Separating within and between effects in family studies: an application to the study of blood pressure in children

In epidemiology the analyses of family or twin studies do not always fully exploit the data, as information on differences between siblings is often used while between-families effect are not considered. We show how cross-sectional time-series linear regression analysis can be easily implemented to estimate within- and between-families effects simultaneously and how these effects can then be compared using the Hausman test. We illustrate this approach with data from the Uppsala family study on blood pressure in children with age ranging from 5.5 to 12.3 years for the younger and from 7.5 to 13.8 years for the older siblings. Comparing the effect of differences in birth weight on blood pressure within-family (in full siblings) and between-families (in unrelated children) allows us to study the contributions of fixed and pregnancy-specific maternal effects on birth weight and consequently on blood pressure. Our data showed a 0.88 mmHg decrease (95 per cent confidence interval: -1.7 to -0.03 mmHg) in systolic blood pressure for one standard deviation increase in birth weight between siblings within a family and 0.88 mmHg (95 per cent confidence interval: -1.6 to -0.2 mmHg) decrease in systolic blood pressure for one standard deviation increase in birth weight between unrelated children. These estimates were controlled for sex, age, pubertal stage, body size and pulse rate of the children at examination and for maternal body size and systolic blood pressure. The within- and between-families effects were not significantly different, p = 0.19, suggesting that fixed and pregnancy-specific factors have similar effects on childhood systolic blood pressure.