 2013), but work is needed to implement a solution in software that works with covariates with very high degrees of freedom such as family of origin in the present study. We want to stress that the educational gradient in mortality between siblings must be interpreted with caution. Despite earlier enthusiasm (McGue, Osler & Christensen, 2010; Rutter, 2007), it is clear that sibling comparisons do not mimic experiments that are characterized by exogenous variation in exposure. Sibling comparisons are a form of imperfect matching, and they come at the dual loss of precision (which may be less important in the context of this study) and bias away from the causal effect of education. One source of bias might arise from the fact that families in which all siblings have the same education are informative for the population as a whole, but uninformative for the between sibling analyses. For example, it is an open (but unanswerable) question if the unobservable educational gradient in siblings in families who are ‘doomed’ to low education can be inferred from the educational gradient in families in which the siblings actually have different educations. Using the association between the sexes of siblings as an example, we have also demonstrated empirically that restriction to discordant pairs will induce non-causal association that will bias the estimates away from the causal effect of education. This should be taken into account when interpreting the findings for causes of death, where the underlying conditions are likely to affect educational success and mortality, for example schizophrenia in the analyses of education and risk of suicide (Agerbo, Byrne, Eaton & Mortensen, 2004). Because the familial clustering of education is very strong, the potential for bias is considerable: Having an education that is different from one\'s siblings is likely to have a reason. It may be possible to obtain an idea of the directionality of the bias. In general, we would expect the bias induced by design to work to increase the educational gradient in mortality because we believe that the majority of factors that limit educational success are likely to be detrimental to health if they have any effect on health at all. In theory one might imagine other scenarios: Devoting one\'s time to sport activities might impede the chances of obtaining a long education while having a positive effect on health, or, for example, a sibling may have been encouraged to obtain a long education because it was felt that he or she was too frail for a manual job. However, we believe that the net result across families is likely to result in bias away from the null, but this assumption is contingent on the context-specific distribution of all contributory factors according to education and familial background, which is obviously not something that is easily documented.